Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients

Abstract

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

https://ift.tt/2JbAfZy

GNAS-mutated carcinoma arising from gastric foveolar metaplasia in the duodenum after 9 years of observation

Abstract

This case involved an 80-year-old man. Screening with esophagogastroduodenoscopy (EGD) in 2004 revealed Brunner's gland hyperplasia (BGH), 5 mm in size, in the duodenal bulb. The size of the lesion increased and its shape has changed since then, as detected in subsequent EGDs. The lesion had increased in size to 15 mm with a depression and biopsy specimens revealed an adenocarcinoma. The patient underwent endoscopic mucosal resection. Histopathological assessments indicated an adenocarcinoma arising from gastric foveolar metaplasia (GFM) adjacent to BGH. BGH stained positive for MUC6, and GFM and the adenocarcinoma stained positive for MUC5AC. Mutations of the GNAS gene were not detected in the GFM biopsied in 2007. On the other hand, common GNAS mutations (R201H) were detected in GFM and the adenocarcinoma in the endoscopically resected specimen in 2013. Moreover, mutant allele frequencies were higher in the carcinoma than in GFM. The patient remains disease-free for 4 years after endoscopic treatment. This case report further supports the notion that GFM may be a precursor lesion in the process of GNAS-mutated, gastric-type duodenal carcinogenesis.

https://ift.tt/2GZF47f

Robotic kidney autotransplantation in a porcine model: a procedure-specific training platform for the simulation of robotic intracorporeal vascular anastomosis

Abstract

Robotic-assisted kidney transplantation (RKT) with the Da Vinci (Intuitive, USA) platform has been recently developed to improve outcomes by decreasing surgical site complications and morbidity, especially in obese patients. This potential paradigm shift in the surgical technique of kidney transplantation is performed in only a few centers. For wider adoption of this high stake complex operation, we aimed to develop a procedure-specific simulation platform in a porcine model for the training of robotic intracorporeal vascular anastomosis and evaluating vascular anastomoses patency. This paper describes the requirements and steps developed for the above training purpose. Over a series of four animal ethics' approved experiments, the technique of robotic-assisted laparoscopic autotransplantation of the kidney was developed in Amsterdam live pigs (60–70 kg). The surgery was based around the vascular anastomosis technique described by Menon et al. This non-survival porcine training model is targeted at transplant surgeons with robotic surgery experience. Under general anesthesia, each pig was placed in lateral decubitus position with the placement of one robotic camera port, two robotic 8 mm ports and one assistant port. Robotic docking over the pig posteriorly was performed. The training platform involved the following procedural steps. First, ipsilateral iliac vessel dissection was performed. Second, robotic-assisted laparoscopic donor nephrectomy was performed with in situ perfusion of the kidney with cold Hartmann's solution prior to complete division of the hilar vessels, ureter and kidney mobilization. Thirdly, the kidney was either kept in situ for orthotopic autotransplantation or mobilized to the pelvis and orientated for the vascular anastomosis, which was performed end to end or end to side after vessel loop clamping of the iliac vessels, respectively, using 6/0 Gore-Tex sutures. Following autotransplantation and release of vessel loops, perfusion of the graft was assessed using intraoperative indocyanine green imaging and monitoring urine output after unclamping. This training platform demonstrates adequate face and content validity. With practice, arterial anastomotic time could be improved, showing its construct validity. This porcine training model can be useful in providing training for robotic intracorporeal vascular anastomosis and may facilitate confident translation into a transplant human recipient.

https://ift.tt/2pUS07a

Pathophysiology of Noncardiac Syncope in Athletes

Abstract

The most frequent cause of syncope in young athletes is noncardiac etiology. The mechanism of noncardiac syncope (NCS) in young athletes is neurally-mediated (reflex). NCS in athletes usually occurs either as orthostasis-induced, due to a gravity-mediated reduced venous return to the heart, or in the context of exercise. Exercise-related NCS typically occurs after the cessation of an exercise bout, while syncope occurring during exercise is highly indicative of the existence of a cardiac disorder. Postexercise NCS appears to result from hypotension due to impaired postexercise vasoconstriction, as well as from hypocapnia. The mechanisms of postexercise hypotension can be divided into obligatory (which are always present and include sympathoinhibition, histaminergic vasodilation, and downregulation of cardiovagal baroreflex) and situational (which include dehydration, hyperthermia and gravitational stress). Regarding postexercise hypocapnia, both hyperventilation during recovery from exercise and orthostasis-induced hypocapnia when recovery occurs in an upright posture can produce postexercise cerebral vasoconstriction. Athletes have been shown to exhibit differential orthostatic responses compared with nonathletes, involving augmented stroke volume and increased peripheral vasodilation in the former, with possibly lower propensity to orthostatic intolerance.

https://ift.tt/2pStYK4

Assessment of Skeletal Muscle Contractile Properties by Radial Displacement: The Case for Tensiomyography

Abstract

Skeletal muscle operates as a near-constant volume system; as such muscle shortening during contraction is transversely linked to radial deformation. Therefore, to assess contractile properties of skeletal muscle, radial displacement can be evoked and measured. Mechanomyography measures muscle radial displacement and during the last 20 years, tensiomyography has become the most commonly used and widely reported technique among the various methodologies of mechanomyography. Tensiomyography has been demonstrated to reliably measure peak radial displacement during evoked muscle twitch, as well as muscle twitch speed. A number of parameters can be extracted from the tensiomyography displacement/time curve and the most commonly used and reliable appear to be peak radial displacement and contraction time. The latter has been described as a valid non-invasive means of characterising skeletal muscle, based on fibre-type composition. Over recent years, applications of tensiomyography measurement within sport and exercise have appeared, with applications relating to injury, recovery and performance. Within the present review, we evaluate the perceived strengths and weaknesses of tensiomyography with regard to its efficacy within applied sports medicine settings. We also highlight future tensiomyography areas that require further investigation. Therefore, the purpose of this review is to critically examine the existing evidence surrounding tensiomyography as a tool within the field of sports medicine.

https://ift.tt/2E5B961

Foreword for the special issue on Neural Coding

https://ift.tt/2pPzlda

Empirical Functions for Conversion of Femur Areal and Volumetric Bone Mineral Density

Abstract

Bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) is areal and in the unit of g/cm², while BMD measured by quantitative computed tomography (QCT) is volumetric and in the unit of g/cm³. There is often a need to convert them to each other, but a simple conversion method is not available. The objective of this study was to establish empirical functions for the conversion. QCT of left femur from 67 subjects were acquired from a local clinical centre. For each subject, volumetric BMD was extracted from QCT using QCT Pro; the corresponding areal BMD was measured by CTXA-Hip. Both QCT Pro and CTXA-Hip are commercial software. The paired volumetric and areal BMD datasets were randomly split into two groups, and used respectively in construction and validation of empirical functions. Correlation between volumetric and areal BMD was 0.9073 (p < 0.0001) without considering femoral neck width (FNW), and 0.9970 (p < 0.0001) with the consideration of FNW. In the validations, the best agreement between predicted and measured volumetric BMD was R² = 0.9796, SSE = 0.0074, CV = 2.7%; the best agreement between predicted and measured areal BMD was R² = 0.9713, SSE = 0.0072, CV = 2.8%. Femur size represented by FNW had substantial effect on correlation between areal and volumetric BMD. With the consideration of FNW, areal and volumetric BMD can be converted to each other using the empirical functions constructed in this study.

https://ift.tt/2GnwTVp

Inferential Motion Reconstruction of Fall Accident Based on LSTM Neural Network

Abstract

With the rapid development of wearable technology, wearable medical devices have gradually garnered a significant amount of research interest. Motion reconstruction can accurately reproduce the posture of the user at the time of the accident, which provides medical personnel with necessary reference information. However, because of the vast range of human body activities, motion reconstruction needs high-frequency sampling data to avoid the occurrence of errors. Moreover, the fact that movements resulting from an accident can be irregular, the difficulties arising from unexpected training samples. This study attempts to establish a real-time human body inferential motion reconstruction system on fall accident. The data of human motion is recorded by using tri-axis accelerometers and tri-axis gyroscopes. The angles and tracks of the human limbs computed, and the next action occurrence point deduced using long short-term memory. Then the postural trajectory is corrected using feedback inference of gravity data from the end of a fall accident. Through the correction mechanism of bidirectional feedback, the error diffusion caused can reduce efficiency. In this study, using a parameter adjustment strategy under data sampling rate of 0.01 s, the average normal-m reconstruction rate, as well as the fall-motion reconstruction rate, can be determined. The overall posture is reproduced through the 3D video to ambulance personnel as a reference.

https://ift.tt/2Ii59y4

Electromagnetic radiation and behavioural response of ticks: an experimental test

Abstract

Factors associated with the increased usage of electronic devices, wireless technologies and mobile phones nowadays are present in increasing amounts in our environment. All living organisms are constantly affected by electromagnetic radiation which causes serious environmental pollution. The distribution and density of ticks in natural habitats is influenced by a complex of abiotic and biotic factors. Exposure to radio-frequency electromagnetic field (RF-EMF) constitutes a potential cause altering the presence and distribution of ticks in the environment. Our main objective was to determine the affinity of Dermacentor reticulatus ticks towards RF-EMF exposure. Originally designed and constructed radiation-shielded tube (RST) test was used to test the affinity of ticks under controlled laboratory conditions. All test were performed in an electromagnetic compatibility laboratory in an anechoic chamber. Ticks were irradiated using a Double-Ridged Waveguide Horn Antenna to RF-EMF at 900 and 5000 MHz, 0 MHz was used as control. The RF-EMF exposure to 900 MHz induced a higher concentration of ticks on irradiated arm of RST as opposed to the RF-EMF at 5000 MHz, which caused an escape of ticks to the shielded arm. This study represents the first experimental evidence of RF-EMF preference in D. reticulatus. The projection of obtained results to the natural environment could help assess the risk of tick borne diseases and could be a tool of preventive medicine.

https://ift.tt/2Gr3xl1

Phylogenetic insights on Mediterranean and Afrotropical Rhipicephalus species (Acari: Ixodida) based on mitochondrial DNA

Abstract

A multigene phylogeny including 24 Rhipicephalus species from the Afrotropical and Mediterranean regions, based on mitochondrial DNA genes (COI, 12S and 16S), was constructed based on Bayesian inference and maximum likelihood estimations. The phylogenetic reconstruction revealed 31 Rhipicephalus clades, which include the first molecular records of Rhipicephalus duttoni (Neumann), and Rhipicephalus senegalensis (Koch). Our results support the R. pulchellus, R. evertsi and R. pravus complexes as more phylogenetically close to Rhipicephalus (Boophilus) than to the remaining Rhipicephalus clades, suggesting two main monophyletic groups within the genus. Additionally, the phenotypic resembling R. sanguineus s.l. and Rhipicephalus turanicus (Pomerantsev) are here represented by nine clades, of which none of the R. turanicus assemblages appeared as distributed in the Iberian Peninsula. These results not only indicate that both species include more cryptic diversity than the already reported, but also suggest that R. turanicus distribution is less extended than previously anticipated. This analysis allowed to improve species identification by exposing cryptic species and reinforced mtDNA markers suitability for intra/inter-species clarification analyses. Incorporating new species molecular records to improve phylogenetic clarification can significantly improve ticks' identification methods which will have epidemiologic implications on public health.

https://ift.tt/2GnDn6O

Targeted Gene Deletion in Cordyceps militaris Using the Split-Marker Approach

Abstract

The macrofungus Cordyceps militaris contains many kinds of bioactive ingredients that are regulated by functional genes, but the functions of many genes in C. militaris are still unknown. In this study, to improve the frequency of homologous integration, a genetic transformation system based on a split-marker approach was developed for the first time in C. militaris to knock out a gene encoding a terpenoid synthase (Tns). The linear and split-marker deletion cassettes were constructed and introduced into C. militaris protoplasts by PEG-mediated transformation. The transformation of split-marker fragments resulted in a higher efficiency of targeted gene disruption than the transformation of linear deletion cassettes did. The color phenotype of the Tns gene deletion mutants was different from that of wild-type C. militaris. Moreover, a PEG-mediated protoplast transformation system was established, and stable genetic transformants were obtained. This method of targeted gene deletion represents an important tool for investigating the role of C. militaris genes.

https://ift.tt/2GYlmcf

Secukinumab Versus Adalimumab for Psoriatic Arthritis: Comparative Effectiveness up to 48 Weeks Using a Matching-Adjusted Indirect Comparison

Abstract

Introduction

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations.

Methods

Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted).

Results

After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032).

Conclusions

In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16–48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings.

Funding

Novartis Pharma AG.

https://ift.tt/2IjcoWD

Intrauterine arterial pseudoaneurysm, a rare cause of per vaginal bleeding

Abstract

The current study evaluated two cases of pervaginal bleeding subsequent of intrauterine arterial pseudoaneurysm. Each case was complaining of intermittent attacks of heavy vaginal bleeding: one case with history of cesarean section and the other case after uterine curettage. Intrauterine arterial pseudoaneurysm can be caused by a traumatic injury to the vessel wall with subsequent formation of periarterial hematoma that liquefies forming periarterial bloody cyst, which communicates through the narrow neck with the arterial lumen. Transvaginal ultrasound aided with color duplex capability is an accurate tool for assessment.

https://ift.tt/2uwW0Q2

Study of non-extensive entropy of bound polaron in monolayer graphene

Abstract

An electron is coupled to the longitudinal acoustic phonon on the surface of the graphene with Coulomb impurity has been considered. The ground state energy of the polaron has been obtained using the variational method. Tsallis entropy variations have been studied with magnetic field, temperature, Coulomb bound parameter and the charge for different substances such as SiC, HfO₂, h-BN, and SiO₂. It is found that the entropy increases with enhancing temperature and Coulomb bound parameter. But, it decreases with enhancing the charge. The entropy increases with decreasing the non-extensive parameter q for all substances at constant Coulomb bound parameter.

https://ift.tt/2GqRTGP

Testing a healthcare provider–patient communicative relationship quality model of pharmaceutical care in hospitals

Abstract

Background Patient-centeredness and participatory care is increasingly regarded as a proxy for high-quality interpersonal care. Considering the development of patient-centeredness and participatory care relationship model in pharmacist–patient domain, it is of great significance to explore the mechanism of how pharmacist and patient participative behaviors influence relationship quality and patient outcomes. Objective To validate pharmacist–patient relationship quality model in Chinese hospitals. Setting: Four tertiary hospitals in 2017. Methods The provision of pharmaceutical care was investigated. A cross-sectional questionnaire survey covering different constructs of communicative relationship quality model was conducted and the associations among pairs of the study constructs were explored. Based on the results of confirmatory factor analysis, path analysis was conducted to validate the proposed communicative relationship quality model. Main outcome measure Model fit indicators including Tucker–Lewis index (TLI), comparative fit index (CFI), root mean square error of approximation (RMSEA) and weighted root mean square residual(WRMR). Results There were 589 patients included in our study. The final path model had an excellent fit (TLI = 0.98, CFI = 0.98, RMSEA = 0.05; WRMR = 1.06). HCP participative behavior/patient-centeredness (β = 0.79, p < 0.001) and interpersonal communication (β = 0.13, p < 0.001) directly impact the communicative relationship quality. But patient participative behavior was not a predictor of either communicative relationship quality or patient satisfaction. Conclusion HCP participative behavior/patient-centeredness and interpersonal communication are positively related to relationship quality, and relationship quality is mediator between HCP participative behavior and interpersonal communication with patient satisfaction.

https://ift.tt/2uzW7KH

Quality pharmacy services and key performance indicators in Polish NICUs: a Delphi approach

Abstract

Background Currently, there is no literature describing what a quality level of practice entails in Polish neonatal intensive care units (NICUs), nor are there any means of currently measuring the quality of pharmaceutical care provided to NICU patients. Objective To identify a set of essential pharmacist roles and pharmacy-relevant key performance indicators (KPI's) suitable for Polish neonatal intensive units (NICUs). Setting Polish hospital pharmacies and NICUs. Method Using a modified Delphi technique, potential KPI's structured along Donabedian's domains as well as pharmacy services were presented to an expert panel of stakeholders. Two online, consecutive Delphi rounds, were completed by panellists between August and September 2017. Main outcome measure To identify the minimum level of pharmacy services that should be consistently provided to NICU patients. Results A total of 16 panellists contributed to the expert panel. Overall, consensus of 75% was reached for 23 indicators and for 28 roles. When considering pharmacy services for the NICU, the experts were found to highly value traditional pharmacy roles, such as dispensing and extemporaneous compounding, however, they were still eager for roles in the other domains, such as educational and clinical services, to be listed as essential for NICU practice. Panellists were found to positively value the list of indicators presented, and excluded only 9 out of the total list. Conclusion There is a need for future research to establish a minimum standard of practice for Polish pharmacists to encourage the progression and standardisation of hospital pharmacy services to meet the level of practice seen in NICUs worldwide.

https://ift.tt/2GENseV

Pharmacist supply of sildenafil: pharmacist’s experiences and perceptions on training and tools for supply

Abstract

Background In 2014, New Zealand reclassified sildenafil (for erectile dysfunction) to allow supply by specially trained pharmacists under strict criteria. Objective The study aimed to determine pharmacists' experiences and perspectives on the training for, and supply of sildenafil under this model. Setting New Zealand community pharmacy. Method This qualitative study captured data with a semi-structured interview used with purposively-sampled participants. A maximum variation sample was used to select a wide range of pharmacists working in various pharmacies, including pharmacists who were trained to provide sildenafil and those not trained to supply sildenafil. Consenting pharmacists were interviewed, with interviews audio-recorded and transcribed. Analysis used a framework approach. Main outcome measures Topics explored included: satisfaction and experience of the training; suitability and usability of the screening tools; experiences of the supply process and why some pharmacists chose not to become trained. Results Thirty-five pharmacists were interviewed. Training was seen as uncomplicated and the screening tools provided confidence that key consultation areas were covered. Most consultations reportedly took 15–20 min, some up to 60 min. Pharmacists reported being comfortable with the consultations. Many men requesting supply fell outside of the parameters, resulting in medical referral. This new model of supply was seen as a positive for pharmacists and their patients. Unaccredited pharmacists reported a perceived lack of interest from men, or ability to provide the service as reasons for not seeking accreditation. Conclusion New Zealand's model of pharmacist supply of sildenafil appears workable with some areas for improvement identified.

https://ift.tt/2Gl8W13

Impact of warfarin discharge education program on hospital readmission and treatment costs

Abstract

Background Although warfarin is highly effective, management of patients prescribed warfarin is complex due to its narrow therapeutic window. Objective To evaluate the impact of a formal warfarin discharge education program (WDEP) on hospital readmission and treatment costs in patients who received warfarin therapy. Setting Robert Wood Johnson University Hospital Somerset in Somerville, New Jersey, USA. Method In this interventional cohort study, patients were assigned to either the WDEP group or the usual care group. The effects of the WDEP on readmission within 90 days after discharge were analyzed using Cox proportional hazards models. Factors influencing treatment cost were identified using generalized linear model with log-link function and gamma distribution. Main outcome measure Hospital readmission within 90 days and treatment costs associated with hospital readmission. Results Among 692 eligible patients, 203 in each group were matched using propensity scores and there were no statistically significant differences in the patient baseline characteristics between two groups. The risk of all-cause readmission within 90 days was significantly lower in the WDEP group compared to the usual care group (relative risk = 0.46, 95% CI 0.28–0.76). The treatment costs associated with hospital readmission in the WDEP group were 19% lower than those in the usual care group after adjusting for the study variables. Conclusion A formal, individualized WDEP provided by pharmacists resulted in significant reduction of readmission and treatment costs. The economic burden of treatment costs associated with warfarin can be controlled if well-organized warfarin education is provided to patients who received warfarin therapy.

https://ift.tt/2GpHv26

Precision medicine becomes reality—tumor type-agnostic therapy

Abstract

Precision medicine just witnessed two breakthroughs in oncology in 2017. Pembrolizumab (Keytruda), Merck's anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), received accelerated approval in May 2017 by the US Food and Drug Administration for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having microsatellite instability-high (MSI-H) or deficient DNA mismatch repair (dMMR). Shortly after, nivolumab (Opdivo), Bristol-Myers Squibb's anti-PD-1 mAb, gained an accelerated approval in August 2017 for adult and pediatric patients with MSI-H or dMMR metastatic colorectal cancer that has progressed after standard chemotherapy. These regulatory approvals marked an important milestone that a cancer treatment may be approved based on a common biomarker rather than the anatomic location in the body where the tumor originated, and therefore established a precedent for tumor type-agnostic therapy. In the 2017 American Society for Clinical Oncology annual meeting, larotrectinib (LOXO-101), Loxooncology's oral, potent, and selective inhibitor of tropomyosin receptor kinases (TRK), demonstrated unprecedented efficacy on unresectable or metastatic solid tumors with neurotrophic tropomyosin receptor kinase (NTRK)-fusion proteins in adult and pediatric patients. Both the anti-PD-1 mAbs and the TRK-targeting therapies share some basic features: (a) biomarker-based, well-defined rare patient population; (b) exceptionally high clinical efficacy, e.g., near 40% overall response rate (ORR) for pembrolizumab across 15 tumor types with MSI-H/dMMR and 75% ORR for larotrectinib across more than 12 tumor types with NTRK-fusion proteins; (c) durable responses lasting at least 6 months with complete responses observed; and (d) parallel development in adult and pediatric populations. With increasing accessibility to genetic analysis tools such as next-generation sequencing, tumor type-agnostic therapy has become a reality, both during clinical development and in clinical practice. Adjustments in our approaches to developing new anti-cancer drugs and to adopting these new cancer treatments in clinical practice need to occur in order to prepare ourselves for the new era of precision medicine.

https://ift.tt/2GHadyD

Selection of candidates for surgery as local therapy among early-stage small cell lung cancer patients: a population-based analysis

Abstract

Background

Surgery and radiotherapy are considered local therapies for small cell lung cancer (SCLC). The present study aimed to select candidates for surgery as local therapy among patients with stage I or II SCLC, based on the eighth edition of the TNM classification for lung cancer.

Methods

Patients diagnosed with SCLC between 2004 and 2013 were selected from the Surveillance, Epidemiology, And End Results database. The TNM stage of SCLC in these patients was re-classified according to the eighth edition of the TNM classification for lung cancer. Patients with stage I or II SCLC were included in the present study. Overall survival (OS) and lung cancer-specific survival (LCSS) were separately compared in the different TNM stages between patients who received surgery and radiotherapy as local therapy. Multivariate analysis was applied to evaluate multiple factors associated with survival.

Results

Among the 2129 patients included in the present study, 387 (18.2%) received surgery, 1032 (48.5%) underwent radiotherapy as local therapy, 154 (7.2%) underwent surgery and radiotherapy, and 556 (26.1%) did not undergo either surgery or radiotherapy. Among patients with T1-2N0 (tumor size ≤ 50 mm without positive lymph nodes) disease, patients who underwent surgery had higher 5-year OS and LCSS rates than patients who received radiotherapy (T1N0: 46.0% vs. 23.8%, P < 0.001, and 58.4% vs. 36.4%, P < 0.001, respectively; T2N0: 42.6% vs. 24.7%, P = 0.004, and 48.8% vs. 31.3%, P = 0.011, respectively). Multivariate analysis results revealed that surgery was associated with low risk of death. However, among T3N0 or T1-2N1 (stage IIB) SCLC patients, patients who underwent surgery did not have higher 5-year OS and LCSS rates than patients who received radiotherapy (T3N0: 16.2% vs. 26.5%, P = 0.085, and 28.7% vs. 30.9%, P = 0.372, respectively; T1-2N1: 20.3% vs. 29.0%, P = 0.146, and 25.6% vs. 35.5%, P = 0.064, respectively).

Conclusions

Based on the assumption that the overwhelming majority of stage I or II SCLC patients who underwent surgery or radiotherapy also received certain types of systemic therapy, only patients with T1-2N0 SCLC may benefit from surgery as local therapy. Patients with T3N0 or T1-2N1 SCLC may consider radiotherapy as local therapy.

https://ift.tt/2GnwZZ4

Aiding the Detection of QRS Complex in ECG Signals by Detecting S Peaks Independently

Abstract

In this paper, a novel algorithm for the accurate detection of QRS complex by combining the independent detection of R and S peaks, using fusion algorithm is proposed. R peak detection has been extensively studied and is being used to detect the QRS complex. Whereas, S peaks, which is also part of QRS complex can be independently detected to aid the detection of QRS complex. In this paper, we suggest a method to first estimate S peak from raw ECG signal and then use them to aid the detection of QRS complex. The amplitude of S peak in ECG signal is relatively weak than corresponding R peak, which is traditionally used for the detection of QRS complex, therefore, an appropriate digital filter is designed to enhance the S peaks. These enhanced S peaks are then detected by adaptive thresholding. The algorithm is validated on all the signals of MIT-BIH arrhythmia database and noise stress database taken from physionet.org. The algorithm performs reasonably well even for the signals highly corrupted by noise. The algorithm performance is confirmed by sensitivity and positive predictivity of 99.99% and the detection accuracy of 99.98% for QRS complex detection. The number of false positives and false negatives resulted while analysis has been drastically reduced to 80 and 42 against the 98 and 84 the best results reported so far.

https://ift.tt/2pTjcmM

Nickel doping effect on properties of sprayed In 2 S 3 films

Abstract

Nickel doped In₂S₃ films have been prepared by the chemical spray pyrolysis technique at 350 °C on glass substrates. The Ni doping level was changed by varying Ni:In molar ratio from 0 to 4% in solution. The structural studies reveal that the Ni-doped In₂S₃ films are polycrystalline and exhibit a cubic structure. As the Ni:In molar ratio increases, the crystallite size decreases from 27.5 to 23 nm and RMS roughness values increase from 12 to 18 nm, respectively. The presence of Ni in the deposited films was confirmed by energy dispersive spectroscopy. Raman studies show different peaks related to In₂S₃ phase and do not reveal any secondary phases of In–Ni and Ni–S. The transmission coefficient is about 70–55% in the visible region and 85–75% in near-infrared region. The band gap energy increases from 2.66 to 2.82 eV for direct transitions with the increase of Ni:In ratio from 0 to 4%. The refractive index values of In₂S₃:Ni thin films decrease from 2.46 to 2.40 and the extinction coefficient values are in the range 0.01–0.20.

https://ift.tt/2pRuqIC

Analysis of Electroencephalography Event-Related Desynchronisation and Synchronisation Induced by Lower-Limb Stepping Motor Imagery

Abstract

Bilateral upper-limb motor imagery has been demonstrated to be a useful mental task in electroencephalography (EEG)-based brain–computer interfaces (BCIs). By contrast, few studies have examined bilateral lower-limb motor imagery, and all of them have focused on imaginary foot movements. The left–right classification accuracy reported in these studies based on the EEG mu rhythm (8–13 Hz) and beta band (13–30 Hz) remains unsatisfactory. The present study investigated the possibility of using lower-limb stepping motor imagery as the mental task and analysed the EEG difference between imaginary left-leg stepping (L-stepping) and right-leg stepping (R-stepping) movements. An experimental paradigm was designed to collect 5-s motor imagery EEG signals at nine recording sites around the vertex of the brain. Results from eight able-bodied participants indicated that the commonly used mu event-related desynchronisation (ERD) feature exhibited no significant difference between the two imaginary movements for all recording sites and all time intervals within the 5-s motor imagery period. Regarding the other commonly used feature, beta event-related synchronisation, no significant difference between the two imagery tasks was observed for most of the recording sites and time intervals. Instead, theta band (4–8 Hz) ERD significantly differed between the L- and R-stepping imagery tasks at five sites (FC4, C3, CP3, Cz, CPz) within the first 2 s after motor imagery cue onset. The findings from the present study may be a basis for further development of BCI systems for decoding left and right stepping during mental exercise where the two motions are alternately imagined.

https://ift.tt/2E7WADg

Genipin-Cross-Linked Chitosan Nerve Conduits Containing TNF-α Inhibitors for Peripheral Nerve Repair

Abstract

Tissue engineered nerve grafts (TENGs) are considered a promising alternative to autologous nerve grafting, which is considered the "gold standard" clinical strategy for peripheral nerve repair. Here, we immobilized tumor necrosis factor-α (TNF-α) inhibitors onto a nerve conduit, which was introduced into a chitosan (CS) matrix scaffold utilizing genipin (GP) as the crosslinking agent, to fabricate CS-GP-TNF-α inhibitor nerve conduits. The in vitro release kinetics of TNF-α inhibitors from the CS-GP-TNF-α inhibitor nerve conduits were investigated using high-performance liquid chromatography. The in vivo continuous release profile of the TNF-α inhibitors released from the CS-GP-TNF-α inhibitor nerve conduits was measured using an enzyme-linked immunosorbent assay over 14 days. We found that the amount of TNF-α inhibitors released decreased with time after the bridging of the sciatic nerve defects in rats. Moreover, 4 and 12 weeks after surgery, histological analyses and functional evaluations were carried out to assess the influence of the TENG on regeneration. Immunochemistry performed 4 weeks after grafting to assess early regeneration outcomes revealed that the TENG strikingly promoted axonal outgrowth. Twelve weeks after grafting, the TENG accelerated myelin sheath formation, as well as functional restoration. In general, the regenerative outcomes following TENG more closely paralleled findings observed with autologous grafting than the use of the CS matrix scaffold. Collectively, our data indicate that the CS-GP-TNF-α inhibitor nerve conduits comprised an elaborate system for sustained release of TNF-α inhibitors in vitro, while studies in vivo demonstrated that the TENG could accelerate regenerating axonal outgrowth and functional restoration. The introduction of CS-GP-TNF-α-inhibitor nerve conduits into a scaffold may contribute to an efficient and adaptive immune microenvironment that can be used to facilitate peripheral nerve repair.

https://ift.tt/2E6ZOY1

Discrimination of Isomers of Released N- and O- Glycans Using Diagnostic Product Ions in Negative Ion PGC-LC-ESI-MS/MS

Abstract

Profiling cellular protein glycosylation is challenging due to the presence of highly similar glycan structures that play diverse roles in cellular physiology. As the anomericity and the exact linkage type of a single glycosidic bond can influence glycan function, there is a demand for improved and automated methods to confirm detailed structural features and to discriminate between structurally similar isomers, overcoming a significant bottleneck in the analysis of data generated by glycomics experiments. We used porous graphitized carbon-LC-ESI-MS/MS to separate and detect released N- and O-glycan isomers from mammalian model glycoproteins using negative mode resonance activation CID-MS/MS. By interrogating similar fragment spectra from closely related glycan isomers that differ only in arm position and sialyl linkage, product fragment ions for discrimination between these features were discovered. Using the Skyline software, at least two diagnostic fragment ions of high specificity were validated for automated discrimination of sialylation and arm position in N-glycan structures, and sialylation in O-glycan structures, complementing existing structural diagnostic ions. These diagnostic ions were shown to be useful for isomer discrimination using both linear and 3D ion trap mass spectrometers when analyzing complex glycan mixtures from cell lysates. Skyline was found to serve as a useful tool for automated assessment of glycan isomer discrimination. This platform-independent workflow can potentially be extended to automate the characterization and quantitation of other challenging glycan isomers.

Graphical Abstract

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https://ift.tt/2Gmbiwq

Fast 5DOF needle tracking in iOCT

Abstract

Purpose

Intraoperative optical coherence tomography (iOCT) is an increasingly available imaging technique for ophthalmic microsurgery that provides high-resolution cross-sectional information of the surgical scene. We propose to build on its desirable qualities and present a method for tracking the orientation and location of a surgical needle. Thereby, we enable the direct analysis of instrument–tissue interaction directly in OCT space without complex multimodal calibration that would be required with traditional instrument tracking methods.

Method

The intersection of the needle with the iOCT scan is detected by a peculiar multistep ellipse fitting that takes advantage of the directionality of the modality. The geometric modeling allows us to use the ellipse parameters and provide them into a latency-aware estimator to infer the 5DOF pose during needle movement.

Results

Experiments on phantom data and ex vivo porcine eyes indicate that the algorithm retains angular precision especially during lateral needle movement and provides a more robust and consistent estimation than baseline methods.

Conclusion

Using solely cross-sectional iOCT information, we are able to successfully and robustly estimate a 5DOF pose of the instrument in less than 5.4 ms on a CPU.

https://ift.tt/2IhUPG2

IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells

Abstract

IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11Rα was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11Rα strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11Rα can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.

https://ift.tt/2CSh6bc

Detection of architectural distortion from the ridges in a digitized mammogram

Abstract

Architectural distortion (AD) has been described as a focal retraction of the breast tissue. Blood vessels, milk ducts and spicules in the breast tissue appear as ridges in the mammogram. We hypothesize that radiating ridges are an indicator of an AD site. Using a window-based approach, features derived from the ridges have been utilized in a radial basis function support vector machine to classify regions as containing or not containing AD. The classification is performed on the Mammographic Image Analysis Society (MIAS) database and on the Digital Database For Screening Mammography (DDSM). The proposed approach reports peak performance of a sensitivity of 90% (93%) at 26 (17) false positives per mammogram in the MIAS (DDSM) database.

https://ift.tt/2GJO0QR

Study of the physical discharge properties of a Ar/O 2 DC plasma jet

Abstract

In this paper, the physical properties of plasma discharge in a manufactured DC plasma jet operating with the Ar/O₂ gaseous mixture are studied. Moreover, the optical emission spectroscopy technique is used to perform the experimental measurements. The obtained emission spectra are analyzed and, the plasma density, rotational, vibrational and electronic temperature are calculated. The NO emission lines from \( {\text{NO }}\upgamma \left( ^{2} ^{ + } \to {\text{X}}^{2} _{\text{r}} } \right) \) electronic transition are observed. It is seen that, at the higher argon contributions in Ar/O₂ gaseous mixture, the emission intensities from argon ions will increase. Moreover, while the vibrational and excitation temperatures are increased at the higher input DC currents, they will decrease at the higher Ar percentages in the Ar/O₂ gaseous mixture. Furthermore, at the higher DC currents and Ar contributions, both the plasma electron density and dissociation fraction of oxygen atoms are increased.

https://ift.tt/2J7GhKr

Wound measurement by RGB-D camera

Abstract

The robot and computer vision community has seen a lot of novelties developed in the past few years as a result of the appearance of cheap RGB-D sensors spearheaded by the Kinect sensor. In this paper, the feasibility of using an RGB-D camera in detecting, segmenting, reconstructing and measuring chronic wounds in 3D is explored. The wound is detected by implementing nearest-neighbor approach on color histograms generated from the image. The proposed wound segmentation procedure extracts the wound contour using visual and geometrical information of the surface. A procedure comparable to KinectFusion is used for the 3D reconstruction of the wound. In order to achieve real-time performance, the whole system is realized in CUDA. The resulting system provides an accurate colored 3D model of the segmented wound and enables the user to determine the volume, area and perimeter of the wound, thereby aiding in the selection of a suitable therapy. The developed system is experimentally evaluated using the Saymour II wound care model by VATA Inc.

https://ift.tt/2uDbDFU

Use of Proton Pump Inhibitors and the Risk of Acute Kidney Injury Among Patients with Rheumatoid Arthritis: Cohort Study

Abstract

Introduction

Recent observational studies have indicated that use of proton pump inhibitors may be associated with adverse renal outcomes. The objective of this study was to investigate whether the use of proton pump inhibitors increases the risk of acute kidney injury among patients with rheumatoid arthritis.

Methods

We conducted the study as a historical prospective cohort study, including patients with rheumatoid arthritis, 30–84 years of age, during 2004–2015. Among these, we identified and matched episodes of use and non-use of proton pump inhibitors (control episodes) 1:4 on the propensity score, including 24,579 episodes of use of proton pump inhibitors and 98,230 control episodes. The primary outcome was a first diagnosis of acute kidney injury and the secondary outcome was any serious renal event (acute kidney injury or chronic kidney disease). The primary time point for analysis was 120 days after study entry.

Results

The incidence rate of acute kidney injury was 2.2 per 1000 person-years during episodes of use of proton pump inhibitors and 0.9 during control episodes. Use of proton pump inhibitors was associated with a significantly increased risk of acute kidney injury (hazard ratio 2.30, 95% confidence interval 1.26–4.20). The absolute risk difference was 40 (95% confidence interval 8–99) events of acute kidney injury per 100,000 episodes of use of proton pump inhibitors. Use of proton pump inhibitors was also associated with a significantly increased risk of the secondary outcome of any serious renal event (hazard ratio 2.61, 95% confidence interval 1.80–3.80).

Conclusions

This cohort study among patients with rheumatoid arthritis found a significantly increased risk of acute kidney injury associated with the use of proton pump inhibitors. These findings may help inform clinical decision making when considering the risks and benefits of proton pump inhibitor treatment in rheumatoid arthritis.

https://ift.tt/2pT1Cid

Post-deployment Mental Health Screening: A Systematic Review of Current Evidence and Future Directions

Abstract

Population-based post-deployment screening programs within the Departments of Defense and Veterans Affairs have been implemented to assess for mental health conditions and traumatic brain injury. The purpose of this paper is to systematically review the literature on post-deployment screening within this context and evaluate evidence compared to commonly accepted screening implementation criteria. Findings reflected highly variable psychometric properties of the various screens, variable treatment referral rates following screening, low to moderate treatment initiation rates following screening, and no information on treatment completion or long-term outcomes following screening. In sum, the evidence supporting population based post-deployment screening is inconclusive. Implications are discussed.

https://ift.tt/2pQIYYT

Impact of Long-Term Perfluorooctanoic Acid (PFOA) Exposure on Activated Sludge Process

Abstract

Poly- and perfluorinated alkyl substances (PFASs) are groups of persistent toxic substances that have been commonly detected in wastewater treatment plants (WWTPs). In some cases, the activated sludge (AS) in WWTPs will encounter special wastewaters containing PFASs up to tens of milligram per liter (mg L⁻¹). However, under this condition, the potential impacts of PFASs on AS process remain unclear. In the present research, a lab-scale sequencing batch reactor was continuously exposed to perfluorooctanoic acid (PFOA), used as a representation for PFASs, at 20 mg L⁻¹ to mimic the extreme condition. The objective is to explore the impact of PFOA on AS process in terms of its wastewater treatment performance and evolution of microbial communities. The results indicate that PFOA restrained the microbial growth and affected the dissolved organic carbon removal. These negative impacts could be recovered after long-term adaptation. Besides, 20 mg L⁻¹ PFOA shows limited inhibition on nitrification and denitrification, suggesting a safe exposure level of PFOA for nitrogen removal. For microbial evolution, PFOA induced changes of communities during long-term exposure. The high abundance of Bacteroidetes, Proteobacteria, and Acidobacteria maintained over time reveals their tolerance towards PFOA. The occurrences of PFOA-resistant species are also observed. The present research provides new insight into the possible impacts of typical PFAS at high concentrations on AS process.

https://ift.tt/2pSW733

DNA methylation of genes regulating appetite and prediction of weight loss after bariatric surgery in obese individuals

Abstract

Purpose

Epigenetic traits are influenced by clinical variables; interaction between DNA methylation (DNAmeth) and bariatric surgery-induced weight loss has been scarcely explored. We investigated whether DNAmeth of genes encoding for molecules/hormones regulating appetite, food intake or obesity could predict successful weight outcome following Roux-en-Y gastric bypass (RYGB).

Methods

Forty-five obese individuals with no known comorbidities were stratified accordingly to weight decrease one-year after RYGB (excess weight loss, EWL ≥ 50%: good responders, GR; EWL < 50%: worse responders, WR). DNAmeth of leptin (LEP), ghrelin (GHRL), ghrelin receptor (GHSR) and insulin-growth factor-2 (IGF2) was assessed before intervention. Single nucleotide polymorphisms of genes affecting DNAmeth, DNMT3A and DNMT3B, were also determined.

Results

At baseline, type 2 diabetes was diagnosed by OGTT in 13 patients. Post-operatively, GR (n = 23) and WR (n = 22) achieved an EWL of 67.7 ± 9.6 vs 38.2 ± 9.0%, respectively. Baseline DNAmeth did not differ between GR and WR for any tested genes, even when the analysis was restricted to subjects with no diabetes. A relationship between GHRL and LEP methylation profiles emerged (r = 0.47, p = 0.001). Searching for correlation between DNAmeth of the studied genes with demographic characteristics and baseline biochemical parameters of the studied population, we observed a correlation between IGF2 methylation and folate (r = 0.44, p = 0.003). Rs11683424 for DNMT3A and rs2424913 for DNMT3B did not correlate with DNAmeth of the studied genes.

Conclusions

In severely obese subjects, the degree of DNAmeth of some genes affecting obesity and related conditions does not work as predictor of successful response to RYGB.

https://ift.tt/2pRUfY9

Hierarchical prediction-based motion vector refinement for video frame-rate up-conversion

Abstract

Motion-compensated frame-rate up-conversion (MC-FRUC) often exploits either bilateral motion estimation (ME) or unidirectional ME with a fixed block size, which constrains the perceptual quality of up-converted video. In this paper, an advanced MC-FRUC approach is proposed by exploiting hierarchical prediction-based motion vector refinement. To reduce block mismatching in texture regions and color areas, an adaptive multi-layered block matching criterion is designed to extract color and edge information, which is integrated with motion information as constraint term. A hierarchical prediction-based motion vector refinement approach is proposed to obtain more accurate and dense motion vector fields (MVFs). To eliminate the outliers of MVFs, a robust dual-weighted motion vector smoothing scheme is adopted by using both spatial correlation and reliability of neighboring blocks. Experimental results show that the proposed approach has low computational complexity and outperforms state-of-the-art works in both objective and subjective qualities of interpolated frames.

https://ift.tt/2GjCo7q

Chinese Children’s Knowledge of Topicalization: Experimental Evidence from a Comprehension Study

Abstract

There is a debate as to whether topic structures in Chinese involve A'-movement or result from base-generation of the topic in the left periphery. If Chinese topicalization was derived by movement, under the assumptions of Friedmann et al.'s Relativized Minimality (Lingua 119:67–88, 2009), we would expect children's comprehension of object topicalization (with OSV order) to be worse than their comprehension of subject topicalization (with SVO order). This study examined 146 Mandarin-speaking children from age three to age six by means of a picture-sentence matching task with an appropriate context. The results showed a subject/object asymmetry when the topic marker is overt, and no asymmetry when the topic marker is covert. This suggests that the presence or absence of topic markers play an important role in children's comprehension of topicalization. We propose that both structures involve movement in the adult grammar, but not in the child grammar, at least initially. Sentences without overt topic markers are base-generated on a par with gapless sentences with a topic, and the base-generation analysis is abandoned as soon as children learn the syntax and semantics of topic markers, which function as attractors of topics.

https://ift.tt/2pShWiY

The Dysphagia in Stroke Protocol Reduces Aspiration Pneumonia in Patients with Dysphagia Following Acute Stroke: a Clinical Audit

Abstract

Cough reflex testing has been evaluated as a component of the clinical swallowing assessment as a means of identifying patients at risk of aspiration during swallowing. A previous study by our research group found good sensitivity and specificity of the cough reflex test for identifying patients at risk of aspiration post-stroke, yet its use did not decrease pneumonia rates, contrary to previous reports. The aim of this study was to expand on our earlier work by implementing a clinical management protocol incorporating cough reflex testing within the same healthcare setting and compare patient outcomes to those from the original study and to evaluate clinical outcomes in patients with acute stroke who were managed using the Dysphagia in Stroke Protocol (DiSP). Secondarily, to compare those outcomes to historical data prior to implementation of the DiSP. This clinical audit measured outcomes from 284 patients with acute stroke managed per the DiSP, which guides use of videofluoroscopic swallowing study and patient management based on clinical exam with cough reflex testing. Data from our previous trial were included for comparison of pre- and post-DiSP patient outcomes. Data collection took place between November 2012 and April 2016 at four urban hospitals within New Zealand. Following implementation of the DiSP, the rate of aspiration pneumonia (10%) was substantially lower than the pre-DiSP rate (28%), with no pneumonia readmissions within 3 months. Pneumonia-related mortality was unchanged. By 3 months, 81% of the patients were on a normal diet and 67% had returned home, compared to pre-DiSP outcomes of 55% and 55% respectively. Previous work has suggested that simply implementing cough reflex testing in dysphagia management may not be sufficient to improve patient outcomes. The present study adds to this picture by suggesting that the true variable of influence may be the way in which the results of the test are applied to patient care. There is a strong case to support the use of a structured protocol if cough reflex testing is to be implemented in clinical practice.

https://ift.tt/2IfKaM5

Do clinical criteria reflect pathologic complete response in rectal cancer following neoadjuvant therapy?

Abstract

Background

Clinical complete response (cCR) in rectal cancer is being evaluated as a tool to identify patients who would not require surgery in the curative management of rectal cancer. Our study reviews mucosal changes after neoadjuvant therapy for rectal cancer in patients treated at our center.

Methods

Pathology reports were retrieved for patients treated with neoadjuvant chemoradiation therapy (CRT) or high-dose rate brachytherapy (HDRBT). The macroscopic appearance of the specimen was compared with pathologic staging.

Results

This study included 282 patients: 88 patients underwent neoadjuvant CRT and 194 patients underwent HDRBT; all patients underwent total mesorectal excision (TME). There were 160 male and 122 female patients with a median age of 65 years (range 29–87). The median time between neoadjuvant therapy and surgery was 50 and 58 days. Sixty patients (21.2%) were staged as ypT0N0, 21.2% had a pathologic complete response (pCR), and only 3.2% had a cCR. Of the 67 patients with initial involvement of the circumferential radial margin (CRM), 44 converted to pathologic CRM−. Two hundred seventy-three patients (96.8%) had mucosal abnormalities. Of the 222 patients with residual tumor, 70 patients had no macroscopic tumor visualized but an ulcer in its place.

Conclusion

Most patients undergoing neoadjuvant therapy for rectal cancer have residual mucosal abnormalities which preclude to a cCR as per published criteria from Brazil. Further studies are required to optimize clinical evaluation and MRI imaging in selected patients.

https://ift.tt/2GkX4MD

Wall thickness control in biotubes prepared using type-C mold

Abstract

A type-C mold based on in-body tissue architecture was previously developed for preparing small-diameter biotube vascular grafts with a 2-mm diameter and approximately 1-mm wall thickness. In this study, the type-C mold was modified for preparing large-diameter biotubes with controlled wall thicknesses. Four types of molds were assembled by inserting silicone center rods (outer diameters 11, 13, 15, 17 mm) into stainless steel cages (inner diameter 19 mm) and surgically embedded in the abdominal subcutaneous pouches of Holstein cows. After 8–12 weeks, connective tissues occupied the rod–cage gap in the molds to form biotubes. The wall thickness of the biotubes obtained after removing the molds was approximately 1–3 mm, which corresponded to approximately 80% of each gap distance. The breaking strength almost linearly increased with the wall thickness of the biotubes. The strength of the biotubes with wall thickness over 1.5 mm was higher than that of beagle blood vessels. The thickest biotubes were as strong as bovine pericardium and can be used as an alternative trachea graft because of their adequate lumen-holding force.

https://ift.tt/2uBBzl4

Comparison of abdominal radiographs and sonography in prognostic prediction of infants with necrotizing enterocolitis

Abstract

Purpose

The purpose of this study was to investigate the comparison of AR and AUS in predicting prognosis in infants with necrotizing enterocolitis.

Methods

All patients were diagnosed as NEC at the department of general surgery and neonatal surgery, Qilu children's hospital between 1st, Jun, 2010 and 30th, Dec, 2016. The logistic regression analysis and the area under ROC curve (AUC)s were also used to compare the prognostic values of radiograph and sonograph for NEC.

Results

Throughout the study period, 86 preterm neonates were hospitalized with diagnosis of definite NEC. Among these patients, 39 infants (45.3%) required surgical treatment. After adjusting for competing sonographic factors, we identified that thick bowel wall (more than 2.5 mm) (p = 0.001, HR: 1.849), intramural gas (pneumatosis intestinalis) (p = 0.017, HR: 1.265), portal venous gas (p = 0.002, HR: 1.824), and reduced peristalsis (p = 0.021, HR: 1.544) were independent prognostic factors associated with NEC. After adjusting for competing radiographic factors, we identified that free peritoneal gas (p = 0.007, HR: 1.472), portal venous gas (p = 0.012, HR: 1.649), and dilatation and elongation (p = 0.025, HR: 1.327). Moreover, we found that the AUROC for AR logistic model was 0.745 (95% CI 0.629–0.812), which was significant lower than the AUS logistic model (AUROC: 0.857, 95% CI 0.802–0.946) for predicting prognosis of NEC.

Conclusions

In conclusion, we found that several radiographic and sonographic parameters were associated with the prognosis of patients with NEC. The AUS model based on the logistic regression analysis was significant superior to the AR model in the prognostic prediction of NEC.

https://ift.tt/2GHtPCY

Convolutional Neural Networks for Electrocardiogram Classification

Abstract

In this paper, we propose a transfer learning approach for Arrhythmia Detection and Classification in Cross ECG Databases. This approach relies on a deep convolutional neural network (CNN) pretrained on an auxiliary domain (called ImageNet) with very large labelled images coupled with an additional network composed of fully connected layers. As the pretrained CNN accepts only RGB images as the input, we apply continuous wavelet transform (CWT) to the ECG signals under analysis to generate an over-complete time–frequency representation. Then, we feed the resulting image-like representations as inputs into the pretrained CNN to generate the CNN features. Next, we train the additional fully connected network on the ECG labeled data represented by the CNN features in a supervised way by minimizing cross-entropy error with dropout regularization. The experiments reported in the MIT-BIH arrhythmia, the INCART and the SVDB databases show that the proposed method can achieve better results for the detection of ventricular ectopic beats (VEB) and supraventricular ectopic beats (SVEB) compared to state-of-the-art methods.

https://ift.tt/2Gmj05S

Population pharmacokinetics of vancomycin and AUC-guided dosing in Chinese neonates and young infants

Abstract

Objectives

To develop a population pharmacokinetic (PK) model for vancomycin in Chinese neonates and infants less than 2 months of age (young infants) with a wide gestational age range, in order to determine the appropriate dosing regimen for this population.

Methods

We performed a retrospective chart review of patients from the neonatal intensive care unit (NICU) at Children's Hospital of Fudan University to identify neonates and young infants treated with vancomycin from May 2014 to May 2017. Vancomycin concentrations and covariates were utilized to develop a one-compartment model with first-order elimination. The predictive performance of the final model was assessed by both internal and external evaluation, and the relationship between trough concentration and AUC_0–24 was investigated. Monte Carlo simulations were performed to design an initial dosing schedule targeting an AUC_0–24 ≥ 400.

Results

The analysis included a total of 330 concentration–time data points from 213 neonates and young infants with gestational age (GA) and body weight of 25–42 weeks and 0.88–5.1 kg, respectively. Body weight, postmenstrual age (PMA) and serum creatinine level were found to be important factors explaining the between-subject variability in vancomycin PK parameters for this population. Both internal and external evaluation supported the prediction of the final vancomycin PK model. The typical population parameter estimates of clearance and distribution volume for an infant weighing 2.73 kg with a PMA of 39.8 weeks and serum creatinine of 0.28 mg/dL were 0.103 L/h/kg and 0.58 L/kg, respectively. Although vancomycin serum trough concentrations were predictive of the AUC, considerable variability was observed in the achievement of an AUC_0–24/MIC of ≥400. For MIC values of ≤0.5 mg/L, AUC_0–24/MIC ≥400 was achieved for 95% of the newborn infants with vancomycin troughs of 5–10 mg/L. When the MIC increased to 1 mg/L, only 15% of the patients with troughs of 5–10 mg/L achieved AUC_0–24/MIC ≥400. For MIC values of 2 mg/L, no infants achieved the target. Simulations predicted that a dose of at least 14 and 15 mg/kg every 12 h was required to attain the target AUC_0–24 ≥ 400 in 90% of infants with a PMA of 30–32 and 32–34 weeks, respectively. This target was also achieved in 93% of simulated infants in the oldest PMA groups (36–38 and 38–40 weeks, respectively) when the dosing interval was extended to 8 h. For infants with a PMA ≥44 weeks, a dose increase to 18 mg/kg every 8 h was needed. The trough concentrations of 5–15 mg/L were highly predictive of an AUC_0–24 of ≥400 when treating invasive MRSA infections with an MIC of ≤1 mg/L.

Conclusions

The PK parameters for vancomycin in Chinese infants younger than 2 months of age were estimated using the model developed herein. This model has been used to predict individualized dosing regimens in this vulnerable population in our hospital. A large external evaluation of our model will be conducted in future studies.

https://ift.tt/2uyiNLw

Analyzing large-scale human mobility data: a survey of machine learning methods and applications

Abstract

Human mobility patterns reflect many aspects of life, from the global spread of infectious diseases to urban planning and daily commute patterns. In recent years, the prevalence of positioning methods and technologies, such as the global positioning system, cellular radio tower geo-positioning, and WiFi positioning systems, has driven efforts to collect human mobility data and to mine patterns of interest within these data in order to promote the development of location-based services and applications. The efforts to mine significant patterns within large-scale, high-dimensional mobility data have solicited use of advanced analysis techniques, usually based on machine learning methods, and therefore, in this paper, we survey and assess different approaches and models that analyze and learn human mobility patterns using mainly machine learning methods. We categorize these approaches and models in a taxonomy based on their positioning characteristics, the scale of analysis, the properties of the modeling approach, and the class of applications they can serve. We find that these applications can be categorized into three classes: user modeling, place modeling, and trajectory modeling, each class with its characteristics. Finally, we analyze the short-term trends and future challenges of human mobility analysis.

https://ift.tt/2GWDDGW

Correction to: Global and Japanese regional variations in radiologist potential workload for computed tomography and magnetic resonance imaging examinations

Abstract

In Results of Abstract, the first sentence should read as: The radiologist potential workload in Japan was 2.78–4.17 times higher than those in other countries.

https://ift.tt/2E4j8EZ

Predictors of self-medication in Serbian adult population: cross-sectional study

Abstract

Background In spite of many benefits for individuals and community, self-medication has a number of potential risks. Objective To identify predictors of self-medication with over-the-counter and prescription (Rx) medicines without doctor's prescription. Setting Serbian population of 15 years of age and over. Method This was crosssectional, epidemiological study. Data have been drawn from Serbian National Health Survey 2013 database. Predictors of self-medication were determined among sociodemographic, health related and health services related factors, using multivariate logistic regression models. Main outcome measure Prevalence and predictors of selfmedication. Results The study included 14,623 participants. The prevalence of selfmedication was 27.1 and 24% after exclusion of vitamins, minerals and herbal preparations. Medicines for pain relief were the mostly used medicines without doctors' prescription in 18.4% of participants. A relatively high prevalence of self-medication with Rx medicines, (1) tranquilizers and sleeping pills, (2) antibiotics and (3) antihypertensives, was found, 4, 2.5 and 1.9%, respectively. Socio-demographic factors (middle age, female gender, higher level of education), health related factors (chronic disease, stress, physical pain), and health service related factors (nonrealized healthcare needs due to long waiting, dissatisfaction with publicly funded health services) have been found as significantly associated with self-medication. Conclusion Self-medication in Serbia is predicted by socio-demographic and health related factors, unmet needs for healthcare and dissatisfaction with publicly funded healthcare services. Improvements in healthcare system, particularly, shortening of long waiting for healthcare services and improvements in pharmaceutical services, particularly better control of Rx medicines dispensing, could contribute in improvement of responsible self-medication.

https://ift.tt/2Gjqmeg

Impact of the clinical pharmacist interventions on prevention of pharmacotherapy related problems in the paediatric intensive care unit

Abstract

Background Problems related to pharmacotherapy are common in patients admitted to the paediatric intensive care unit (PICU) and are associated with increased healthcare costs. Data on the impact of clinical pharmacist interventions to prevent pharmacotherapy-related problems and to minimize costs in the PICU are limited. Objectives To evaluate the number and type of clinical pharmacist interventions in the PICU and to determine cost savings associated with them. Setting a ten bed PICU of a tertiary-care university hospital in Brazil. Method This was a prospective, observational study conducted over 1-year. The Failure Mode and Effects Analysis (FMEA) tool was applied at the beginning of the study to assess drug-related risks in the PICU and to guide clinical pharmacist interventions. Main outcome measure Number and type of clinical pharmacist interventions and healthcare-related costs. Results One hundred sixty-two children were followed-up by the clinical pharmacist and 1586 prescriptions were evaluated; pharmacotherapy-related problems were identified in 12.4% of them. Sixteen of 75 failure modes identified by FMEA were potentially reduced by the clinical pharmacist interventions. There were 197 interventions with a cost saving of R$ 15,118.73 (US$ 4828.00). Clinical pharmacist interventions were related to drug interaction and therapeutic monitoring (34.5%), drug selection (22.3%), dosing and frequency (16.8%), prescription (13.2%) and administration (13.2%). Ninety-seven per cent of the clinical pharmacist interventions were accepted by the medical team. The interventions with larger cost savings were related to administration (39%). Conclusion The clinical pharmacist interventions minimized the risks of pharmacotherapy-related problems and contributed to the reduction of costs associated with medical prescription.

https://ift.tt/2E6OevU

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-β-cyclodextrin conjugate forming inclusion complexes with dexamethasone

Abstract

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-β-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

https://ift.tt/2J4giDI

Investigation on the in vitro cytocompatibility of Mg-Zn-Y-Nd-Zr alloys as degradable orthopaedic implant materials

Abstract

Mg-Zn-Y-Nd-Zr alloy has been developed as a new type of biodegradable orthopaedic implant material by the authors' research group with its excellent mechanical properties and controllable degradation rate. In this study, the cytocompatibility of Mg-Zn-Y-Nd-Zr alloy was systematically evaluated through in vitro cell culture method. MTT assay was applied to evaluate the cytotoxicity of Mg-Zn-Y-Nd-Zr alloy and no toxic effect was observed on L929 and MC3T3-E1 cells followed the protocol of ISO 10993 standard. Considering the potential ion accumulation in the bony environment, this study further investigated the cytotoxic effect of accumulated metallic ions during the alloy degradation by extending the extract preparation time. When the extract preparation time was prolonged to 1440 h, the accumulated metallic ions leaded to severe cell apoptosis, of which the combined ion concentration was determined as 39.5–65.8 µM of Mg²⁺, 3.5–5.9 µM of Zn²⁺, 0.44–0.74 µM of Y³⁺, 0.3–0.52 µM of Nd³⁺ and 0.11–0.18 µM of Zr⁴⁺ for L929, and 65.8–92.2 µM of Mg²⁺, 5.9–8.3 µM of Zn²⁺, 0.74–1.04 µM of Y³⁺, 0.52–0.73 µM of Nd³⁺ and 0.18–0.25 µM of Zr⁴⁺ for MC3T3-E1 cells. Besides the cell viability assessment, high expression of ALP activity and calcified nodules implied that metal elements in Mg-Zn-Y-Nd-Zr alloys can promote the osteogenic differentiation. Hence, excellent cytocompatibility has equipped Mg-Zn-Y-Nd-Zr alloy as a promising candidate for orthopaedic implant application, which can remarkably guide the magnesium-based alloy design and provide scientific evidence for clinical practice in future.

https://ift.tt/2pRJqFz

Comparison of early osseointegration between laser-treated/acid-etched and sandblasted/acid-etched titanium implant surfaces

Abstract

This study was designed to compare the early osseointegration of titanium surfaces prepared via laser-treated/acid-etched (LA) and sandblasted/acid-etched (SLA) in dogs. Titanium implants were divided into two groups: Surfaces of the experimental group were treated via LA, while in the control group, surfaces were treated via SLA. The physical and chemical properties of LA and SLA surfaces were tested and compared. Sixteen implants with LA or SLA surfaces were placed into the tibias of four beagle dogs, each treatment group received two implants per single tibia. The dogs were sacrificed two and four weeks after implant placement. Scanning electron microscopy showed that both the LA and SLAs surface exhibited rough structures with micro pores sized 1–3 μm. In the LA surface, regular melting points were observed. However, in the SLA surface, the structure was irregular and few oxide aluminum particles still remained. Only titanium and a small amount of titanium compounds were detected on LA surfaces, while Al was found of SLA surfaces. The LA surface roughness was above that of SLA surfaces (LA: Ra: 2.1 μm; SLA: Ra :1.53 μm; P < 0.01). Both groups exhibited good osseointegration and no significant differences were found in the BIC% at two or four weeks between both groups (P > 0.05). Both groups exhibited good osseointegration; however, the LA surface was cleaner and more uniform than the SLA surface, and no significant differences were found between both groups.

https://ift.tt/2J6Faea

Standardization of surgical procedures to reduce risk of anastomotic leakage, reoperation, and surgical site infection in colorectal cancer surgery: a retrospective cohort study of 1189 patients

Abstract

Purpose

Anastomotic leakage (AL) and surgical site infection (SSI) are prevalent complications of colorectal surgery. To lower this risk, we standardized our surgical procedures in 2012, with a preferential use of laparoscopic approach (LS) for both colon and rectal surgery, combined with triangulating anastomosis (TA) for colon surgery and defunctioning ileostomy (DI) for low anterior resection. Our aim was to evaluate the outcomes of our standardized procedures.

Methods

The incidence rate of AL (primary outcome) and of reoperation and SSI (secondary outcome) was compared before (early period, n = 648) and after (late period, n = 541) standardization, through a retrospective analysis.

Results

The incidence rate of AL (6.6 versus 1.8%; P = 0.001), reoperation (3.5 versus 0.7%; P = 0.0012), and SSI (7.7 versus 4.6%; P = 0.029) was lower in late than in the early period. For colon cancer, TA and LS reduced the risk of AL (2.1 versus 0.3%, P = 0.020, for TA, and 3.2 versus 0.4%, P = 0.0027, for LS) and reoperation (2.9 versus 0.3%, P = 0.003, for TA, and 2.5 versus 0.2%, P = 0.0040, for LS). For rectal cancer, the incidence of all adverse outcomes (AL, reoperation, and SSI) was lower in cases treated by LS. However, the incidence of AL was lower in the late than in early period (P = 0.002) and with LS (P = 0.002). On multivariate analysis, late period and LS were independent factors of a lower risk of adverse outcomes.

Conclusions

Our surgical standardization seems to be effective in lowering the risks of AL, reoperation, and SSI after colorectal cancer surgery.

https://ift.tt/2GpWqcB

LV function validation of computer-assisted interventional system for cardiac resyncronisation therapy

Abstract

Purpose

Cardiac resynchronisation therapy (CRT) is an established treatment for symptomatic patients with heart failure, a prolonged QRS duration, and impaired left ventricular (LV) function; however, non-response rates remain high. Recently proposed computer-assisted interventional platforms for CRT provide new routes to improving outcomes. Interventional systems must process information in an accurate, fast and highly automated way that is easy for the interventional cardiologists to use. In this paper, an interventional CRT platform is validated against two offline diagnostic tools to demonstrate that accurate information processing is possible in the time critical interventional setting.

Methods

The study consisted of 3 healthy volunteers and 16 patients with heart failure and conventional criteria for CRT. Data analysis included the calculation of end-diastolic volume, end-systolic volume, stroke volume and ejection fraction; computation of global volume over the cardiac cycle as well as time to maximal contraction expressed as a percentage of the total cardiac cycle.

Results

The results showed excellent correlation ( \(R^{2}\) values of \(>\,0.99\) and Pearson correlation coefficient of \(>\,0.98\) ) with comparable offline diagnostic tools.

Conclusion

Results confirm that our interventional system has good accuracy in everyday clinical practice and can be of clinical utility in identification of CRT responders and LV function assessment.

https://ift.tt/2GmhgJD

Assembly of bioconjugated rod-nanotags and multilayer plasmonic nanorod-array for ultrasensitive SERS detection of S. aureus bacteria

Abstract

A highly-efficient bioconjugation protocol of bimetallic rod-nanotags interacted with bacterial anti-S. aureus-IgG has been firstly demonstrated. Controllable fabrication of multilayer plasmonic nanorod-array (MPNRA) can be successfully obtained by facet functionalization of nanorods stacked on an activated Si/SiO₂ chip. Vancomycin coating of MPNRA is favorable to immobilize S. aureus bacteria via multiple hydrogen bonding interactions, i.e., peptidoglycan of the bacterial cell and carbonyl/amine groups of the vancomycin. Moreover, the bimetallic rod-nanotags can be assembled around MPNRA via a bacterial biointerface. Ultrasensitive SERS detection of S. aureus bacteria with limit-of-detection (LOD) can be achieved up to 17.8 cfu/mL via combination of rod-nanotag and multilayer plasmonic nanorod-array perpendicular a chip (MPNRA-perpendicular substrate), which could be ascribed to dual plasmonic enhancement from bioconjugated rod-nanotags aggregates and large-scaled plasmonic nanorod-array.

https://ift.tt/2GkReLf

Survival is influenced by approaches to local treatment of Ewing sarcoma within an international randomised controlled trial: analysis of EICESS-92

Abstract

Background

Two national clinical trial groups, United Kingdom Children's Cancer and Leukaemia Group (CCLG) and the German Paediatric Oncology and Haematology Group (GPOH) together undertook a randomised trial, EICESS-92, which addressed chemotherapy options for Ewing's sarcoma. We sought the causes of unexpected survival differences between the study groups.

Methods

647 patients were randomised. Cox regression analyses were used to compare event-free survival (EFS) and overall survival (OS) between the two study groups.

Results

5-year EFS rates were 43% (95% CI 36–50%) and 57% (95% CI 52–62) in the CCLG and GPOH patients, respectively; corresponding 5-year OS rates were 52% (95% CI 45–59%) and 66% (95% CI 61–71). CCLG patients were less likely to have both surgery and radiotherapy (18 vs. 59%), and more likely to have a single local therapy modality compared to the GPOH patients (72 vs. 35%). Forty-five percent of GPOH patients had pre-operative radiotherapy compared to 3% of CCLG patients. In the CCLG group local recurrence (either with or without metastases) was the first event in 22% of patients compared with 7% in the GPOH group. After allowing for the effects of age, metastases, primary site, histology and local treatment modality, the risk of an EFS event was 44% greater in the CCLG cohort (95% CI 10–89%, p = 0.009), and the risk of dying was 30% greater, but not statistically significant (95% CI 3–74%, p = 0.08).

Conclusions

Unexpected differences in EFS and OS occurred between two patient cohorts recruited within an international randomised trial. Failure to select or deliver appropriate local treatment modalities for Ewing's sarcoma may compromise chances of cure.

Trial registration Supported by Deutsche Krebshilfe (Grants No. DKH M43/92/Jü2 and DKH 70-2551 Jü3), and European Union Biomedicine and Health Programme (Grants No. BMH1-CT92-1341 and BMH4-983956), and Cancer Research United Kingdom. Clinical trial information can be found for the following: NCT0000251

https://ift.tt/2GkbzAh

Influence of fascicle length on twitch potentiation of the medial gastrocnemius across three ankle angles

Abstract

Purpose

Length dependence of post-activation potentiation (PAP) is a well-established phenomenon in animal models but less certain in intact whole human muscles. Recent advances in B-mode ultrasonography provide real-time imaging and evaluation of human muscle fascicles in vivo, thus removing the assumption that joint positioning alters fascicle length and influences the extent of PAP. The purpose of this study was to determine whether a conditioning maximal voluntary contraction (MVC) would influence the return of medial gastrocnemius (MG) fascicles to baseline length and alter the extent of twitch potentiation between three ankle positions.

Methods

Ultrasonography was used to measure MG fascicle length for baseline and potentiated twitches at angles of 10° dorsiflexion (DF), 0° neutral (NEU—tibia perpendicular to the sole of the foot), and 20° plantar flexion (PF). A MVC was used as a conditioning contraction and PAP determined for each ankle angle.

Results

PAP of the plantar flexors was greater in PF (28.8 ± 2.6%) compared to NEU (19.8 ± 1.8%; p < 0.05) and DF (9.3 ± 2.8%; p < 0.0001). In PF, fascicle lengths (4.64 ± 0.17 cm) were shorter than both NEU (5.78 ± 0.15 cm; p < 0.0001) and DF (6.09 ± 0.15 cm; p < 0.0001). Fascicle lengths for the baseline twitches were longer (5.92 ± 0.11 cm) than the potentiated twitches (5.83 ± 0.10 cm; p < 0.01) at all joint angles.

Conclusion

Although PAP is greatest in PF compared to NEU and DF, the higher PAP in the PF joint angle cannot be attributed to fascicles remaining shortened following the MVC because across all joint positions, fascicles are similarly shortened following the MVC.

https://ift.tt/2GiUFC6

Pathways to deliberative capacity: the role of the IPCC

Abstract

This article explores the arguments for expanding deliberation in the Intergovernmental Panel on Climate Change (IPCC) and scrutinizes their implications for the deliberative capacity of global environmental governance (GEG). An analysis of the IPCC is presented that builds on a systematic literature review and thus a broad set of scientific debates concerning the IPCC. Based on this analysis, two different paths are outlined, one moderate and one radical; these paths ascribe different democratizing functions to the IPCC and rely on different epistemologies. The moderate path emphasizes decision capacity, whereas the radical path strives to create deliberative space and to identify the value inherent in different claims. It is argued that the IPCC cannot accommodate the aspirations of these different pathways in a single assessment. Parallel assessments must be developed in complementary subject areas with different science-policy relations.

https://ift.tt/2pPq5VB

Planar hybrid carbon-decorated zinc oxide nanowires for infrared photodetection

Abstract

Vapor phase transport (VPT) assisted by thermal evaporation of methanol was utilized to favor the fabrication of hybrid carbon-decorated zinc oxide nanowires (C/ZnO NWs). The photoluminescence (PL) spectrum revealed evidence of optical properties for several defects such as zinc interstitials (Zn_i) and oxygen vacancy (V_o) in hybrid C/ZnO NWs. The PL also exhibited that the planar hybrid C/ZnO NWs photodetector has a wide range of sensitivity from ultraviolet (UV) to infrared (IR). The imaging results show formation of ZnO nanostructures which can be further confirmed from X-ray diffraction (XRD) results. XRD exhibits carbon (C)-related peaks at 12.88, 26, 43, 45, and 55° together with standard ZnO peaks. The incorporation of C shows excellent photoconduction towards varied laser powers (0.0, 7.82, 37.95, 69.20, 100.0, 130.0, and 160.0 mW) of IR illumination. The possibility of current drain in the device was evaluated based on the direct-current (DC) bias voltage of 0.00, 3.33, and 5.55 V. DC bias 3.33 and 5.55 V attributed increase of photocurrent towards the forward bias voltage. However, the reverse bias voltage illustrated a vast increase of photocurrent compared to the forward bias voltage. External quantum efficiency (EQE) at DC bias 5.55 V was 6.5–9.5 range folds greater than the EQE measured for zero bias voltage. Significant photoresponsivity was identical for various laser pulse ranging from 10 to 5000 Hz. Simultaneously, the rise (τ_r) and fall (τ_f) time were measured at 49 and 60.5 μs attributes that the fabrication technique can be improvised and implemented to enhance the efficiency of optoelectronic devices for future applications.

https://ift.tt/2E5sEI7

Predictive visual search: Role of environmental regularities in the learning of context cues

Abstract

Repeatedly searching through invariant spatial arrangements in visual search displays leads to the buildup of memory about these displays (contextual-cueing effect). In the present study, we investigate (1) whether contextual cueing is influenced by global statistical properties of the task and, if so, (2) whether these properties increase the overall strength (asymptotic level) or the temporal development (speed) of learning. Experiment 1a served as baseline against which we tested the effects of increased or decreased proportions of repeated relative to nonrepeated displays (Experiments 1b and 1c, respectively), thus manipulating the global statistical properties of search environments. Importantly, probability variations were achieved by manipulating the number of nonrepeated (baseline) displays so as to equate the total number of repeated displays across experiments. In Experiment 1d, repeated and nonrepeated displays were presented in longer streaks of trials, thus establishing a stable environment of sequences of repeated displays. Our results showed that the buildup of contextual cueing was expedited in the statistically rich Experiments 1b and 1d, relative to the baseline Experiment 1a. Further, contextual cueing was entirely absent when repeated displays occurred in the minority of trials (Experiment 1c). Together, these findings suggest that contextual cueing is modulated by observers' assumptions about the reliability of search environments.

https://ift.tt/2utEigp

Fragmented particles containing octreotide acetate prepared by spray drying technique for dry powder inhalation

Abstract

Dry powder inhalers (DPIs) have been proposed as an alternative administration route for protein and peptide drugs. However, DPI particles are easy to aggregate due to the strong interactions between the particles, leading to poor aerosolization performance. In this study, fragmented particles containing octreotide acetate (OA) were prepared by spray drying technique for dry powder inhalation, which were expected to decrease the particle-particle interaction by reducing the contact sites. Mannitol and ammonium carbonate were used as protein stabilizer and fragment-forming agent, respectively. The obtained fragmented particles presented larger particle size, lower density, better dispersibility, and well in vitro aerodynamic behavior (emitted dose > 97%, fine particle fraction ≈ 40%). The circular dichroism spectrum results indicated that OA maintained the stability throughout the spray drying process. The relative bioavailability of dry powder inhalation (DPI) compared with subcutaneous injection of commercial product was up to 88.0%, demonstrating the feasibility of DPI for OA delivery. These results confirmed that the proposed fragmented particles had great potential for pulmonary delivery of protein and peptide drugs in a painless, rapid, and convenient manner.

https://ift.tt/2IiBHIm

The histamine H4 receptor modulates the differentiation process of human monocyte-derived M1 macrophages and the release of CCL4/MIP-1β from fully differentiated M1 macrophages

Abstract

Objective

Histamine is an important mediator of biological functions and present in high amounts in inflammatory skin lesions which are characterised by a marked infiltration of myeloid derived cell populations. The aim of the study was to investigate the expression and function of histamine receptors, with a focus on the histamine H4 receptor (H4R) in detail during the differentiation process from monocytes to macrophages and on fully differentiated M1 macrophages.

Methods

Quantitative PCR, ELISA technique, and flow cytometry were applied to analyze expression levels of histamine receptors, of CXCL10, CCL4, CCL3, or IL-23 and of the macrophage differentiation marker CD68, respectively.

Results

We demonstrated that monocytes and fully differentiated M1 macrophages express H1R-, H2R-, and H4R mRNA which were differentially regulated during the differentiation process and in IFN-Ƴ and LPS classically activated M1 macrophages. The H3R mRNA was not expressed. During in vitro differentiation from monocytes to macrophages, the H4R agonist ST-1006 modified the M1 phenotype by up-regulating the macrophage differentiation marker CD68, by down-regulating the production of CXCL10, and by changing the morphology. In fully differentiated M1 macrophages, histamine or ST-1006 decreased the IFN-Ƴ- and LPS-induced CCL4 mRNA expression and protein production, whereas CCL3 or IL-23 production was not regulated via H4R.

Conclusions

We describe novel immunomodulatory functions of the H4R during the differentiation process of human monocyte-derived macrophages and in fully differentiated M1 macrophages. The down-regulation of Th1-related chemokines during the differentiation process or in classically activated macrophages via H4R may contribute to decreased migration of immune cells to the site of inflammation. This may have implications for the treatment of allergic diseases with H4R ligands regulating the dysbalance of Th2/Th1 polarizations in these disorders.

https://ift.tt/2J65OUj

Mini Gastric Bypass-One Anastomosis Gastric Bypass (MGB-OAGB)-IFSO Position Statement

Preamble

The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) has played an integral role in educating both the metabolic surgical and the medical community at large about the role of innovative and new surgical and/or endoscopic interventions in treating adiposity-based chronic diseases.

The mini gastric bypass is also known as the one anastomosis gastric bypass. The IFSO has agreed that the standard nomenclature should be the mini gastric bypass-one anastomosis gastric bypass (MGB-OAGB). The IFSO commissioned a task force (Appendix 1) to determine if MGB-OAGB is an effective and safe procedure and if it should be considered a surgical option for the treatment of obesity and metabolic diseases.

The following position statement is issued by the IFSO MGB-OAGB task force and approved by the IFSO Scientific Committee and Executive Board. This statement is based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence. It will be reviewed in 2 years.

https://ift.tt/2GiOPAp

Right trisegmentectomy after portal vein embolization in a high-risk toddler with hepatoblastoma

Abstract

Portal vein embolization (PVE) is a pre-operative treatment modality in adults undergoing hepatectomy with concerns of post-operative liver failure from insufficient future liver remnant (FLR). PVE induces growth in the FLR. The success of this technique is well described in adults, but not in young children with hepatoblastoma.

http://bit.ly/2GVyfE1

Radiation exposure for intraoperative 3D scans in a hybrid operating room: how to reduce radiation exposure for the surgical team

Abstract

Background

Hybrid operating rooms are used in different fields of surgery. In orthopedic surgery, the possibility of a 3D scan of difficult anatomical regions (spine, pelvis) showed promising results not only in navigated screw placement. The associated exposure to radiation raises questions regarding potential risks for the operating room personal and the patient. The present study focuses on scatter radiation during 3D scans in a hybrid operating room, the adjacent rooms, and methods to reduce radiation exposure.

Material and Methods

\(\hbox {RaySafe}^{\mathrm{TM}}\) i2 dosimeters were used to measure scatter radiation during 3D scans of different anatomical regions in different distances and heights in a hybrid operating room. The 3D scans were performed with a floor-based flat-panel robotic C-arm with 3D scan capability (Artis Zeego, Siemens; Germany). The 3D scans were performed using a human cadaver. The 3D scans were performed using a standard and a dose reduction protocol (DRP).

Results

The highest scatter radiation was measured during 3D scans of the pelvis on the side of the surgical assistant (39.5 Sv in height of 1 m) compared to the side of the main surgeon (23 Sv in height of 1 m). Scatter radiation was less on the position of the scrub nurse (6.8 Sv in height of 1 m) and during 3D scans of the other anatomical regions. The radiation dosage was about 66% less with the DRP. Low values of scatter radiation were measured behind a radiation protection wall and with open doors in the adjacent rooms.

Conclusion

While performing a scan scatter radiation was measured everywhere in the operating room especially during 3D scans of the pelvic girdle. Therefore, settings with lower dosage should be used whenever possible. Personnel should stand behind a radiation safety wall or leave the operating room and close the doors. For this study, six behavioral rules to avoid radiation in a hybrid operating room were established.

http://bit.ly/2E4g4c4

The responses of cucumber plants subjected to different salinity or fertilizer concentrations and reproductive success of Tetranychus urticae mites on these plants

Abstract

The plant stress hypothesis posits that a herbivore's reproductive success increases when it feeds on stressed plants, while the plant vigor hypothesis predicts that a herbivore preferentially feeds on more vigorous plants. We examined these opposing hypotheses by growing spider mites (Tetranychus urticae) on the leaves of stressed and healthy (vigorous) cucumber plants. Host plants were grown under controlled conditions at low, moderate, and high concentrations of NaCl (to induce salinity stress), at low, moderate, and high fertilizer concentrations (to support growth), and without these additions (control). The effects of these treatments were evaluated by measuring fresh and dry plant biomass, carotenoid and chlorophyll content, antioxidant enzyme activity, and concentrations of PO₄³⁻, K⁺, and Na⁺ in plant tissues. The addition of low concentrations of fertilizer increased dry mass, protein, and carotenoid content relative to controls, suggesting a beneficial effect on plants. The highest NaCl treatment (2560 mg L⁻¹) resulted in increased Na⁺ and protein content relative to control plants, as well as reduced PO₄³⁻, K⁺, and chlorophyll levels and reduced catalase and ascorbate peroxidase enzyme activity levels. Analysis of life table data of T. urticae mites raised on leaves from the aforementioned plant groups showed the intrinsic rate of increase (r) for mites was 0.167 day⁻¹ in control specimens, 0.125 day⁻¹ for mites reared on plants treated with a moderate concentration of fertilizer (10 mL L⁻¹), and was highest (0.241 day⁻¹) on plants grown under moderate salinity conditions (1920 mg L⁻¹ NaCl). Reproductive success of T. urticae did not differ on plants watered with a moderate concentration of NaCl or a high concentration of fertilizer. The moderately-stressed plants formed a favorable environment for the development and reproduction of spider mites, supporting the plant stress hypothesis.

http://bit.ly/2pOvZH1

Combined robot assisted right partial nephrectomy and cholecystectomy with single docking

Αbstract

We report the first case of robot-assisted partial nephrectomy (RARN) and Robot assisted cholecystectomy in a 66 years old female overweight patient with organ-confined right kidney tumor identified on the investigation of gastrointestinal symptoms with a single docking. A modified position of the patient and a slight altered placement of the trocars made feasible the concomitant performance of the two operations. Total blood loss was 80 ml, operation time was 253 min and console time 187 min. The drain was removed on second post-operative day and the patient was discharged at the 3rd post-operative day. Using a single docking of the da Vinci S system, intraoperative time and cost are minimized in patients with both organ-confined kidney tumors and gall bladder stones.

https://ift.tt/2GUAebF