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Rationale There is no agreed upon method for quantifying ventilation defect percentage (VDP) with high sensitivity and specificity from hyperpolarized (HP) gas ventilation MR images in multiple pulmonary diseases for both pediatrics and adults, yet identifying such methods will be necessary for future multi-site trials. Most HP gas MRI ventilation research focuses on a specific pulmonary disease and utilizes one quantification scheme for determining VDP. Here we sought to determine the potential of different methods for quantifying VDP from HP 129Xe images in multiple pulmonary diseases through comparison of the most utilized quantification schemes: linear binning and thresholding. Materials and Methods HP 129Xe MRI was performed in a total of 176 subjects (125 pediatrics and 51 adults, age 20.98±16.48 years) who were either healthy controls (n = 23) or clinically diagnosed with cystic fibrosis (CF) (n = 37), lymphangioleiomyomatosis (LAM) (n = 29), asthma (n = 22), systemic juvenile idiopathic arthritis (sJIA) (n = 11), interstitial lung disease (ILD) (n = 7), or were bone marrow transplant (BMT) recipients (n = 47). HP 129Xe ventilation images were acquired during a ≤16 second breath-hold using a 2D multi-slice gradient echo sequence on a 3T Philips scanner (TR/TE 8.0/4.0ms, FA 10-12°, FOV 300 × 300mm, voxel size≈3 × 3 × 15mm). Images were analyzed using 5 different methods to quantify VDPs: linear binning (histogram normalization with binning into 6 clusters) following either linear or a variant of a nonparametric nonuniform intensity normalization algorithm (N4ITK) bias-field correction, thresholding ≤60% of the mean signal intensity with linear bias-field correction, and thresholding ≤60% and ≤75% of the mean signal intensity following N4ITK bias-field correction. Spirometry was successfully obtained in 84% of subjects. Results All quantification schemes were able to label visually identifiable ventilation defects in similar regions within all subjects. The VDPs of control subjects were significantly lower (p Conclusion The difference in VDP between healthy controls and patients varied between the different disease states for all quantification methods. Although N4ITK bias-field corrected 60% thresholding was superior in separating the combined diseased group from controls, linear binning is able to better label low-ventilation regions unlike the current, 60% thresholding scheme. For future clinical trials, a consensus will need to be reached on which VDP scheme to utilize, as there are subtle advantages for each for specific disease.

Background: The purpose of this study is to present surgical outcomes after humeral head allograft augmentation and glenoid-based procedures in patients with active, uncontrolled seizure activity and anterior shoulder instability. Methods: A retrospective review of a surgical database for patients with active seizure disorder and with recurrent shoulder instability managed with humeral head augmentation was performed. All patients underwent surgical intervention. Postoperative outcomes including Shoulder Pain and Disability Index, Simple Shoulder Test, American Shoulder and Elbow Surgeons questionnaire, and the Short Form Health Survey (SF-12) were recorded at a minimum of 2 years. We hypothesized that appropriate management of the bony defects in these bipolar injuries would result in low recurrence and satisfactory outcomes. Results: Ten patients including 8 males and 2 females (15 shoulders) with active seizure-related shoulder instability underwent surgical intervention including allograft bone grafting of the Hill-Sachs lesion for anterior shoulder instability. The average age was 27 years. All patients reported recurrent seizures postoperatively, but only one sustained a shoulder dislocation after surgery that was unrelated to seizure activity.Self-reported satisfaction was “much better” or “better” in 92% of shoulders. Average outcome scores were as follows: American Shoulder and Elbow Surgeons score = 67 (33-100), Shoulder Pain and Disability Index = 32.5 (0-83), Simple Shoulder Test = 9.4 (5-12), SF-12 PCS = 44.1 (21-65), and SF-12 MCS = 50.6 (21-61). The average follow-up was 4.8 years. Conclusion: Management of bipolar shoulder injuries with humeral head allograft augmentation and glenoid based surgery leads to low recurrence rates and good clinical outcomes in patients with uncontrolled, seizure-related shoulder instability.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background: The Shoulder Pain and Disability Index (SPADI) is the most commonly used self-administered questionnaire which is a valid and reliable instrument to assess the proportion of pain and disability in shoulder disorders. There is no evidence of SPADI questionnaire being translated into regional Indian language (Marathi). Objective: This study aims to translate and culturally adapt and validate the Marathi version of the SPADI questionnaire. This was done as per the AAOS outcomes committee guidelines. Methods: Cross-cultural adaptation and psychometric testing of SPADI was done in the Outpatient Physiotherapy Department of Tertiary Care Hospital, Ahmednagar, India. Results: The internal consistency was assessed by calculating Cronbach alpha value for the pain score (0.908), disability score (0.959), and total SPADI (0.969) which were all high. The Test–retest reliability was assessed using the intraclass correlation coefficient (ICC) values for the pain score (0.993), disability score (0.997), and total SPADI (0.997) which showed excellent reliability. The criterion validity was assessed using Pearson correlation coefficient. In Males, weak to strong negative correlation was observed except for shoulder extension and in females, moderate negative correlation was observed between baseline shoulder range of motion and initial total SPADI scores and individual pain and disability except for shoulder internal rotation. The internal consistency of the Marathi SPADI (Cronbach’s alpha [Formula: see text]0.99) was higher than the original English version. The reliability of the total Marathi SPADI and its subscale (Intraclass correlation coefficient [Formula: see text]0.90) were found to be higher than that of the English SPADI and were consistent with the German, Brazilian, Slovene and Greek versions. Conclusion: The translated and culturally adapted Marathi version of the SPADI questionnaire is a reliable and valid tool for the assessment of pain and disability in Marathi population.

Policies intended to reduce the amount of greenhouse gas emissions are among the most hotly debated policy problems of our time. Among the concerns raised are that costs will be passed on to consumers and jobs will be lost. A vast economic literature has addressed the pricing of carbon dioxide, at least theoretically, but empirical evidence and observed market behavior following carbon legislation is scant due to the lack of policy implementation. We use the introduction and eventual tightening of the Regional Greenhouse Gas Initiative (RGGI), a regional carbon permit system in the Northeastern United States, to measure labor market responses and dynamics following the implementation of a carbon pricing system. We find that implementation of the RGGI and the subsequent tightening of the emissions cap has had no effect on employment or earnings in the utilities sector but increased the rate at which workers flow in and out of jobs. In particular, within the utilities sector, we observe some job destruction and worker separation combined with increased labor reallocation across establishments. This is complemented with small spillover effects yielding positive increases in hiring, worker reallocation and job creation in industries outside of utilities. Furthermore, when we account for the endogeneity of electricity prices we fi nd increased hiring, job creation and worker reallocation rates and a decline in job destruction rates across industries.

Objective Adult polyglucosan body disease (APBD) is an adult‐onset neurological variant of glycogen storage disease type IV. APBD is caused by recessive mutations in the glycogen branching enzyme gene, and the consequent accumulation of poorly branched glycogen aggregates called polyglucosan bodies in the nervous system. There are presently no treatments for APBD. Here, we test whether downregulation of glycogen synthesis is therapeutic in a mouse model of the disease. Methods We characterized the effects of knocking out two pro‐glycogenic proteins in an APBD mouse model. APBD mice were crossed with mice deficient in glycogen synthase (GYS1), or mice deficient in protein phosphatase 1 regulatory subunit 3C (PPP1R3C), a protein involved in the activation of GYS1. Phenotypic and histological parameters were analyzed and glycogen was quantified. Results APBD mice deficient in GYS1 or PPP1R3C demonstrated improvements in life span, morphology, and behavioral assays of neuromuscular function. Histological analysis revealed a reduction in polyglucosan body accumulation and of astro‐ and micro‐gliosis in the brains of GYS1‐ and PPP1R3C‐deficient APBD mice. Brain glycogen quantification confirmed the reduction in abnormal glycogen accumulation. Analysis of skeletal muscle, heart, and liver found that GYS1 deficiency reduced polyglucosan body accumulation in all three tissues and PPP1R3C knockout reduced skeletal muscle polyglucosan bodies. Interpretation GYS1 and PPP1R3C are effective therapeutic targets in the APBD mouse model. These findings represent a critical step toward the development of a treatment for APBD and potentially other glycogen storage disease type IV patients.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence. Objective: To present the results from the APCCC 2019. Design, setting, and participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naive prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process. Results and limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material. Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.

NEW FINDINGS What is the central question of this study? Is the estrous cycle affected during disuse atrophies and if so, how do estrous cycle changes relate to musculoskeletal outcomes? What is the main finding and its importance? Rodent estrous cycles are altered during disuse atrophy, which corresponds to musculoskeletal outcomes. However, the estrous cycle does not appear changed in Lewis Lung Carcinoma, which corresponded to no differences in muscle size compared to healthy controls. These findings suggest a relationship between estrous cycle and muscle size during atrophic pathologies. ABSTRACT Hyperglycemia can cause disruptions in vascular function, whereas exercise has been shown to restore vascular function. The primary aim of this study is to investigate the effect of performing whole-body resistance exercise, 30-min before, immediately following, or 30- or 60-min after a high carbohydrate meal, on endothelial function, measured by flow-mediated dilation (FMD). Healthy adults will be recruited to this randomized crossover trial to compare the postprandial glycaemic and vascular responses to four different exercise timing conditions and a control: i) C- control, high carbohydrate meal/no exercise, ii) 30Pre- 30 min of resistance exercises (~30% of 1RM [Repetition Maximum]), 30 min before a high carbohydrate meal, iii) IP- 30 min of resistance exercises (~30% of 1RM), immediately following a high carbohydrate meal, iv) 30Post- 30 min of resistance exercises, 30 min after a high carbohydrate meal and v) 60Post- 30 min of resistance exercises, 60 min after a high carbohydrate meal. Measures of metabolic and vascular function will be assessed at baseline and for two hours following the carbohydrate-based breakfast meal.

Initial assessments of coronavirus disease 2019 (COVID-19) preparedness revealed resource shortages and variations in infection prevention policies across US hospitals. Our follow-up survey revealed improvement in resource availability, increase in testing capacity, and uniformity in infection prevention policies. Most importantly, the survey highlighted an increase in staffing shortages and use of travel nursing.

BACKGROUND LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. OBJECTIVES This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. METHODS We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. RESULTS This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P

BACKGROUND: Despite therapeutic advances for patients with schizophrenia, improving patient outcomes and reducing the cost of care continue to challenge formulary decision makers. OBJECTIVES: To (1) understand the perspectives of formulary decision makers on challenges to optimal schizophrenia population management and (2) identify best practices and recommendations for mitigating these challenges. METHODS: This mixed-methods study, conducted in a double-blind manner, comprised in-depth telephone interviews with formulary decision makers from February through May 2020, and a web-based follow-on survey that was sent to all participants in October 2020. US-based formulary decision makers were recruited if they were directly involved in schizophrenia drug formulary or coverage decision making for national or regional payers, health systems, or behavioral health centers. Formulary decision makers' perceptions of challenges, policies, and programs related to schizophrenia population health management were assessed generally and in the context of the COVID-19 pandemic. RESULTS: 19 formulary decision makers participated in the interviews and 18 (95%) completed the survey. Participants reported a spectrum of patient- and payer-driven challenges in schizophrenia population health management, including medication nonadherence, high pharmacy and medical costs, and frequent hospitalizations and emergency department visits. Participants noted that COVID-19 had worsened all identified challenges, although patient unemployment (mean score of 2.00 on a scale of 1 [made much worse] to 5 [made much better]) and reduced access to psychiatric care (mean score, 2.12) were most negatively affected. The most common strategies implemented in order to improve schizophrenia population health management included case management (89%), telemedicine (83%), care coordination programs (72%), strategies to mitigate barriers to accessing medication (61%), and providing nonmedical services to address social determinants of health (56%). Participants noted that, ideally, all treatments for schizophrenia would be available on their formularies without utilization management policies in place in order to increase accessibility to medication, but cost to the health plans made that difficult. Whereas 61% of respondents believed that long-acting injectable antipsychotics (LAIs) were currently underused in their organizations, only 28% represented organizations with open access policies for LAIs. Participants believed that among patients with schizophrenia, LAIs were most beneficial for those with a history of poor or uncertain adherence to oral medications (mean score of 4.50 on a scale of 1 [not at all beneficial] to 5 [extremely beneficial]) and those with recurring emergency department visits and inpatient stays (mean score, 3.94). Study participants reported slightly increased use of LAIs (mean score of 3.17 on a scale of 1 [negatively impacted] to 5 [positively impacted]) among their patients with schizophrenia in response to the COVID-19 pandemic; 29% of participants reported easing access restrictions for LAIs. CONCLUSIONS: Participants described persisting challenges and various approaches intended to improve schizophrenia population health management. They also recommended strategies to optimize future health management for this population, including expanding programs to address social determinants of health and mitigating barriers to accessing treatment. DISCLOSURES: This study was funded by Janssen Scientific Affairs, LLC. Roach, Graf, Pednekar, and Chou are employees of PRECISIONheor, which received financial support from Janssen Scientific Affairs, LLC, to conduct this study. Chou owns equity in Precision Medicine Group, the parent company of PRECISIONheor. Lin and Benson are employees of Janssen Scientific Affairs, LLC. Doshi has served as a consultant, advisory board member, or both, for Acadia, Allergan, Boehringer Ingelheim, Janssen, Merck, Otsuka, and Sage Therapeutics and has received research funding from AbbVie, Biogen, Humana, Janssen, Novartis, Merck, Pfizer, PhRMA, Regeneron, Sanofi, and Valeant.

OBJECTIVE. Knee osteoarthritis (OA) is a leading source of pain and disability among older adults. Self-management (SM) strategies are recommended to manage OA symptoms. Sociodemographic and clinical characteristics, along with other factors, may influence SM utilization rate. This study sought to examine the prevalence and correlates of SM use for pain among non-Hispanic Black patients (NHB) and non-Hispanic White patients (NHW) older adults with or at risk for knee OA. METHODS. A secondary data analysis was conducted on the Understanding Pain and Limitations in Osteoarthritic Disease multisite observational study, which included NHB (n = 104) and NHW (n = 98) community-dwelling older adults with or at risk for knee OA. Participants completed measures of sociodemographics, pain SM use, coping, and clinical and experimental pain. RESULTS. Clinical and experimental pain were significantly greater among NHBs compared to NHWs. There were no significant differences in use of total SM by ethnicity/race. Interestingly, multiple linear regression revealed that clinical and experimental pain indices, as well as coping, number of pain sites, age, and sex were differentially associated with total SM use between NHBs and NHWs. There were significant ethnicity/race by type of pain management interaction effects for pain measures. CONCLUSION. SM is common among older adults with or at risk for knee OA pain, and the prevalence of SM does not differ by ethnicity/race, but many guideline-recommended interventions for OA are underutilized. Importantly, different factors were associated with the use of SM, highlighting distinct biopsychosocial mechanisms contributing to SM use in NHBs and NHWs.

The gate material work function engineering and hetero-dielectric engineering concepts are discussed in this paper to design a novel triple material DG Tunnel FET. The three different work functions and the hetero-dielectric material within the transistor control the charge carrier density in the source, drain, and channel region. The heterojunction germanium and silicon material in the source-channel junction improve tunneling based on the bandgap engineering. The hetero-dielectric materials, namely high–K material in the source region and low-K material in the drain region, suppress the gate-to-drain capacitance effect, enhancing the cut-off frequency. The increased tunneling enhances the ON current, and the tri material restricts the reverse tunneling, which suppresses the ambipolar behaviour of the TFET. The electrical characteristics like surface potential, electric field, drain current, transconductance, and cut-off frequency of the TMDG TFET are simulated using TCAD simulation. Also, results validate the suitable selection of the doping concentration in the source, drain region and different tri-gate work function values for the proposed TMDG TFET. The proposed device shows remarkable progress in ON current of the order (10− 3 A/µm) and the leakage current in Femto range (10− 17 A/µm), with the ION/IOFF current ratio of 1014. The proposed structure is suitable for low-power applications.

The work was supported by funding from King Abdullah University of Science and Technology (KAUST).

Background The purpose of this study was to determine if addition of CT to axillary radiographs (AXR) alters preoperative decision making for shoulder arthroplasty. Methods Preoperative deidentified images (XR alone and XR with CT) of 50 patients with glenohumeral arthritis were reviewed independently by 3 reviewers in a blinded fashion. Each reviewer graded images for glenoid wear pattern as simple (Walch A1 or B1) or advanced [A2, B2, C]), adequacy of AXR and need for advanced imaging. The reviewers determined a preoperative plan for all patients based on XR alone vs. XR and CT including the arthroplasty type (anatomic or reverse total shoulder) and their plan for treating glenoid wear (eccentric or standard reaming vs. bone graft or augment). Kappa values (κ) were calculated to determine inter-rater agreement and consistency among multiple reviewers. Fisher's exact test was used to assess any difference in preoperative plan once the shoulders were separated into simple and advanced glenoid wear patterns. Results The 3 reviewers agreed that quality of AXRs was significantly inadequate (P Conclusion Axillary radiographs are often inadequate for preoperative planning in shoulder arthritis with advanced glenoid wear patterns (Walch A2, B2, C types). Addition of CT imaging to radiographs in shoulder arthritis with advanced glenoid wear can affect the preoperative decision with respect to type of shoulder arthroplasty and/or plan for addressing glenoid wear (reaming, bone graft or augmented glenoids). Level of evidence Level IV

Mitral valve repair is infrequently performed in patients undergoing corrective surgery for failed mitral transcatheter edge-to-edge repair in current United States practice. This article describes surgical techniques for reconstructive surgery after failed transcatheter edge-to-edge repair. Nine patients underwent robotic-assisted mitral surgery after failed transcatheter edge-to-edge repair between 2008 and 2020 at a single center. Repair was completed in 88.9% (n = 8) patients, and freedom from2+ mitral regurgitation was 87.5% (n = 7) at a median follow-up of 1.9 years.

Despite the increase in efforts to attract and retain international students in Canada, including the introduction of the Canadian Experience Class in 2008, there has been little investigation into what supports will assist international students as they transition from students to workers to migrants. This research paper is a Toronto-based investigation of the service needs and gaps that exist for international students aiming to transition to permanent residency in Canada. Data gathered from interviews with front-line workers assisting international students, an immigrant-serving organization, and government suggests that immigration policy reforms aiming to attract and retain international students have not been accompanied by the necessary changes to traditional settlement and international student services resulting in service gaps for this segment of Canada's international student population. The present study also connects these findings to neoliberal immigration policies and practices in place in Canada since the 1990s.

Ovarian cancer is the seventh most common cancer among women and a leading cause of death from gynaecological malignancies. Epithelial ovarian cancer is the most common type, accounting for around 90% of all ovarian cancers. This specific type of ovarian cancer starts in the surface layer covering the ovary or lining of the fallopian tube. Surgery is performed either before chemotherapy (upfront or primary debulking surgery (PDS)) or in the middle of a course of treatment with chemotherapy (neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS)), with the aim of removing all visible tumour and achieving no macroscopic residual disease (NMRD). The aim of this review is to investigate the prognostic impact of size of residual disease nodules (RD) in women who received upfront or interval cytoreductive surgery for advanced (stage III and IV) epithelial ovarian cancer (EOC).To assess the prognostic impact of residual disease after primary surgery on survival outcomes for advanced (stage III and IV) epithelial ovarian cancer. In separate analyses, primary surgery included both upfront primary debulking surgery (PDS) followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval debulking surgery (IDS). Each residual disease threshold is considered as a separate prognostic factor.We searched CENTRAL (2021, Issue 8), MEDLINE via Ovid (to 30 August 2021) and Embase via Ovid (to 30 August 2021).We included survival data from studies of at least 100 women with advanced EOC after primary surgery. Residual disease was assessed as a prognostic factor in multivariate prognostic models. We excluded studies that reported fewer than 100 women, women with concurrent malignancies or studies that only reported unadjusted results. Women were included into two distinct groups: those who received PDS followed by platinum-based chemotherapy and those who received IDS, analysed separately. We included studies that reported all RD thresholds after surgery, but the main thresholds of interest were microscopic RD (labelled NMRD), RD 0.1 cm to 1 cm (small-volume residual disease (SVRD)) and RD1 cm (large-volume residual disease (LVRD)).Two review authors independently abstracted data and assessed risk of bias. Where possible, we synthesised the data in meta-analysis. To assess the adequacy of adjustment factors used in multivariate Cox models, we used the 'adjustment for other prognostic factors' and 'statistical analysis and reporting' domains of the quality in prognosis studies (QUIPS) tool. We also made judgements about the certainty of the evidence for each outcome in the main comparisons, using GRADE. We examined differences between FIGO stages III and IV for different thresholds of RD after primary surgery. We considered factors such as age, grade, length of follow-up, type and experience of surgeon, and type of surgery in the interpretation of any heterogeneity. We also performed sensitivity analyses that distinguished between studies that included NMRD in RD categories of1 cm and those that did not. This was applicable to comparisons involving RD1 cm with the exception of RD1 cm versus NMRD. We evaluated women undergoing PDS and IDS in separate analyses.We found 46 studies reporting multivariate prognostic analyses, including RD as a prognostic factor, which met our inclusion criteria: 22,376 women who underwent PDS and 3697 who underwent IDS, all with varying levels of RD. While we identified a range of different RD thresholds, we mainly report on comparisons that are the focus of a key area of clinical uncertainty (involving NMRD, SVRD and LVRD). The comparison involving any visible disease (RD0 cm) and NMRD was also important. SVRD versus NMRD in a PDS setting In PDS studies, most showed an increased risk of death in all RD groups when those with macroscopic RD (MRD) were compared to NMRD. Women who had SVRD after PDS had more than twice the risk of death compared to women with NMRD (hazard ratio (HR) 2.03, 95% confidence interval (CI) 1.80 to 2.29; IIn a PDS setting, there is moderate-certainty evidence that the amount of RD after primary surgery is a prognostic factor for overall and progression-free survival in women with advanced ovarian cancer. We separated our analysis into three distinct categories for the survival outcome including NMRD, SVRD and LVRD. After IDS, there may be only two categories required, although this is based on very low-certainty evidence, as all but one study included NMRD in the SVRD category. The one study that separated NMRD from SVRD showed no improved survival outcome in the SVRD category, compared to LVRD. Further low-certainty evidence also supported restricting to two categories, where women who had any amount of MRD after IDS had a significantly greater risk of death compared to women with NMRD. Therefore, the evidence presented in this review cannot conclude that using three categories applies in an IDS setting (very low-certainty evidence), as was supported for PDS (which has convincing moderate-certainty evidence).

Background: Pseudomonas aeruginosa is one of the most commonly encountered gram-negative aerobic bacilli in the differential diagnosis of several probable hospital-acquired infections. Hence, the present study is designed to determine the Pseudomonas positivity and sensitivity in Invasive bloodstream infections using automated Bactec systems as the Antibiotic Sensitivity Profiles differ from one clinical setting to another. Material and Methods: All the blood culture samples received in the Department of Microbiology for culture by Bactec Bd fx from July 2015 to June 2016 were included in the study. The blood culture was observed in the Bactec bd fx system for at least 5 days before they are reported as sterile. Results: Among the total 1275 cultures which were positive for bacteria, 931(73.02%) were positive for gram-negative bacteria. Among the total of 931culture which were positive for gram-negative bacteria, Pseudomonas aeruginosa was isolated in 120(12.89%) cultures. Maximum was found in the age group of 0-1 years 33(27.50%) followed by 19-45 years 26(21.67%). Pseudomonas spp isolates were 100.00% sensitive to Colistin followed by Levofloxacin 84.44%, Piperacillin Tazobactum 82.50%, PB 77.50%, Amikacin 75.00%, Cefepime 75.00% while Pseudomonas spp isolates were 90% resistant to Ampicillin followed by Ceftazidime clavulanic acid 82.64% and Aztreonam 70.31%. Conclusion: Pseudomonas aeruginosa is one of the most common organisms among Gram-Negative isolates and the most commonly isolated in the neonate and infant age group. All the Pseudomonas isolates showed maximum sensitivity to Colistin followed by Levofloxacin, Piperacillin Tazobactum, Amikacin while they were most resistant to Ampicillin followed by Ceftazidime clavulanic acid and Aztreonam. Some alternative novel techniques need to be developed to counter the increasing menace of antibiotic resistance in this particular pathogenic bacteria

Background: Bicytopenia and Pancytopenia are relatively common presentations in adults as compared to paediatric patients. Clinical features present in different manifestations in children with Pancytopenia/Bicytopenia, which can range from bone marrow suppression temporarily to marrow infiltration by life-threatening malignancies. Aim: To study the clinical and haematological profile in the paediatric age group withCytopenias. The study aims to analyze the severity of hematological findings as per causative factors in patients with Pancytopenia and Bicytopenia. Methods: Prospective Observational Study conducted in the Department of Paediatrics in Dr.RPGMC Tanda Himachal Pradesh (INDIA). The study included all patients except those falling in the exclusion criteria.It was performed after oral and written informed consent.A total of 50 children admitted with bicytopenia and pancytopenia were enrolled from March 2013 to March 2014. Results: Infection was the commonest etiology observed in 22(44%) patients with bicytopenia and pancytopenia. Bicytopenia was seen in 14 (20%) and pancytopenia in 8 (16%) cases with infection. Scrub typhus was the commonest Infection seen in 18(32%).Leukaemia was notedin 11(22%) cases. Conclusions: The commonest age group affected was 11-15 years with female domination with a Male: Female ratio of 0.78:1. The commonest symptom was fever 37(74%) then generalized weakness in 29 (58%) cases.Pallor was the most common sign in 43(86%) followed by Hepatomegaly 32(64%), Lymphadenopathy 30(60%), and Splenomeagly in 29 (58%) patients. Infection was the commonest etiology followed by leukemia and megaloblastic anaemia. Scrub typhus was the commonest infection encountered in the present study.

In general, Natural Language Processing (NLP) algorithms exhibit black-box behavior. Users input text and output are provided with no explanation of how the results are obtained. In order to increase understanding and trust, users value transparent processing which may explain derived results and enable understanding of the underlying routines. Many approaches take an opaque approach by default when designing NLP tools and do not incorporate a means to steer and manipulate the intermediate NLP steps. We present an interactive, customizable, visual framework that enables users to observe and participate in the NLP pipeline processes, explicitly manipulate the parameters of each step, and explore the result visually based on user preferences. The visible NLP (VNLP) pipeline design is then applied to a text similarity application to demonstrate the utility and advantages of a visible and transparent NLP pipeline in supporting users to understand and justify both the process and results. We also report feedback on our framework from a modern languages expert.

Background Liver biopsy used to be the gold standard to assess liver fibrosis in patients infected with hepatitis C virus (HCV). Nonetheless, due to its invasive nature, techniques such as transient elastography liver stiffness (TE-LS), fibrosis index based on four factors (FIB-4) and aspartate transaminase-to-platelet ratio index (APRI) scores are currently being used. FIB-4 and APRI scores have the advantage of low cost and are readily available, compared with TE-LS. Herein, we evaluated the diagnostic performance of these scoring systems as compared to TE-LS in assessing liver fibrosis in patients with human immunodeficiency virus (HIV) and HCV co-infection. Methods The medical records of patients with HIV and HCV co-infection who had TE-LS done at our facility between August 1, 2013 and January 1, 2020 were extracted and analyzed. Exclusion criteria include: 1) patients co-infected with hepatitis B virus; 2) invalid TE-LS assessment; 3) have ≥ 10th upper limit of normal (ULN) alanine aminotransferase (ALT) levels; and 4) excessive alcohol use. Patient demographics, medical history, biochemical and clinical data were retrieved. For each patient, we calculated the FIB-4 and APRI score. Descriptive analysis was performed and correlation of FIB-4 and APRI with TE-LS was assessed with GraphPad Prism statistical software. Results Five hundred forty-seven patients underwent TE-LS during the study period. After excluding those without complete laboratory parameters, the total study population was 344. Their age was 56 ± 10.4 years and 234 (68%) were male. The average aspartate aminotransferase (AST) and ALT were 27.95 and 30.73. The average platelet count was 224 and the average TE-LS was 7.29. Fourteen patients (4.1%) had TE-LS values between 9 and 11.9 kPa and were classified as F3, while 29 (8.5%) had TE-LS ≥ 12 kPa and were classified as F4. With the correlation analysis, both APRI (correlation coefficient, r = 0.1097, 95% confidence interval (CI) 0.0403 - 0.2130; P = 0.042) and FIB-4 (r = 0.0424, 95% CI -0.0634 - 0.1474; P = 0.4335) were not correlated with TE-LS stages of fibrosis. Conclusion In our cohort, we failed to demonstrate that APRI and FIB-4 are reliable alternatives for screening liver fibrosis in patients with HIV and HCV co-infection. Nonetheless, APRI score still has a potential role as a screening tool instead of TE-LS measurement, which is costly and not readily available. It will be important to corroborate these findings in another large cohort, since this may have an important impact on patient management.

Sleep loss causes mood disturbance in non-clinical populations under severe conditions, i.e., two days/nights of sleep deprivation or a week of sleep restriction with 4–5 h in bed each night. However, the effects of more-common types of sleep loss on mood disturbance are not yet known. Therefore, the aim of this study was to examine mood disturbance in healthy adults over a week with nightly time in bed controlled at 5, 6, 7, 8 or 9 h. Participants (n = 115) spent nine nights in the laboratory and were given either 5, 6, 7, 8 or 9 h in bed over seven consecutive nights. Mood was assessed daily using the Profile of Mood States (POMS-2). Mixed-linear effects models examined the effect of time in bed on total mood disturbance and subscales of anger-hostility, confusion-bewilderment, depression-dejection, fatigue-inertia, tension-anxiety, vigour-activity and friendliness. There was no effect of time in bed on total mood disturbance (F(4, 110.42) = 1.31, p = 0.271) or any of the subscales except fatigue-inertia. Fatigue-inertia was higher in the 5 h compared with the 9 h time in bed condition (p = 0.012, d = 0.75). Consecutive nights of moderate sleep loss (i.e., 5–7 h) does not affect mood but does increase fatigue in healthy males.

Background: Research that identifies and celebrates the positive attributes of women educational leaders advancing a social justice agenda in traditionally male-dominated, Sub-Saharan African (SSA) societies is sparse. Studying female educational leadership in SSA conceptually brings to the fore issues associated with the intersectionality of gender, leadership, pervasive abject poverty, and cultural mores from a critical theory lens that runs counter to the White, western, male conceptions of leadership underlying much of the existing literature in the field. Purpose: With a focus on Ethiopia, we sought to understand the way in which women educational leaders, as traditionally oppressed groups in a patriarchal society, utilize their past marginalization as they advance a social justice agenda to promote educational opportunities for traditionally underserved students, particularly females. Research Design: Using transformative leadership as our theoretical lens and semi-structured interviews as our methodology, we conducted a grounded phenomenological study of eight Ethiopian women who were in educational leadership positions ranging from assistant principal to regional supervisors. We recruited the women leaders through direct contact, reputational nomination, and leadership positions they held. Findings/Results: Our findings paint a portrait of these female leaders as tenacious and determined, with a strong sense of self-agency and moral courage, whose identities are born out of their humble beginning and multi-focal understanding of issues from being female, from poor communities, submersed in male-dominated culture. These identities drove the participants to work towards emancipatory policies to acknowledge and intervene in “power differences” that directly influence school performance for girls and women in Ethiopia. Conclusions/Recommendations: Increasing workforce diversity with respect to gender, recasting leadership preparation programs as equity-oriented institutions, and addressing key public policies to support women in leadership positions are foundational recommendations that can lead to gender equity in education in Ethiopia.

The rapid development and roll-out of coronavirus disease 2019 (COVID-19) vaccines is providing hope for a way to control the pandemic. As pregnant and lactating women are generally excluded from clinical trials, the vaccination programme was launched without adequate safety and efficacy data for pregnant women. Yet many professional organizations have recognized the need for administration of COVID-19 vaccines in pregnancy and have issued their own set of recommendations. The lack of evidence, however, has often led to confused messaging, inconsistent language and differing recommendations across organizations, potentially contributing to delay or refusal to accept vaccination by pregnant women. We summarize those differences and recommend that leaders collaborate at a country level to produce joint recommendations. We use the example of Australia, where two professional authorities along with the government and partners in New Zealand worked towards one message, consistent language and a unified recommendation. The aim was to help health professionals and women who are planning pregnancy or who are currently pregnant or breastfeeding to make an informed decision about COVID-19 vaccination. National advisory groups for immunization, professional obstetric organizations and government bodies should be encouraged to coordinate their statements on COVID-19 vaccination for pregnant and lactating women and to use similar language and phrasing for greater clarity.La rapidité de développement et de déploiement des vaccins contre la maladie à coronavirus 2019 (COVID-19) entretient l'espoir d'un jour pouvoir contrôler la pandémie. Étant donné que les femmes enceintes et allaitantes sont généralement exclues des essais cliniques, le programme de vaccination a été lancé en l'absence de données adéquates sur l'efficacité et l'innocuité du vaccin au sein de cette catégorie. Pourtant, de nombreuses associations professionnelles ont reconnu la nécessité de vacciner contre la COVID-19 durant la grossesse, et ont émis leurs propres recommandations. L'absence de preuves a toutefois souvent donné lieu à une communication incohérente, à un discours contradictoire et à des recommandations divergentes d'une organisation à l'autre, ce qui pourrait avoir conduit certaines femmes enceintes à retarder ou refuser la vaccination. Dans le présent document, nous exposons ces différences et exhortons les dirigeants à collaborer au niveau national pour formuler des recommandations communes. Nous utilisons l'exemple de l'Australie, où deux autorités professionnelles ont travaillé avec le gouvernement et des partenaires en Nouvelle-Zélande afin de transmettre un message unique, d'adopter un langage cohérent et de fournir des directives homogènes. L'objectif était d'aider les soignants et les femmes enceintes, allaitantes ou planifiant une grossesse à prendre une décision éclairée en matière de vaccination contre la COVID-19. Les organes consultatifs nationaux sur la vaccination, les associations professionnelles d'obstétrique et les pouvoirs publics devraient être encouragés à aligner leurs déclarations concernant la vaccination contre la COVID-19 chez les femmes enceintes et allaitantes, ainsi qu'à employer des termes et énoncés similaires pour davantage de clarté.El rápido desarrollo y puesta en marcha de las vacunas contra el coronavirus de la enfermedad por coronavirus (COVID-19) está dando esperanzas sobre una forma de controlar la pandemia. Como las mujeres embarazadas y lactantes suelen estar excluidas de los ensayos clínicos, el programa de vacunación se puso en marcha sin datos adecuados de seguridad y eficacia para las mujeres embarazadas. Sin embargo, muchas organizaciones profesionales han reconocido la necesidad de administrar las vacunas contra la COVID-19 durante el embarazo y han emitido su propio conjunto de recomendaciones. Sin embargo, la falta de pruebas a menudo ha ocasionado mensajes confusos, un lenguaje incoherente y recomendaciones diferentes en las distintas organizaciones, lo que puede contribuir a retrasar o rechazar la vacunación de las mujeres embarazadas. Resumimos esas diferencias y recomendamos que los líderes colaboren a nivel de país para elaborar recomendaciones conjuntas. Utilizamos el ejemplo de Australia, donde dos autoridades profesionales, junto con el gobierno y los socios de Nueva Zelanda, trabajaron para lograr transmitir un único mensaje con un lenguaje coherente y una recomendación unificada. El objetivo era ayudar a los profesionales sanitarios y a las mujeres que planean un embarazo o embarazadas o en periodo de lactancia a tomar una decisión informada sobre la vacunación contra la COVID-19. Hay que animar a los grupos consultivos nacionales de inmunización, a las organizaciones profesionales de obstetricia y a los organismos gubernamentales a que coordinen sus declaraciones sobre la vacunación contra la COVID-19 para las mujeres embarazadas y lactantes y a que utilicen un lenguaje y una redacción similares para mayor claridad.إن التطور والطرح السريع للقاحات مرض فيروس كورونا 2019 (كوفيد 19)، يمنحان الأمل في توفير طريقة للسيطرة على الجائحة. ونظرًا لأن النساء الحوامل والمرضعات يتم استبعادهن عمومًا من التجارب الإكلينيكية، فقد تم إطلاق برنامج التطعيم دون توفر بيانات كافية عن السلامة والفعالية بالنسبة للحوامل. إلا أن العديد من المنظمات المهنية قد أدركت الحاجة إلى إعطاء لقاحات كوفيد 19 أثناء الحمل، وأصدرت مجموعة من التوصيات الخاصة بها. ومع ذلك، فقد أدى الافتقار لوجود أدلة في كثير من الأحيان إلى رسائل مربكة، ولغة غير متناغمة، وتوصيات مختلفة من المنظمات المختلفة، وهو ما قد يساهم في تأخير أو رفض قبول التطعيم من جانب النساء الحوامل. نحن نلخص هذه الاختلافات، ونوصي بأن يقوم القادة بالتعاون على مستوى الدولة لوضع توصيات مشتركة. نحن نستخدم المثال الخاص بأستراليا، حيث عملت سلطتان مهنيتان، جنبًا إلى جنب، مع الحكومة، والشركاء في نيوزيلندا معًا، من أجل صياغة رسالة واحدة، ولغة متناغمة، وتوصية موحدة. كان الهدف هو مساعدة أخصائيي الصحة والنساء اللواتي يخططن للحمل، أو الحوامل أو المرضعات حاليًا، لاتخاذ قرار مستنير بشأن تطعيم كوفيد 19. يجب تشجيع المجموعات الاستشارية الوطنية للتحصين، ومنظمات التوليد المهنية، والهيئات الحكومية على تنسيق بياناتها بشأن تطعيم كوفيد 19 للنساء الحوامل والمرضعات، واستخدام لغة وصياغة مماثلة لتحقيق مزيد من الوضوح.新型冠状病毒肺炎疫苗的快速研发和推广为疫情防控工作带来了希望。由于临床试验通常不纳入孕期和哺乳期妇女,所以疫苗接种计划的推行并没有充足的针对孕期妇女的安全和疗效数据。不过,众多专业组织已经意识到在孕期接种新冠疫苗的必要性,并且发布了自己的一套推荐程序。然而,证据的缺乏往往导致不同组织之间的信息混乱、语言不一致和意见分歧,从而有可能导致孕妇推迟或拒绝接种疫苗。我们总结了这些差异并建议各个组织的领导能够在国家层面开展合作以提出意见统一的推荐程序。我们以澳大利亚为例,该国两个专业的权威机构与政府和新西兰的合作伙伴联合提出以一致的语言,传递统一的讯息和推荐程序。其目的在于帮助医护工作者和打算怀孕或者正处于孕期或哺乳期的妇女针对新冠疫苗接种作出明智的决策。我们应鼓励国家免疫咨询小组、专业的产科机构和政府单位统一他们针对孕期和哺乳期妇女接种新冠疫苗方面的陈述,并使用类似的语言和措辞以便更加明确地阐述其意见。.Быстрая разработка и внедрение вакцин против коронавирусной инфекции 2019 года (COVID-19) вселяет надежду в борьбе с этой пандемией. Поскольку беременные и кормящие женщины обычно не участвуют в клинических испытаниях, программа вакцинации была запущена без надлежащих данных о безопасности и эффективности для беременных женщин. Тем не менее многие профессиональные организации признали необходимость применения вакцины против COVID-19 во время беременности и выпустили свой собственный набор рекомендаций. Однако отсутствие доказательств часто приводило к путанице в информационных сообщениях, противоречащим формулировкам и несогласованным рекомендациям в разных организациях, что потенциально способствовало задержке вакцинации или отказу беременных женщин от вакцинации. Авторы приводят сводку этих различий и рекомендуют руководителям сотрудничать на уровне страны для подготовки совместных рекомендаций. В качестве примера использован опыт Австралии, где два профессиональных органа вместе с правительством и партнерами в Новой Зеландии работали над согласованным информированием, едиными формулировками и рекомендациями. Цель заключалась в том, чтобы помочь медицинским работникам и женщинам, планирующим беременность, беременным или кормящим грудью, принять обоснованное решение по поводу вакцинации против COVID-19. Следует поощрять национальные консультативные группы по иммунизации, профессиональные акушерские организации и государственные органы согласовывать свои заявления о вакцинации против COVID-19 для беременных и кормящих женщин, а также использовать схожие формулировки и выражения для обеспечения большей ясности.

Background Survival, functional outcomes, and quality of life after left ventricular assist device (LVAD) are ill-defined in elderly patients, and with new-generation devices. Objectives This study sought to evaluate survival, functional outcomes, and quality of life after LVAD in contemporary practice. Methods Adults receiving durable LVADs between January 1, 2010, and March 1, 2020, were identified from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database. The primary outcome was adjusted survival; secondary outcomes included quality of life rated using a visual analogue scale (where 0 represents “worst health” and 100 “best health”); 6-minute walk distance; stroke; device malfunction; and rehospitalization, stratified by patient age. Median follow-up was 15 months (IQR: 6-32 months). Results The cohort comprised 68.9% (n = 16,808) patients aged 75 years, who were predominantly male (n = 19,119, 78%) and on destination therapy (n = 12,425, 51%). Competing outcomes analysis demonstrated mortality (70% CIs) of 34% (33%-34%), 54% (54%-55%), and 66% (64%-68%) for patients aged 75 years, respectively, which improved during the study in patients aged >75 years. Newer-generation devices were associated with reduced late mortality (HR: 0.35; 95% CI: 0.25-0.49). Stroke, device malfunction or thrombosis, and rehospitalizations decreased with increasing age (all P Conclusions In elderly patients, LVADs are associated with increased functional capacity, similar improvements in quality of life, and fewer complications compared with younger patients.

Telesimulation (TS), the process of using the internet to link educators and trainees at locations remote from one another, harnesses the powers of technology to enable access to high-quality simulation-based education and assessment to learners across the globe. From its first uses in the teaching and assessment of laparoscopic skills to more recent interpretations during the current pandemic, TS has shown promise in helping educators to address pressing dilemmas in medical education.

There is tremendous attention in maternal and neonatal disparities, particularly disparities of race and ethnicity and subsequent outcomes that continue despite calls to action. The literature has offered potential opportunities for exploring data related to racial and ethnic disparities, including the utilization of a race and ethnicity reporting dashboard. This article reviews definitions of perinatal quality and disparity and provides insight into the development of a nationally targeted race and ethnicity dashboard. This quarterly dashboard provides hospitals with specific key metric outcomes through the lens of race and ethnicity, provides a national benchmark for comparison, and creates a data platform for team exploration and comprehensive review of findings. An overview of the development of the dashboard is provided, and the selection of key maternal and neonatal metrics is reviewed. In addition, recommendations for data science strategic planning and nursing's role in metric development, analysis, and utilization are offered and key steps in accelerating disparity data into everyday clinical care are discussed.

Background: Despite benefits of breast feeding for both the infants and mothers, its prevalence has remained low worldwide. The present study was conducted to examine the knowledge and attitude towards breast feeding practices among postnatal mothers. Methodology:A cross sectional study was conducted among non-randomly selected postnatal mothers at a tertiary care hospital in North India. Data was collected through a structured online questionnaire administered on electronic tablet before discharge. Results: Among 430 females enrolled in study, majority (98.65%)of the mothers believed breast milk is best nutrition for infant. 211(95%) multipara were breastfeeders, 64 among them had breastfed for more than 2 years. Only 9 mothers had stopped BF before 6 months. However, only 301(78%) had initiated breast feeding within one hour of birth. Early initiation was higher among vaginal (50.34%) compared to Caesarean (25.7%) births. Only 40% mothers observed correct positioning and attachment of infant on breast. Higher number of antenatal visits and correct skill of latching infant on breast were significantly associated with better exclusive BF rates. 91% mothers preferred to increase suckling on breast by infant to tackle problem of inadequate breast milk output. Conclusion: Our findings showed increase knowledge and positive attitude for BF among post natal mothers delivering in hospitals. We emphasise on the importance of prenatal education to mothers and fathers on breast-feeding. We also recommend strengthening the public health education campaigns to promote breast-feeding. Keywords: Attitudes, Breast feeding, India, Infant feeding practices, Knowledge, Mothers.

Changing weather patterns and extreme events are not the only outcomes of global climatic change. We investigate the impact of changing weather conditions on human capital development by studying a...

End-stage renal disease (ESRD) is a condition in which kidney function has permanently declined such that renal replacement therapy* is required to sustain life (1). The mortality rate for patients with ESRD in the United States has been declining since 2001 (2). However, during the COVID-19 pandemic, ESRD patients are at high risk for COVID-19-associated morbidity and mortality, which is due, in part, to weakened immune systems and presence of multiple comorbidities (3-5). The ESRD National Coordinating Center (ESRD NCC) supports the Centers for Medicare & Medicaid Services (CMS) and the ESRD Networks†,§ through analysis of data, dissemination of best practices, and creation of educational materials. ESRD NCC analyzed deaths reported to the Consolidated Renal Operations in a Web-Enabled Network (CROWNWeb), a system that facilitates the collection of data and maintenance of information about ESRD patients on chronic dialysis or receiving a kidney transplant who are treated in Medicare-certified dialysis facilities and kidney transplant centers in the United States. Excess death estimates were obtained by comparing observed and predicted monthly numbers of deaths during February 1-August 31, 2020; predicted deaths were modeled based on data from January 1, 2016, through December 31, 2019. The analysis estimated 8.7-12.9 excess deaths per 1,000 ESRD patients, or a total of 6,953-10,316 excess deaths in a population of 798,611 ESRD patients during February 1-August 31, 2020. These findings suggest that deaths among ESRD patients during the early phase of the pandemic exceeded those that would have been expected based on previous years' data. Geographic and temporal patterns of excess mortality, including those among persons with ESRD, should be considered during planning and implementation of interventions, such as COVID-19 vaccination, infection control guidance, and patient education. These findings underscore the importance of data-driven technical assistance and further analyses of the causes and patterns of excess deaths in ESRD patients.

Purpose To perform a propensity-score matched analysis comparing stereotactic body radiation therapy (SBRT) boost and high-dose-rate (HDR) boost for localized prostate cancer. Methods and Materials A single-institution retrospective chart review was conducted of men treated with pelvic external beam radiation therapy (EBRT) and SBRT boost (21 Gy and 19 Gy in 2 fractions) to the prostate for prostate cancer. A cohort treated at the same institution with HDR brachytherapy boost (19 Gy in 2 fractions) was compared. Propensity-score (PS) matching and multivariable Cox regression were used for analysis. Outcomes were biochemical recurrence freedom (BCRF) and metastasis freedom (MF). Results One hundred thirty-one men were treated with SBRT boost and 101 with HDR boost with median follow-up of 73.4 and 186.0 months, respectively. In addition, 68.8% of men had high-risk and 26.0% had unfavorable-intermediate disease, and 94.3% received androgen deprivation therapy. Five- and 10-year unadjusted BCRF was 88.8% and 85.3% for SBRT and 91.8% and 74.6% for HDR boost (log-rank P = .3), and 5- and 10-year unadjusted MF was 91.7% and 84.3% for SBRT and 95.8% and 82.0% for HDR (log-rank P = .8). After adjusting for covariates, there was no statistically significant difference in BCRF (hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.37-1.79; P = .6) or MF (HR 1.07; 95% CI, 0.44-2.57; P = .9) between SBRT and HDR boost. Similarly, after PS matching, there was no statistically significant difference between SBRT and HDR (BCRF: HR 0.66, 0.27-1.62, P = .4; MF: HR 0.84, 0.31-2.26, P = .7). Grade 3+ genitourinary and gastrointestinal toxicity in the SBRT cohort were 4.6% and 1.5%, and 3.0% and 0.0% in the HDR cohorts (P = .4, Fisher exact test). Conclusions SBRT boost plus pelvic EBRT for prostate cancer resulted in similar BCRF and MF to HDR boost in this single institution, PS matched retrospective analysis. Toxicity was modest. Prospective evaluation of SBRT boost for the treatment of unfavorable-intermediate and high-risk prostate cancer is warranted.

Chronotype reflects circadian timing and can be determined from biological markers (e.g., dim light melatonin onset; DLMO), or questionnaires (e.g., Morningness-Eveningness Questionnaire; MEQ, or Munich Chronotype Questionnaire; MCTQ). The study’s aim was to quantify concordance between chronotype categorisations based on these measures. A total of 72 (36f) young, healthy adults completed the MEQ and MCTQ and provided saliva samples hourly in dim light during the evening in a laboratory. The corrected midpoint of sleep on free days (MSFsc) was derived from MCTQ, and tertile splits were used to define early, intermediate and late DLMO-CT, MEQ-CT and MSFsc-CT chronotype categories. DLMO correlated with MEQ score (r = −0.25, p = 0.035) and MSFsc (r = 0.32, p = 0.015). For early, intermediate and late DLMO-CT categories, mean(SD) DLMO were 20:25(0:46), 21:33(0:10) and 23:03(0:53). For early, intermediate and late MEQ-CT categories, mean(SD) MEQ scores were 60.5(5.3), 51.4(2.9) and 40.8 (5.0). For early, intermediate and late MSFsc-CT categories, mean(SD) MSFsc were 03:23(0:34), 04:37(0:12) and 05:55(0:48). Low concordance of categorisations between DLMO-CT and MEQ-CT (37%), and between DLMO-CT and MSFsc-CT (37%), suggests chronotype categorisations depend on the measure used. To enable valid comparisons with previous results and reduce the likelihood of misleading conclusions, researchers should select measures and statistical techniques appropriate to the construct of interest and research question.

BACKGROUND AND PURPOSE TGFβ1-mediated myofibroblast activation contributes to pathological fibrosis in many diseases including idiopathic pulmonary fibrosis (IPF), where myofibroblast resistance to oxidant-mediated apoptosis is also evident. We therefore investigated the involvement of redox-sensitive TRPA1 ion channels on human lung myofibroblasts (HLMFs) cell death and TGFβ1-mediated pro-fibrotic responses. EXPERIMENTAL APPROACH The effects of TGFβ1 stimulation on TRPA1 expression and cell viability was studied in HLMFs derived from IPF patients and non-fibrotic patients. We also examined a model of TGFβ1-dependent fibrogenesis in human lung. We used qRT-PCR, immunofluorescent assays, overexpression with lentiviral vectors and electrophysiological methods. KEY RESULTS TRPA1 mRNA, protein and ion currents were expressed in HLMFs derived from both non-fibrotic patient controls and IPF patients, and expression was reduced by TGFβ1. TRPA1 mRNA was also down-regulated by TGFβ1 in a model of lung fibrogenesis in human lung. TRPA1 over-expression or activation induced HLMF apoptosis, and activation of TRPA1 channel activation by H2 O2 induced necrosis. TRPA1 inhibition following TGFβ1 down-regulation or pharmacological inhibition, protected HLMFs from both apoptosis and necrosis. Lentiviral vector mediated TRPA1 expression was also found to induce sensitivity to H2 O2 induced cell death in a TRPA1-negative HEK293T cell line. CONCLUSION AND IMPLICATIONS TGFβ1 induces resistance of HLMFs to TRPA1 agonist- and H2 O2 -mediated cell death via down-regulation of TRPA1 channels. Our data suggest that therapeutic strategies which prevent TGFβ1-dependent down-regulation of TRPA1 may reduce myofibroblast survival in IPF and therefore improve clinical outcomes.

Background/objectives: Neuroendocrine neoplasms (NEN) may predispose patients to malnutrition. CT-defined sarcopenia and myosteatosis are common in other tumour types and recognized adverse prognostic factors. However, the prevalence and prognostic impact of sarcopenia and myosteatosis remain undetermined in NEN patients to date. Methods: A retrospective study of NEN patients treated with peptide receptor radionuclide therapy (PRRT) at a tertiary institution from 2012 to 2017. Patients with PET/CT imaging at baseline and follow-up were included. The L3 slice of the co-localizing CT was analysed using the Alberta Protocol. Skeletal muscle cross-sectional area and muscle attenuation were measured and compared with pre-defined cut-offs. The primary endpoint was the prevalence of sarcopenia and myosteatosis according to previously published cut-offs. Results: Fourty-nine patients (median age 64 (range 26–80) years) were included. The most common primary sites of tumour were the small bowel (51%) and pancreas (26%). Baseline sarcopenia was prevalent in 67% of patients and myosteatosis in 71%. Forty-five percent of patients gained weight over the course of PRRT. The presence of baseline sarcopenia was not associated with progression-free survival (20.8 mo vs. 20.7 mo, HR 0.86, p = 0.70) nor overall survival. Similarly, baseline myosteatosis (PFS 19.5 mo vs. 20.8 mo, HR 0.77, p = 0.47) was not significantly associated with survival outcomes. The mean (SD) age of those with myosteatosis was 60.8 ± 11.6 years compared to 49.7 ± 12.7 years for those without (p = 0.003). Conclusions: Body composition analysis is feasible using routinely acquired PET/CT data for patients with NEN. CT-defined sarcopenia and myosteatosis are prevalent in NEN patients, although myosteatosis is more common with increasing age. These findings were not associated with worsened overall or progression-free survival in the current study.

Tumor heterogeneity may impact immunohistochemical (IHC) interpretation, thus potentially affecting decision making by treating oncologists for cancer patient management. Programmed cell death ligand-1 (PD-L1) IHC 22C3 pharmDx is a companion diagnostic used as an aid in identifying patient eligibility for treatment with pembrolizumab (KEYTRUDA). This study aims to investigate tumor heterogeneity impact on IHC staining when evaluating PD-L1 expression using PD-L1 IHC 22C3 pharmDx. The effect of tumor heterogeneity was evaluated based on the PD-L1 diagnostic status of PD-L1 IHC 22C3 pharmDx stained tumor tissue sections at relevant diagnostic cutoffs for non-small cell lung carcinoma, gastric or gastroesophageal junction adenocarcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, esophageal cancer and triple negative breast cancer. Overall agreement for the PD-L1 diagnostic status was assessed for each tumor type within a given specimen block (Intra-Block), between specimen blocks from the same surgical resection (Intra-Case), and between intrapatient primary and metastatic specimens. Intrablock and intracase point estimates were above 75%, and primary versus metastatic point estimates were above 50%. The results suggest that PD-L1 expression is consistent across cut sections through a minimum of 150 µm within a tissue block and between blocks from the same surgical resection and is significantly maintained across primary and metastatic blocks from the same patient despite changes to the tissue microenvironment. These data provide confidence for histopathologists and oncologists that evaluation of PD-L1 expression at clinically relevant cutoffs is reproducible among different assessments (or samplings) of a single tumor specimen.

The recent coronavirus disease of 2019 pandemic has resulted in unprecedented limitations in person-to-person contact, elective surgeries, and even traumatic injuries, leaving potential gaps in training and skill development. Surgical programs have had to adapt with the rapid implementation of surgical simulation curricula, collaborative lecture series, and greater focus on online learning. Using models, simulation, and virtual learning, we have accommodated for restrictions and operative volume from coronavirus disease of 2019. The goal was to establish a durable system of extra-clinical training that would increase patient safety and collaborative knowledge sharing. From our simulated interventions, we noted maintenance of skills despite low operative volumes, low temporal or monetary commitment especially when compared with operating room time, and engagement from both learners (medical students and junior residents) and teachers (senior residents and staff physicians). Our experience with transition to a virtual curriculum with involvement of multiple institutions has also resulted in greater diversity of lectures, increased frequency of academics, and high levels of participation. In this article, we discuss our department's experience with these alterations and the path for surgical training moving forward. We have seen multiple benefits to advancement of nonclinical specialty-specific simulation and virtual didactics. While some of these efforts may require some early expenditure, both monetary and temporal, to establish the program infrastructure, they are easy to apply, confer substantial added value, and appear durable. © 2021 Lippincott Williams and Wilkins. All rights reserved.

Background Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics. Methods The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups. Results Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group. Conclusions Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.

Injuries to the anterolateral ligament (ALL) of the knee are commonly associated with anterior cruciate ligament (ACL) ruptures. Biomechanical studies have demonstrated conflicting results with regard to the role of the ALL in limiting tibial internal rotation. Clinically, residual pivot shift following ACL reconstruction has been reported to occur up to 25% and has been correlated with poor outcomes. As such, surgical techniques have been developed to enhance rotational stability. Recent biomechanical studies have demonstrated restoration of internal rotational control following ALL reconstruction. The purpose of our study was to understand the biomechanical effects of ACL reconstruction with an ALL internal brace augmentation. We hypothesized that (1) sectioning of the ALL while preserving other lateral extra-articular structures would lead to significant internal rotation laxity and gap formation and (2) ALL repair with internal brace augmentation would lead to reduction in internal rotation instability and gap formation. In total, 10 fresh-frozen cadaveric knees were thawed and biomechanically tested in internal rotation for 10 cycles of normal physiologic torque in the intact, ACL-deficient, ACL/ALL-deficient, ACL-reconstructed, and ALL-repaired conditions. Each condition was tested at 30, 60, and 90 degrees of flexion. Following the final ALL-repaired condition, specimens were additionally subjected to a final internal rotation to failure at 1 degree at the last-tested degree of flexion. Kinematic measurements of angle and linear gap between the femur and tibia were calculated in addition to torsional stiffness and failure torque. As hypothesized, ALL repair with internal brace augmentation significantly reduced internal rotation angular motion and gap formation at flexion angles greater than 30 degrees. Additionally, ALL sectioning produced nonsignificant increases in internal rotation laxity and gap formation compared with ACL-deficient and ACL-reconstructed states, which did not support our other hypothesis.

Background:The public health measure restrictions across the world due to COVID-19 have inadvertently impacted the routines for people with Parkinson’s disease (PD) and their care partners not only in terms of compromised neurological clinical care but also drastically changing the way of life to minimize the risk of becoming infected. This study explores initial PD patients’ lived experiences to observe how quality of life and health care has been affected at the start of the COVID-19 pandemic and provide insight into the importance of patient engagement and virtual care.Methods:Twenty-two virtual, in-depth semi-structured interviews with persons diagnosed with PD who usually attend a Movement Disorders specialty clinic in Calgary, Alberta, were completed between April 28 and May 13, 2020, and the care partners that wished to participate. Interviews were recorded and transcribed, after which transcripts were analyzed and coded into relevant themes using NVivo 12.Results:Impacts from the public health measures and COVID-19 results into three main themes: (1) Impacts of COVID-19 on PD Clinical Care; (2) Activities of Daily Living; (3) Attitudes and Perceptions. Participants reported worsening in motor and nonmotor symptoms and had to accommodate to clinical care via virtual means which were associated with limitations and suggestions for improvement of remote care.Conclusion:This study provides a unique opportunity for researchers to better understand the lived experiences of PD patients in all aspects of their life suggesting that innovative means are needed for facilitating virtual health care medicine and increased social interaction.

To understand if anatomic physeal-sparing ACL reconstruction in the immature host preserves range of motion, permits a return to sports, and avoids limb length discrepancy and accelerated intra-articular degeneration with a cross-sectional radiographic, physical examination and patient-reported outcomes analysis. A cross-sectional recall study included 38 patients aged 7–15 who underwent all-epiphyseal ACL reconstruction with hamstring allograft performed by a single surgeon at a large academic medical center. All-epiphyseal reconstructions were performed using a modified Anderson physeal-sparing technique, with the femoral tunnel placed using an “inside-out” technique. Assessments consisted of a physical exam, long leg cassette radiographs, KT-1000 measurements, subjective patient metrics, and magnetic resonance imaging. Thirty-eight (56.7%) of 66 eligible patients returned for in-person clinical and radiographic exams. Patients were 11.4 ± 1.8 years at the time of surgery. Five patients were females (13.2%). Mean follow-up was 5.5 ± 2.4 years. ACL re-injuries occurred in four patients (10.5%), all of whom underwent revision reconstructions. Thirty-three of the remaining 34 (97.1%) patients returned to sports following their reconstruction, and 24 (70.6%) returned to their baseline level of competition. Mean limb length discrepancy (LLD) was 0.2 ± 1.4 cm. Nine patients had an LLD of > 1 cm (26.5%), which occurred at an equivalent age as those with

PurposeThis study investigates whether subordinates who rate their managers higher on narcissism are also more likely to view their managers as abusive. In particular, the study explores the extent to which managers whom subordinates rate higher on narcissism use certain behaviors (self-promotion and unpredictability) that mediate the relationship between narcissism and perceived abuse.Design/methodology/approachSurvey participants (n = 949) rated their most-destructive manager in terms of self-promotion, unpredictability, narcissism and abusiveness. A bootstrap analysis assessed the positive, mediating effects of leader self-promotion and unpredictability on the narcissism–abuse relationship.FindingsDegree of perceived supervisor narcissism predicted subordinates' perceptions of abusive supervision. However, the supervisor's self-promotion activities and unpredictability fully mediated this relationship.Research limitations/implicationsThis study identifies perceived narcissism as an antecedent of abusive supervision and identifies two mediators relevant to subordinates' perceptions of abuse. Using multiple methods and multiple sources, the authors recommend that scholars identify additional mediators. Further research should consider variables such as gender, organizational culture and occupational status.Practical implicationsFindings highlight how subordinates connect supervisor narcissism to abuse; this allows human resource practitioners to better predict and address subordinates' perceptions of their managers and to design interventions for improving supervisors' behaviors.Originality/valueThis study helps in explaining destructive leadership by empirically examining perceptions of narcissism as a driver of abusive supervision. Also, the study reveals the characteristics of narcissistic managers that impede productive relationships with subordinates.

To appropriately route children with developmental disabilities to appropriate early interventions, those children must first be identified via developmental screening and/or developmental monitoring. Most early identification research emphasizes the relationship between developmental screening and Part C early intervention (EI) receipt for children birth to two. The relationship between developmental monitoring and service receipt is understudied, particularly for 3 to 5-year-old children are routed to Part B (619) early childhood special education services. Thus, this study used data from the National Surveys of Children’s Health (2007, 2012) to investigate the relationship between community-based health care providers (HCP) developmental screening and/or monitoring and the odds of early childhood special education receipt for preschool aged children (3 to 5). Across years, children whose HCP provided both developmental screening and monitoring, or developmental monitoring alone, had substantially greater odds of receiving special education compared to those who did not receive screening or monitoring. Receipt of developmental screening alone was associated with special education receipt in 2012, but not 2007. Developmental monitoring is understudied compared to developmental screening. Data presented here indicate that monitoring is associated with Part B 619 special education receipt and warrants further investigation to better understand how, with developmental screening, developmental monitoring might improve the identification of young children in need of 619 services. In particular, longitudinal analyses capturing data across systems, from screening and monitoring to assessment and service receipt, is needed to understand the effectiveness of monitoring for early identification and appropriate routing of children to relevant care systems.