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Juthaporn Cowan,1,2 Sunita Mulpuru,1,2 Sara J Abdallah,2 Anchal Chopra,3 Andrew Purssell,1 Michaeline McGuinty,1 Gonzalo G Alvarez,1,2 Antonio Giulivi,2,4 Vicente Corrales-Medina,1,2 Derek MacFadden,1,2 Loree Boyle,1 Delvina Hasimja,1 Kednapa Thavorn,2,5,6 Ranjeeta Mallick,2 Shawn D Aaron,1,2 D William Cameron1,2 1Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 2Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 3Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; 4Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada; 5School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada; 6Institute for Clinical Evaluative Sciences, Toronto, Ontario, CanadaCorrespondence: Juthaporn Cowan Email jcowan@toh.caBackground: Observational studies suggest that immunoglobulin treatment may reduce the frequency of acute exacerbations of COPD (AECOPD).Objective: To inform the design of a future randomised control trial (RCT) of intravenous immunoglobulin (IVIG) treatment efficacy for AECOPD prevention.Methods: A pilot RCT was conducted. We recruited patients with COPD hospitalized for AECOPD, or from ambulatory clinics with one severe, or two moderate AECOPD in the previous year regardless of their serum IgG level. Patients were allocated in a 1:1 ratio with balanced randomisation to monthly IVIG or normal saline for 1 year. The primary outcome was feasibility defined as pre-specified accrual, adherence, and follow-up rates. Secondary outcomes included safety, tolerance, AECOPD rates, time to first AECOPD, quality of life, and healthcare costs.Results: Seventy patients were randomized (37 female; mean age 67.7; mean FEV1 35.1%). Recruitment averaged 4.5± 0.9 patients per month (range 0– 8), 34 (49%) adhered to at least 80% of planned treatments, and four (5.7%) were lost to follow-up. There were 35 serious adverse events including seven deaths and one thromboembolism. None was related to IVIG. There were 56 and 48 moderate and severe AECOPD in the IVIG vs control groups. In patients with at least 80% treatment adherence, median time to first moderate or severe AECOPD was 275 vs 114 days, favoring the IVIG group (HR 0.76, 95% CI 0.3– 1.92).Conclusion: The study met feasibility criteria for recruitment and retention, but adherence was low. A trend toward more robust treatment efficacy in adherent patients supports further study, but future trials must address treatment adherence.Trial registration number: NCT0290038, registered 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690038 and NCT03018652, registered January 12, 2017, https://clinicaltrials.gov/ct2/show/NCT03018652.Keywords: recurrent AECOPD, pilot RCT, immunoglobulin treatment, IVIG

Michail Sideris,1,* Marios Nicolaides,2,* Jade Jagiello,3 Kathrine S Rallis,2 Elif Emin,1 Efthymia Theodorou,2 John Gerrard Hanrahan,4 Rebecca Mallick,5 Funlayo Odejinmi,6 Nikolaos Lymperopoulos,7 Apostolos Papalois,8 George Tsoulfas9 1Women’s Health Research Unit, Queen Mary University of London, London, UK; 2Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 3University College London Hospital, London, UK; 4Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, UK; 5Princess Royal Hospital, Brighton and Sussex University Hospitals NHS Trust, Haywards Heath, UK; 6Whipps Cross University Hospital, Barts Health NHS Trust, London, UK; 7Guy’s and St Thomas Hospitals NHS Foundation Trust, London, UK; 8Special Unit for Biomedical Research and Education, Aristotle University of Thessaloniki, Thessaloniki, Greece; 9Department of Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece*These authors contributed equally to this workCorrespondence: Michail SiderisWomen’s Health Research Unit, Queen Mary University of London, Yvonne Carter Building, 58 Turner Street, London, E1 2AB, UKEmail m.sideris@qmul.ac.ukAbstract: An increasing emphasis on simulation has become evident in the last three decades following fundamental shifts in the medical profession. Simulation-based learning (SBL) is a wide term that encompasses several means for imitating a skill, attitude, or procedure to train personnel in a safe and adaptive environment. A classic example has been the use of live animal tissue, named in vivo SBL. We aimed to review all published evidence on in vivo SBL for undergraduate medical students; this includes both teaching concepts as well as focused assessment of students on those concepts. We performed a systematic review of published evidence on MEDLINE. We also incorporated evidence from a series of systematic reviews (eviCORE) focused on undergraduate education which have been outputs from our dedicated research network (eMERG). In vivo SBL has been shown to be valuable at undergraduate level and should be considered as a potential educational tool. Strict adherence to 3R (Reduce, Refine, Replace) principles in order to reduce animal tissue usage, should always be the basis of any curriculum. In vivo SBL could potentially grant an extra mile towards medical students’ inspiration and aspiration to become safe surgeons; however, it should be optimised and supported by a well-designed curriculum which enhances learning via multi-level fidelity SBL.Keywords: in vivo simulation-based learning, medical simulation, surgical education

Purpose: The objective of this study is to determine primary survival endpoints in women with recurrent and metastatic endometrial carcinoma (RMEC) treated with progestins. Methods: A retrospective chart review was conducted at The Ottawa Hospital using electronic medical records. Inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥one line of progestin treatment. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Of 2342 cases reviewed, 74 met inclusion criteria. Sixty‐six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of tumors by grade was: 1: 25 (33.3%), 2: 30 (40.0%), and 3: 20 (26.7%). The PFS and OS for the entire study sample was 14.3 months (95% CI 6.2–17.9) and 23.3 months (14.8–36.8), respectively. The PFS for patients with Grade 1–2 RMEC was 15.7 months (8.0, 19.5), compared to 5.0 months (3.0, 23.0) with Grade 3 disease. The OS for patients with Grade 1–2 versus Grade 3, was 25.9 months (15.3, 40.3) versus 12.5 months (5.7, 35.9), respectively. Thirty‐four (45.9%) and 40 (54.1%) patients were treated with 0 and ≥1 line of chemotherapy. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. Conclusions: This real‐world data on RMEC suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. This real‐world data on recurrent and metastatic endometrial carcinoma (RMEC) suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following>=1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. [ABSTRACT FROM AUTHOR]

Prajna Jena1, Soumitra Mohanty1, Rojee Mallick1, Biju Jacob2, Avinash Sonawane11School of Biotechnology, KIIT University, Bhubaneswar, Orissa, India; 2Center for Innovation, Technopark Technology Business Incubator, Bangalore, Karnataka, IndiaBackground: Pathogenic bacteria are able to develop various strategies to counteract the bactericidal action of antibiotics. Silver nanoparticles (AgNPs) have emerged as a potential alternative to conventional antibiotics because of their potent antimicrobial properties. The purpose of this study was to synthesize chitosan-stabilized AgNPs (CS-AgNPs) and test for their cytotoxic, genotoxic, macrophage cell uptake, antibacterial, and antibiofilm activities.Methods: AgNPs were synthesized using chitosan as both a stabilizing and a reducing agent. Antibacterial activity was determined by colony-forming unit assay and scanning electron microscopy. Genotoxic and cytotoxic activity were determined by DNA fragmentation, comet, and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Cellular uptake and intracellular antibacterial activity were tested on macrophages.Results: CS-AgNPs exhibited potent antibacterial activity against different human pathogens and also impeded bacterial biofilm formation. Scanning electron microscopy analysis indicated that CS-AgNPs kill bacteria by disrupting the cell membrane. CS-AgNPs showed no significant cytotoxic or DNA damage effect on macrophages at the bactericidal dose. Propidium iodide staining indicated active endocytosis of CS-AgNPs resulting in reduced intracellular bacterial survival in macrophages.Conclusion: The present study concludes that at a specific dose, chitosan-based AgNPs kill bacteria without harming the host cells, thus representing a potential template for the design of antibacterial agents to decrease bacterial colonization and to overcome the problem of drug resistance.Keywords: chitosan-silver nanoparticles, antibiofilm, cytotoxicity, genotoxicity

Biopriming and integrated disease management have the potential to reduce the hazards associated with the increasing use of agrochemicals in agriculture. Field trials were therefore conducted during the two consecutive summer seasons of 2020 and 2021 at Agricultural Experimental Farm, Institute of Agricultural Science, University of Calcutta, West Bengal to evaluate the impact of biopriming and integrated disease management (IDM) practices on disease incidence in sesame as well as its productivity. The treatments consisted of three modules, viz., Bio-intensive (M1): Seed treatment with Trichoderma asperellum @10 g kg-1 + furrow application of enriched Trichoderma (2.5 kg Trichoderma asperellum + 100 kg vermicompost) @250 kg ha-1 + spray of Pseudomonas fluorescens @10 g L-1 at 30-35 DAS and wettable sulphur @2 g L-1 at 50-60 DAS; Chemical (M2): Seed treatment with carbendazim @2 g L-1 + spray of combi-product (Tebuconazole 50% + Trifloxystrobin 25%) @0.5 g L-1 at 30-35 DAS and second spray @2 g L-1 at 50-60 DAS; Adaptive (M3): Seed treatment with Trichoderma asperellum @10 g kg-1 + furrow application of enriched Trichoderma (2.5 kg Trichoderma asperellum + 100 kg vermicompost) @250 kg ha-1+ spray of combi-product (Tebuconazole 50% + Trifloxysrobin 25%) @0.5 g L-1 at 30-35 DAS and second spray at 50-60 DAS, and Control (M4): Untreated check. The results revealed that the adaptive module, M3, was highly effective and recorded significantly the lowest disease incidence of root rot (18.9%), severity of Alternaria (11.0%) and Cercospora leaf spots (7.0%) with highest seed yield of 0.59 t ha-1 and highest benefit:cost ratio of 2.13:1. This module can be used for the effective management of root rot and leaf spot diseases of sesame and ensuring sustained yields, particularly in the coastal agro-climatic condition of West Bengal. [ABSTRACT FROM AUTHOR]

Background: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada. Methods: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut. Results: A total of 247 people were offered 3HP, 102 in the Iqaluit postmarketing study and 145 in the Qikiqtarjuaq program roll out. Although statistical significance was not reached, more people who started treatment completed treatment in the 3HP group (Iqaluit, 60/73 (82.2%) and Qikiqtarjuaq, 89/115 (77.4%)) than in the historical control 9INHgroup (306/420 = 72.9%) (p = 0.2). Most of the adverse events in 3HP treated patients were associated with mild discomfort but no disruption of normal daily activity. Not drinking alcohol was associated with increased 3HP completion (OR 13.33, 95% CI, 2.27–78.20) as was not taking concomitant medications (OR 7.19, 95% CI, 1.47–35.30). Conclusions: The present study supports the feasibility and safety profile of 3HP for the treatment of LTBI in Nunavut. [ABSTRACT FROM AUTHOR]

Introduction Cyclophosphamide-bortezomib-dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib-dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony-stimulating factor (gcsf). Plerixa for was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106 cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide-gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship. [ABSTRACT FROM AUTHOR]

Background and purpose: Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long‐term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient‐reported outcomes in patients on SCIG are assessed. Methods: Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5‐Dimension (EQ‐5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work‐related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI‐GH). The EQ‐5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ‐5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI‐GH were assessed by median score changes from baseline to week 25. Results: In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20‐treated subjects improved/maintained their health status on the EQ‐5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI‐GH scores were more stable with IgPro20 treatment compared with placebo. Conclusions: IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP. [ABSTRACT FROM AUTHOR]

REFERENCES 1 Zbiri S, Fauconnier A, Milcent C. Care for uterine fibroids: another casualty of the COVID pandemic. We read with interest the recently published article by Saad Zbiri[1] and colleagues "Care for uterine fibroids: another casualty of the COVID pandemic', addressing the poor care of women with fibroids during the COVID-19 pandemic. Finally, access to emergency care may only be the tip of the iceberg with regard to the negative impact on women with fibroids during the pandemic. [Extracted from the article]

Effects of steady-state rifabutin on the pharmacokinetics of steady-state maraviroc were investigated in fourteen healthy adult female and male volunteers. Maraviroc 300 mg twice daily (BID) was given orally with food for fifteen days. On day six, rifabutin 300 mg once daily (QD, P.O.) was added to the regimen. Formal pharmacokinetic (PK) sampling was performed on days five and fifteen. Individual plasma drug concentration-time data for maraviroc, and rifabutin on day fifteen, were obtained using validated High Performance Liquid Chromatography (HPLC) tandem Mass Spectrometry (MS/MS). Rifabutin steady state exposure was comparable to data in the literature. Maraviroc area under the curve (AUC) and minimum plasma concentration (Clast or Cmin) were reduced by 17% and 30% respectively when co-administered with rifabutin. No unexpected or serious adverse eventsoccurred. Based on the reduced exposure of maraviroc observed in this study, increasing the dose of maraviroc may be studied to normalize its moderately reduced exposure following rifabutin co-administration, a moderate inducer of CYP3A4. [ABSTRACT FROM AUTHOR]

Background Diagnosis and treatment of renal cell carcinoma (rcc) might be different in Indigenous Canadians than in non-Indigenous Canadians. In this cohort study, we compared rcc presentation and treatments in Indigenous and non-Indigenous Canadians. Methods Patients registered in the Canadian Kidney Cancer Information System treated at 16 institutions between 2011 and 2018 were included. Baseline patient, tumour, and treatment characteristics were compared between Indigenous and non-Indigenous Canadians. The primary objective was to determine if differences in rcc stage at diagnosis were evident between the groups. The secondary objective was to determine if treatments and outcomes were different between the groups. Results During the study period, 105 of the 4529 registered patients self-identified as Indigenous. Those patients were significantly younger at the time of clinical diagnosis (57.9 ± 11.3 years vs. 62.0 ± 12.1 years, p = 0.0006) and had a family history prevalence of rcc that was double the prevalence in the non-Indigenous patients (14% vs. 7%, p = 0.004). Clinical stage at diagnosis was similar in the two groups (p = 0.61). The disease was metastatic at presentation in 11 Indigenous Canadians (10%) and in 355 non-Indigenous Canadians (8%). Comorbid conditions that could affect the management of rcc--such as obesity, renal disease, diabetes mellitus, and smoking--were more common in Indigenous Canadians (p < 0.05). Indigenous Canadians experienced a lower rate of active surveillance (p = 0.01). Treatments and median time to treatments were similar in the two groups. Conclusions Compared with their non-Indigenous counterparts, Indigenous Canadian patients with rcc are diagnosed at an earlier age and at a similar clinical stage. Despite higher baseline comorbid conditions, clinical outcomes are not worse for Indigenous Canadians than for non-Indigenous Canadians. [ABSTRACT FROM AUTHOR]

Background: The goal of radical prostatectomy is to achieve the optimal balance between complete cancer removal and preserving a patient's urinary and sexual function. Performing a wider excision of peri-prostatic tissue helps achieve negative surgical margins, but can compromise urinary and sexual function. Alternatively, sparing peri-prostatic tissue to maintain functional outcomes may result in an increased risk of cancer recurrence. The objective of this study is to determine the effect of providing surgeons with detailed information about their patient outcomes through a surgical report card.Methods: We propose a prospective cohort quasi-experimental study. The intervention is the provision of feedback to prostate cancer surgeons via surgical report cards. These report cards will be distributed every 3 months by email and will present surgeons with detailed information, including urinary function, erectile function, and surgical margin outcomes of their patients compared to patients treated by other de-identified surgeons in the study. For the first 12 months of the study, pre-operative, 6-month, and 12-month patient data will be collected but there will be no report cards distributed to surgeons. This will form the pre-feedback cohort. After the pre-feedback cohort has completed accrual, surgeons will receive quarterly report cards. Patients treated after the provision of report cards will comprise the post-feedback cohort. The primary comparison will be post-operative function of the pre-feedback cohort vs. post-feedback cohort. The secondary comparison will be the proportion of patients with positive surgical margins in the two cohorts. Outcomes will be stratified or case-mix adjusted, as appropriate. Assuming a baseline potency of 20% and a baseline continence of 70%, 292 patients will be required for 80% power at an alpha of 5% to detect a 10% improvement in functional outcomes. Assuming 30% of patients may be lost to follow-up, a minimum sample size of 210 patients is required in the pre-feedback cohort and 210 patients in the post-feedback cohort.Discussion: The findings from this study will have an immediate impact on surgeon self-evaluation and we hypothesize surgical report cards will result in improved overall outcomes of men treated with radical prostatectomy. [ABSTRACT FROM AUTHOR]

A field experiment was conducted during rabi (winter) seasons of 2007-08 and 2008-09 to study the effect of integrated nutrient management on growth, yield, oil content and nutrient uptake of yellow sarson (Brassica campestris L var. yellow sarson) in older alluvial soil of West Bengal. Significantly higher leaf area index (1.75 at 40 days after sowing; DAS), dry matter accumulation (1366.9 g/m2 at 80 DAS) and highest number of siliquae/plant (118.3), number of seeds/siliqua (21.8), seed yield (1.90 t/ha), stover yield (3.86 t/ha) were recorded significantly (at 5% level) higher with poultry manure (PM) @2.5t/ha +50%RDF (Recommended Dose of Fertilizer i.e. 80-40-40 of N-P2O5-K2O kg/ha) + PSB (phosphate solubilising bacteria) + AZ (Azotobacter) during both the years and on pooled basis. An average of 30.5% and 233% increase in seed yield by this treatment was recorded over sole application of RDF and control respectively. Integrated application of PM (2.5 t/ha) + 50% RDF + PSB + AZ recorded highest oil content (43.16%) and positive effect on soil fertility status. The highest benefit: cost ratios (2.26 and 2.4 in 2007-'08 and 2008-'09 respectively) were achieved from the use of 50% RDF + PM (2.5 t/ha) +PSB+AZ. [ABSTRACT FROM AUTHOR]

A field experiment was conducted during rabi season of 2007-'08 and 2008-'09 to study the effect of calcium nitrate {Ca (NO3)2} and potassium nitrate {KNO3} at 50 % flowering stage and soil applied nitrogen {N: (0, 40 and 80 kg N/ha)} on growth, productivity and economics of yellow sarson at farmers field under irrigated old alluvial soil of West Bengal. Highest leaf area index (LAI) values at 40 days of crop age (1.748 and 1.592), dry matter accumulation (1404.3 and 1288.8 gm-2) at 80 days and crop growth rate (C.G.R) (27.87 and 25.68 g m-2 day-1) in between 40 to 60 days were obtained at Nitrogen application at the rate of 80 kg / ha and mixed spray of 0.203 % Ca (NO3)2 + 0.25 % KNO3 respectively. Soil application of 80 kg N/ ha along with foliar spray of 0.203 % Ca (NO3)2 + 0.25 % KNO3 resulted increase in seed yield (1.68 t ha-1) by 12 % over 80 kg N/ ha with only water spray (1.5 t ha-1). Foliar spray of 0.203 % Ca (NO3)2 + 0.25 % KNO3 improved the yield components and seed yield over their sole application. Application of 80 kg N/ha along with 0.203 % Ca (NO3)2 + 0.25 % KNO3 at 50 % flowering stage was found to be the most effective in increasing yellow sarson production in old alluvial soil. [ABSTRACT FROM AUTHOR]

To determine whether the introduction of a physician remuneration incentive within certain Canadian provinces resulted in increased practice of laparoscopic hysterectomy over time. Retrospective population-based study with interrupted time series analysis of federal health administrative data from the Canadian Institute for Health Information Hospitals in all the provinces of Canada, excluding territories 81,507 patients aged ≥18 years undergoing hysterectomy for benign gynecologic indication in Canada from 2006/07 to 2016/17 Hysterectomy Reviewof physician remuneration fee schedules for each province in Canada identified three provinces where a physician incentive (additional 25-50% remuneration) was introduced: British Columbia (BC) (2013), Saskatchewan (SK) (2012), and Prince Edward Island (PEI) (2011). During the 10-year period, the rates of laparoscopic hysterectomy increased rapidly in BC (6.0%-54.7%), SK (13.5%-66.7%), and PEI (<1.0%-36.9%) (p <0.05 for all trends). In SK (n=7,857 hysterectomies), there was a significant additional increase in the rate of laparoscopic hysterectomy from 40.6% to 49.4% in the quarter following the incentive (p <0.0001). In BC (n=16,332), there was no significant additional increase in the rate of laparoscopic surgeries after the introduction of a financial incentive. Though PEI appeared to demonstrate an increase in the rate of laparoscopic hysterectomy following the incentive, ITS analyses were not performed due to the small sample size (n=2,583). The introduction of physician remuneration incentive appears to be associated with an increase in practice of laparoscopic hysterectomy in some provinces but not others. While physician incentive may help encourage minimally invasive surgical practice, the effects are likely modified by other important factors, such as operating room resources and training opportunities. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This retrospective study used the US Oncology iKnowMed™ database, billing claims, and chart reviews to report treatment patterns and outcomes in late-stage non-small cell lung cancer (NSCLC) in US community oncology practices. Materials and methods: Eligibility criteria included non-squamous NSCLC, stage IIIB/IV at diagnosis, ECOG performance status (PS) <3, and initiation of 2nd-line therapy (defined as index date) between 1/1/2007 and 6/30/2011 with ≥1 year follow-up. Key outcomes were overall survival (OS), progression-free survival (PFS), time-to-progression (TTP), and time-to-hospitalization (post-index date). Kaplan–Meier and Cox proportional hazard models were used to characterize the distribution and predictors of outcomes. Results: 1168 patients were eligible for the study. The most frequent 2nd-line therapies were pemetrexed (54.4%), erlotinib-containing regimens (17.6%), and docetaxel (10.0%). Median OS and PFS were 7.5 (95% confidence interval [CI]: 6.6–8.4) and 4.1 (95% CI: 3.7–4.5) months, respectively; 57% of patients were hospitalized post-index date. EGFR testing rates were 2.3% before 2010, 15.2% in 2010, and 32.0% in 2011 (P <.001). Of EGFR-positive patients, 50.0% received erlotinib-containing regimens compared with 16.9% of EGFR-negative patients (P =0.001). An increased risk of shorter time-to-hospitalization, after controlling for other covariates, was associated with PS=1 (hazard ratio [HR]=1.51; P <.001) or PS=2 (HR=1.68; P =.001) compared with PS=0, pre-existing comorbid fatigue (HR=1.64; P =.003) compared with no comorbid fatigue, and progression (HR=1.92; P <.001), when it occurred, compared with no progression. Compared with other 2nd-line treatment, erlotinib-containing regimens prolonged adjusted TTP (HR=0.69; P =.015). Conclusions: This retrospective observational study provides new insights into treatment patterns, biomarker testing, and outcomes in advanced NSCLC within the context of a large community oncology network. Outcomes of these community practice patients, although poor, were similar to those reported in 2nd-line clinical trials for relevant regimens. EGFR testing in community practice rose rapidly after 2010. [Copyright &y& Elsevier]

Background: The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone.Methods: We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patient's forced expiratory volume in 1 s (FEV(1)) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life.Results: At 14 days the mean±SE change in FEV(1) from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI -10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08).Conclusions: Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%.Clinical Trials: gov number NCT 00789997. [ABSTRACT FROM AUTHOR]

In this paper, a robust non-linear controller for a two-area voltage source converter high voltage DC (VSC-HVDC) transmission system is proposed subject to model uncertainties and external disturbances. The non-linear controller uses a robust feedback linearisation control for the voltage source pulse-width modulation (PWM) converter and inverter system of the DC-link along with a linear H∞ control strategy. The purpose of the converter control is to ensure independent control of the active and reactive power flow in the system while maintaining a constant DC voltage at the same time. For achieving robust feedback linearisation unlike the classical one requires the control of the square of the DC voltage rather than the DC voltage itself. This control strategy may provide the insight for the design of input-output linearised system, in which zero dynamics contain some desirable state variables. The controlled PWM has the global stability, fast tracking of DC bus voltage with zero steady-state error, rejection of exogenous disturbances, and stabilisation of synchronous generators connected to the VSC-HVDC systems at the two ends. [ABSTRACT FROM AUTHOR]

The agronomic performance of 18 M4 generation mutants of aromatic rice (Oryza sativa L.) was evaluated along with their two mother genotypes, IET 14142 and IET 14143. IET 1412 and IET14143 were developed from Tulaipanja, an aromatic non-basmati rice cultivar, popularly grown in northern parts of West Bengal - an important rice growing province of India. The results indicate that there is a considerable amount of genetic variability among mutants with respect to thirteen quantitative characters. Some of the mutants had a combination of both positive and negative forms of important yield contributing characters. The performance of four mutants (T1m1, T1m6, T2m4 and T2m8) indicated considerable improvement in grain yield over their respective control. The increased grain yield per plant in the above high yielding mutants is primarily due to increase in panicle number per plant, spikelet number per panicle, grain number per panicle and test weight. These mutants need further evaluation in multilocation trials to judge their potential as varieties of aromatic rice. The other mutants may be used in cross-breeding programmes of aromatic rice for agronomically useful characters i.e., early flowering, short stature, erect flag leaf, high grain number, heavy weight per 100 grains. The apparent changes in different characters in an individual mutant may not be due to genetic changes in all the affected characters. The possible role of pleiotropic effects of mutant genes cannot be ruled out. [ABSTRACT FROM AUTHOR]

The potential of harvesting heat energy from asphalt pavement using a piping network with fluid flowing through it needs to be evaluated before spending a significant amount of time on planning details of design and construction. The key factors involved in this evaluation include the temperature of the pavement at the depth at which the system is being considered, as well as the temperature of the fluid used for harvesting the heat energy. Costs include those required for the system such as pumps and pipes, and cost of energy required for pumping. Taking all of the factors into consideration, a macro-enabled spreadsheet has been developed that allows the user to input air temperature data as well as pipe location and cost parameters. The end results are data on flow rate versus yearly savings and payback period. From these data, a user can easily determine whether the payback period is reasonable or not and could also evaluate the effect of the different parameters on the payback period. Examples of the results of analysis for different cities in four different parts of the USA and Singapore and Chennai, India, are presented. The payback period shows a good relationship with the latitude of the location - the period increases with an increase in latitude. The public domain location from where the spreadsheet can be downloaded is provided. [ABSTRACT FROM AUTHOR]

In this paper a voltage source converter based high voltage direct current (VSCHVDC) transmission link is considered for the development of a multivariable robust controller to stabilize the AC-VSC-HVDC power system. To maintain the dc voltage and control the active and reactive power at the converter and inverter stations simultaneously a robust H∞control design methodology is adopted here. For designing the controller output feedback quantities like the converter side dc voltage and reactive power and the inverter side active and reactive power are obtained and used to satisfy an and H∞norm of the closed loop transfer function matrix. The proposed controller is evaluated for different power system operating conditions like the threephase short-circuits on the converter and inverter buses, short-circuit on the dc line, loading changes, etc. and its performance show better results than the earlier used PI controllers in respect of the reduction of overshoots, faster settling times, and improved damping for the electromechanical oscillations of the generators. [ABSTRACT FROM AUTHOR]

Intrusion of water through longitudinal joints can cause premature distress in hot mix asphalt (HMA) pavements. Similar to mat permeability, joint permeability is a critical factor governing the performance of HMA pavements. Hence, joint permeability should be used as a measure of quality of joint construction. In this ongoing study, a simple and effective permeameter has been developed, and used in a rational method to evaluate the permeability of longitudinal joints, relative to the permeability of the adjacent mat. The permeameter consists of three standpipes, which can be used for measuring the flow of water through a joint and through the mat on either side of the joint. Results from testing on several projects show that this permeameter can be used successfully to determine permeability of joints. The testing performed in this study shows that joints have significantly higher permeability compared to adjacent mats, different types of joints have different permeabilities and that treatment of joints with sealers and using improved joint construction techniques such as joint heater can reduce the permeability significantly. More testing of joints is being carried out, with the objective of developing specific criteria for using the joint permeameter for quality control of construction of longitudinal joints. [ABSTRACT FROM AUTHOR]

It is now possible to search for new drugs using high-throughput screening of chemical libraries accumulated over the past few years. To detect potential new hyperthermia sensitizers, we are screening for chemical inhibitors of thermotolerance. For the screening of a large chemical library, a rapid and simple assay based on the XTT-tetrazolium salt with the addition of intermediate electron acceptor, phenazine methosulphate (PMS) as a promoter, was developed. It was found that the sensitivity of the XTT/PMS assay is sufficient for assessing thermal cell killing and thermotolerance, although it was highly dependent on cell number and type. When the formazan assay system was challenged with the bioflavonoid drug quercetin (up to 25mm) and validated against the clonogenic cell survival assay, significant decreases in thermotolerant cell viability were observed, directly reflecting inhibition of thermotolerance. Although short-term assays can, in some instances, underestimate overall cell killing, the dose dependency of inhibition of thermotolerance by quercetin recorded in this study by clonogenic and XTT/PMS assays was similar. Application of the XTT/PMS assay in chemical library screening was highly effective in differentiating potential thermotolerance inhibitors from both chemicals with lack of efficacy and from toxic compounds. Taken together, these results show that the XTT/PMS assay, when carried out under careful conditions, is well suited for primary high-flux screen of many thousands of compounds, thus opening up new areas for discovery of hyperthermia sensitizers. [ABSTRACT FROM AUTHOR]

It has previously been demonstrated that hyperthermia can activate prostaglandin synthesis and that prostaglandins are protective against hyperthermia. This study examined the use of inhibitors of prostaglandin synthesis on the response of prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit prostaglandin production, were effective hyperthermia sensitizers and augmented growth delay of DU-145 and PC-3 prostate tumours to combined radiation and hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01) inhibition of hyperthemia-induced serum prostaglandin E[sub 2]. These findings indicate that NSAID may have both sensitizing effects on prostate tumour growth and may function by inhibiting prostaglandin synthesis. [ABSTRACT FROM AUTHOR]

This study used published relative risk estimates for birth defects, premature birth, and coronary heart disease associated with vitamin intake to project potential annual cost reductions in U.S. hospitalization charges. Epidemiological and intervention studies with relative risk estimates were identified via MEDLINE. Preventable fraction estimates were derived from data on the percentage of at-risk Americans with daily vitamin intake levels lower than those associated with disease risk reduction. Hospitalization rates were obtained from the 1992 National Hospital Discharge Survey. Charge data from the 1993 California Hospital Discharge Survey were adjusted to 1995 national charges using the medical component of the Consumer Price Index. Based on published risk reductions, annual hospital charges for birth defects, low-birth-weight premature births, and coronary heart disease could be reduced by about 40, 60, and 38%, respectively. For the conditions studied, nearly $20 billion in hospital charges were potentially avoidable with daily use of folic acid and zinc-containing multivitamins by all women of childbearing age and daily vitamin E supplementation by those over 50. [ABSTRACT FROM AUTHOR]

A versatile system has been designed and fabricated to prepare atom-probe field-ion-microscope (APFIM) specimens in a systematic manner, such that internal interfaces can be positioned in the tips of these wire specimens for subsequent analysis of their chemical composition. This system incorporates both beaker electrolytic and zone electrolytic cell configurations, a specially constructed power supply, and a special transmission electron microscope holder for wires. The power supply enables ac electroetching or dc electropolishing in the automated or manual modes. The ac wave forms available are sine (0.002 Hz–200 kHz) or square (10 Hz–20 kHz). Triggering and gating are performed manually or with a pulse generator. The dc output is gated manually to produce a continuous output or with a pulse generator to produce single pulses with widths in the range 50 μs–1 s. A counter indicates the number of periods of voltage applied, and the total charge transferred in the electrolytic cell is integrated in the range 10 μA s–1 kA s. The power supply provides 0 to ±48 V peak at 1 A peak. A double-tilt stage for an Hitachi H-700H 200 kV transmission electron microscope (TEM) was radically modified to hold APFIM specimens; this stage is vibrationless at 310 000× magnification. It has a tilting range of ±30° and ±27° for the x and y tilts, respectively. Examples are given of the controlled backpolishing of W-3 at. % Re, W-25 at. % Re, Mo-5.4 at. % Re, and Fe-3 at. % Si specimens, and their observation by TEM, to selectively place grain boundaries in the tip region. The analysis of the chemical composition of a grain boundary, which is first located in a W-25 at. % Re specimen via TEM, by the APFIM technique is presented. [ABSTRACT FROM AUTHOR]