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We want to understand to what extend product market fit concepts can be applied to deep tech startups considering the challenges and specificities of those compared to "shallow" or "traditional" startups. At the end, it should provide (1) a comprehensive definition of product market fit and (2) first insights on how product market fit concepts could be applied to deep tech startups.

We want to collect insights into effective monitoring and response to challenges brought by cybercrime in law enforcement. Data will be collected via mixed methods, constituting of interviews and a survey.

I want to derive the impact of a digital project on efficiency and costs through interviews with intralogistics experts.

I want to derive the impact of a digital strategy on efficiency and costs through interviews.

Objective: COVID-19 can cause acute respiratory distress syndrome (ARDS) that is rapidly progressive, severe, and refractory to conventional therapies. Extracorporeal membrane oxygenation (ECMO) can be used as a supportive therapy to improve outcomes but evidence-based guidelines have not been defined. Summary Background Data: Initial mortality rates associated with ECMO for ARDS in COVID-19 were high, leading some to believe that there was no role for ECMO in this viral illness. With more experience, outcomes have improved. The ideal candidate, timing of cannulation, and best post-cannulation management strategy, however, has not yet been defined. Methods: We conducted a retrospective review from April 1 to July 31 2020 of the first 25 patients with COVID-19 associated ARDS placed on V-V ECMO at our institution. We analyzed the differences between survivors to hospital discharge and those who died. Modified Poisson regression was used to model adjusted risk factors for mortality. Results: 44% of patients (11/25) survived to hospital discharge. Survivors were significantly younger (40.5 years vs. 53.1 years; p < 0.001) with no differences between cohorts in mean body mass index, diabetes, or PaO2:FiO2 at cannulation. Survivors had shorter duration from symptom onset to cannulation (12.5 days vs. 19.9 days, p = 0.028) and shorter duration of intensive care unit (ICU) length of stay (LOS) prior to cannulation (5.6 days vs. 11.7 days, p = 0.045). Each day from ICU admission to cannulation increased the adjusted risk of death by 4% and each year increase in age increased the adjusted risk 6%. Conclusions: ECMO has a role in severe, refractory ARDS associated with COVID-19. Increasing age and time from ICU admission were risk factors for mortality and should be considered in patient selection. Further studies are needed to define best practices for V-V ECMO use in COVID-19.

AIM To evaluate the normal numerical and graphic values of nocturnal penile tumescence (NPT) test using Androscan MIT in healthy males in order to use the collected data as reference standard. MATERIALS AND METHODS NPT monitoring was carried out in 38 healthy male volunteers by fixing a sensor designed for 20 measurements on their penis. During the NPT test the following parameters were recorded: 1) total sleep time; 2) minimal penis diameter (PD) in the flaccid state recorded by the apparatus; 3) maximum PD during effective penile tumescence; 4) absolute PD increase during effective erections; 5) increase in PD in %; 6) the overall time of the rigid-erection phase; 7) the number of penile rigidity episodes; 8) the average duration of each effective erection; 9) the percentage of rigid erections during the whole monitoring period. RESULTS Based on the data collected by Androscan MIT, we have specified the numerical values which characterize normal physiological NPT indices in healthy male volunteers. The number of tests performed and similar inclusion criteria contribute to the objectiveness of the presented data. Normal sleep time was from 7.3 to 9.5 hours. Monitoring during sleeping reflected the upper and lower limits of the minimal PD value recorded by Androscan MIT, which was from 23.5 mm to 30.2 mm. The maximum PD increase during the most effective erection varied from 35.3 mm to 44.3 mm. Total PD increase was from 10.6 mm to 15.4 mm (from 35.6% to 59.2%). In all cases a significant difference in PD increase between flaccid state and effective erection during sleeping was seen. The number of penile rigidity episodes varied from 3 to 7 a night. The overall time of effective erections was from 62.3 to 206.7 minutes, while the minimum duration of a single erection episode was 16.4 minutes and the maximum duration reached 35.8 minutes. The ratio of effective NPT to the total sleep time (the percentage of penile rigidity episodes) varied from 11.9% to 41.3%. CONCLUSION Our results allowed to define reference qualitative and quantitative values of NPT in healthy male volunteers recorded by Androscan MIT which can be considered as normal and physiological and used for differential diagnostics of erectile dysfunction.

Background The spleen is the most commonly injured organ in blunt abdominal trauma. The management for splenic trauma includes nonoperative management, splenectomy, and splenic artery angioembolization. The aim of this study is to investigate recent trends in the usage of splenic artery angioembolization in patients with isolated blunt splenic trauma. Methods Adult patients (age >15) with isolated blunt splenic trauma were identified from the National Trauma Databank (2007–2015) using International Classification of Diseases, Ninth Revision, codes. The defined groups included nonoperative management, splenectomy, and splenic artery angioembolization. Patient variables collected included year of traumatic injury, age, sex, race, insurance status, and geographic region. Clinical variables collected included vital signs (systolic blood pressure, pulse, respiratory rate) recorded upon arrival to the emergency room, injury severity score, abbreviated injury severity scores, diagnoses, procedures, and mechanism. Outcome measures included mortality, hospital duration of stay, and complications. We performed 2 independent Poisson logistic regression models to assess relative risk for both splenectomy and angioembolization. Results A total of 10,812 patients were included in the analysis (nonoperative management: 7,920; splenectomy: 2,083; angioembolization: 809). Angioembolization proportion increased from 2007 (4.6%) to 2015 (10%), while splenectomy proportion remained unchanged (19.2% to 18.3%). Poisson logistic regression suggests the adjusted probability of receiving angioembolization for a splenic injury increased year-to-year, while the adjusted probability of receiving a splenectomy remained unchanged. Conclusion The use of angioembolization for isolated blunt splenic injuries has increased over the past decade without a reciprocal change in splenectomy. Based on this study, angioembolization may be an overused resource without a significant benefit.

Background:Although rare, coronary artery anomalies can have significant clinical implications. Total anomalous origin of the coronary arteries from the pulmonary artery (TCAPA) represents a rare subtype of coronary artery anomaly for which little is known. The aim of this review was to characterise the presentation, utilised diagnostic modalities, associated cardiac lesions, and treatment strategies in patients with TCAPA.Methods:A systematic review was performed for cases of TCAPA using PubMed, Embase, and Web of Science. Keywords searched included “total anomalous origin of the coronary arteries from the pulmonary artery,” “single ostium anomalous coronary artery from the pulmonary artery,” and “anomalous origin of both coronary arteries from the pulmonary artery.”Results:Fifty-seven cases of TCAPA were identified in 50 manuscripts. Fifty-eight per cent of patients were male and the median age at presentation was 10 days (mean 1.71 ± 6.6 years, range 0 days–39 years). Most patients were symptomatic at the time of presentation; cyanosis (n = 22) and respiratory distress (n = 14) were the most common symptoms. Cases were most commonly diagnosed at autopsy (n = 26, 45.6%), but operative intervention was pursued in 22 cases (45.6%); aortic re-implantation (n = 14) and a Takeuchi-type repair (n = 7) were the most common routes of repair.Conclusions:The clinical presentation of patients with TCAPA was found to be variable, likely related to the presence of associated cardiac lesions. TCAPA should be considered in patients with suspected anomalous origin of the left coronary artery from the pulmonary artery for the serious consequences that can occur if not promptly corrected.

Summary Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants. During the meeting, concise summaries of the recorded lectures were presented, followed by small group breakout discussions. Consensus opinions from each group were collated into a draft document, which was reviewed and approved by all participants. Recommendations regarding use of laboratory tests, imaging, and treatment options are presented, along with algorithms for diagnosis of Cushing's syndrome and management of Cushing's disease. Topics considered most important to address in future research are also identified.

Aims Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS). Methods and results Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age ( Conclusion Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification.

OBJECTIVES This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) according to sex.BACKGROUND Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFRCT improves sex-based patient management decisions compared to CCTA alone is unknown.METHODS Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFRCT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFRCT management plans, incidence of ICA demonstrating obstructive CAD ($50% stenosis) and revascularization rates.RESULTS A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFRCT. Women were older (age 68 +/- 10 years vs. 65 +/- 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFRCT (0.76 +/- 0.10 vs. 0.73 +/- 0.10; p < 0.0001), and lower likelihood of positive FFRCT

Q fever is a worldwide zoonosis caused by Coxiella burnetii that can lead to abortion, endocarditis, and death in humans. Researchers utilizing parturient domestic ruminants, including sheep, have an increased risk of occupational exposure. This study evaluated the effectiveness of our screening protocol in eliminating C. burnetii–positive sheep from our facility. From August 2010 to May 2018, all ewes ( N = 306) and select lambs ( N = 272; ovis aries) were screened twice for C. burnetii utilizing a serum Phase I and Phase II antibody immunofluorescence assay (IFA). The first screen was performed by the vendor prior to breeding, and the second screen was performed on arrival to the research facility. Ewes that were positive on arrival screening were quarantined and retested using repeat IFA serology, enzyme-linked immunosorbent assay, buffy coat polymerase chain reaction (PCR), and amniotic fluid PCR. The overall individual seroprevalence of C. burnetii in the flocks tested by the vendor was 14.2%. Ewes with negative Phase I and Phase II IFA results were selected for transport to the research facility. Upon arrival to the facility, two (0.7%) ewes had positive Phase I IFA results. Repeat testing demonstrated seropositivity in one of these two ewes, though amniotic fluid PCR was negative in both. The repeat seropositive ewe was euthanized prior to use in a research protocol. No Q fever was reported among husbandry, laboratory or veterinary staff during the study period. Serologic testing for C. burnetii with IFA prior to transport and following arrival to a research facility limits potential exposure to research staff.

Exercise after breast cancer diagnosis and treatment improves cancer-related outcomes, although the mechanisms involved are not clear. This study evaluated the impact of exercise on body composition, strength, endurance, quality of life (QOL), fatigue, and endocrine and inflammatory biomarkers in breast cancer survivors participating in a highly monitored, clinically supervised, moderate-intensity exercise program. The association of hormonal and inflammatory biomarkers with the observed physiological changes was assessed. Female breast cancer survivors (BCS; n = 46) who engaged in a goal-oriented 14-week triathlon exercise training program were compared to an untrained control group of female BCS (n = 16). Psychosocial metrics, QOL, cancer-related fatigue, and exercise self-efficacy were evaluated via pre- and post-exercise intervention questionnaires. Serum estradiol and inflammatory biomarkers (C-reactive protein (CRP), sTNFR1a, estradiol, leptin, and adiponectin) were measured prior to the exercise training program start and after the completion of the goal triathlon. After exercise training, the exercise group had lower BMI and arm circumferences. Greater positive change was noted in the trained group for QOL, fatigue, and self-efficacy questionnaires. Functional endurance improved in the trained but not the control group. Knee and elbow strength were not different between the groups, except that knee flexion at 180 degrees∙sec−1 was higher in trained. The only significantly different biomarker was adiponectin, which decreased in the trained group. Group triathlon exercise training may be beneficial to BCS by significantly improving their psychosocial measures, functional endurance, and BMI.

The risk and progression of pulmonary vascular disease in patients with congenital heart disease is dependent on the hemodynamics associated with different lesions. However, the underlying mechanisms are not understood. Endothelin-1 is a potent vasoconstrictor that plays a key role in the pathology of pulmonary vascular disease. We utilized two ovine models of congenital heart disease: (1) fetal aortopulmonary graft placement (shunt), resulting in increased flow and pressure; and (2) fetal ligation of the left pulmonary artery resulting in increased flow and normal pressure to the right lung, to investigate the hypothesis that high pressure and flow, but not flow alone, upregulates endothelin-1 signaling. Lung tissue and pulmonary arterial endothelial cells were harvested from control, shunt, and the right lung of left pulmonary artery lambs at 3–7 weeks of age. We found that lung preproendothelin-1 mRNA and protein expression were increased in shunt lambs compared to controls. Preproendothelin-1 mRNA expression was modestly increased, and protein was unchanged in left pulmonary artery lambs. These changes resulted in increased lung endothelin-1 levels in shunt lambs, while left pulmonary artery levels were similar to controls. Pulmonary arterial endothelial cells exposed to increased shear stress decreased endothelin-1 levels by five-fold, while cyclic stretch increased levels by 1.5-fold. These data suggest that pressure or an additive effect of pressure and flow, rather than increased flow alone, is the principal driver of increased endothelin signaling in congenital heart disease. Defining the molecular drivers of the pathobiology of pulmonary vascular disease due to differing mechanical forces will allow for a more targeted therapeutic approach.

PURPOSE To identify which internal medicine clerkship characteristics may relate to NBME Medicine Subject Examination scores, given the growing trend toward earlier clerkship start dates. METHOD The authors used linear mixed effects models (univariable and multivariable) to determine associations between medicine exam performance and clerkship characteristics (longitudinal status, clerkship length, academic start month, ambulatory clinical experience, presence of a study day, involvement in a combined clerkship, preclinical curriculum type, medicine exam timing). Additional covariates included number of NBME clinical subject exams used, number of didactic hours, use of a criterion score for passing the medicine exam, whether medicine exam performance was used to designate clerkship honors, and United States Medical Licensing Examination Step 1 performance. The sample included 24,542 examinees from 62 medical schools spanning 3 academic years (2011-2014). RESULTS The multivariable analysis found no significant association between clerkship length and medicine exam performance (all pairwise P > .05). However, a small number of examinees beginning their academic term in January scored marginally lower than those starting in July (P < .001). Conversely, examinees scored higher on the medicine exam later in the academic year (all pairwise P < .001). Examinees from schools that used a criterion score for passing the medicine exam also scored higher than those at schools that did not (P < .05). Step 1 performance remained positively associated with medicine exam performance even after controlling for all other variables in the model (P < .001). CONCLUSIONS In this sample, the authors found no association between many clerkship variables and medicine exam performance. Instead, Step 1 performance was the most powerful predictor of medicine exam performance. These findings suggest that medicine exam performance reflects the overall medical knowledge students accrue during their education rather than any specific internal medicine clerkship characteristics.

PURPOSE: To determine whether gestational carrier (GC) in vitro fertilization (IVF) cycles (commissioned cycles) for same-sex or single male intended parents have an increased incidence of adverse perinatal outcomes compared with spontaneous cycles in the same GCs. DESIGN: GC singleton pregnancies were identified from a database of 895 commissioned cycles from a large fertility center. Of these, 78 commissioned cycles met inclusion and exclusion criteria and were compared with 71 spontaneous cycles by the same GCs. The primary outcome was the composite score for adverse perinatal outcomes. Secondary outcomes included mode of delivery, birthweight, and gestational age. Chi-square test of association and Mann-Whitney U tests were used to compare categorical and continuous variables between the cohorts, respectively. Logistic and linear regressions controlling for GC age were constructed to determine the influence of GC cycle type on adverse perinatal outcomes. RESULTS: Commissioned cycles were significantly associated with adverse perinatal outcomes (25.6% vs. 9.9%; p = 0.02) and lower average gestational age (38.7 ± 1.5 vs. 39.4 ± 0.9; p

This case-control cohort study analyzes patients with suspected coronary atherosclerosis and control patients to identify the factors associated with higher or lower risks for adverse cardiovascular events and acute coronary syndrome.Key PointsQuestionIs the density of coronary calcified plaque associated with future development of acute coronary syndrome? FindingsIn this case-control study of 189 patients who experienced vs 189 control individuals who did not experience an acute coronary syndrome after baseline coronary computed tomography angiography imaging, the volume of plaque with more than 1000 Hounsfield unit (termed 1K plaque) was associated with lower risk for acute coronary syndrome. The specific acute coronary syndrome precursor culprit lesion had less 1K plaque compared with the most stenotic lesion in control individuals. MeaningThis study's findings suggest that 1K plaque detected by coronary computed tomography angiography is associated with lower risk of future occurrence of acute coronary syndrome.ImportancePlaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. ObjectiveTo ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and ParticipantsThis multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n=189) and control individuals who did not experience ACS after baseline CCTA (n=189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. ExposuresWhole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and MeasuresAssociation between calcium density and future ACS risk. ResultsA total of 189 patients and 189 matched controls (mean [SD] age of 59.9[9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm(3) vs 99.0 [156.1] mm(3); P=.32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm(3) vs 9.4 [23.2] mm(3); P=.02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P

Objectives The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFRCT) with downstream care and clinical outcomes. Background Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. Methods Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFRCT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. Results At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFRCT ≤0.80 and in 89 (5.60%) with an FFRCT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p 0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFRCT ≤0.80 compared with 10 (0.60%) patients with an FFRCT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFRCT ≤0.80 compared with patients with an FFRCT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). Conclusions The 1-year outcomes from the ADVANCE FFRCT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFRCT compared with patients with abnormal FFRCT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679)

Our multi-institutional university consortium implemented a gastroschisis pathway in 2015 to standardize and improve care by promoting avoidance of routine intubation and paralysis during silo placement, expeditious abdominal wall closure, discontinuation of antibiotics/narcotics within 48 h of closure, and early initiation/advancement of feeds.Adherence to the gastroschisis pathway was prospectively monitored. Outcomes for the contemporary cohort (2015-2018) were compared with a historical cohort (2007-2012).Good adherence to the pathway was observed for 70 cases of inborn uncomplicated gastroschisis. The contemporary cohort had significantly lower median mechanical ventilator days (2 versus 5; p 0.01) and antibiotic days (5.5 versus 9; p 0.01) as well as earlier days to initiation of feeds (12 versus 15; p 0.01). However, no differences were observed in length of stay (28 versus 29 days; p = 0.70). A skin closure technique was performed in 66% of the patients, of which 46% were performed at bedside without intubation, the assistance of an operating-room team, or general anesthesia.In this study, adherence to a clinical pathway for gastroschisis across different facilities was feasible and led to reduction in exposure to mechanical ventilation and antibiotics. The adoption of a bedside skin closure technique appears to facilitate compliance with the pathway.Level II/III TYPE OF STUDY: Prospective comparative study with historical cohort.

Aims The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea. Methods and results From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for ≥5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 ± 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1–6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29–1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02–1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD. Conclusion In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk.

BACKGROUND: ECMO is an established supportive adjunct for patients with severe, refractory ARDS from viral pneumonia. However, the exact role and timing of ECMO for COVID-19 patients remains unclear. METHODS: We conducted a retrospective comparison of the first 32 patients with COVID-19-associated ARDS to the last 28 patients with influenza-associated ARDS placed on V-V ECMO. We compared patient factors between the two cohorts and used survival analysis to compare the hazard of mortality over sixty days post-cannulation. RESULTS: COVID-19 patients were older (mean 47.8 vs. 41.2 years, p = 0.033), had more ventilator days before cannulation (mean 4.5 vs. 1.5 days, p

We study whether and how politicians can influence the behaviour of CEOs and firm performance with prestigious government awards. We present a simple model to develop the hypothesis that government awards have a negative effect on firm performance. The empirical analysis uses two legal reforms in New Zealand for identification: knighthoods and damehoods were abolished in April 2000 and reinstated in March 2009. The findings are consistent with the predictions of the model. The results suggest that government awards serve as an incentive tool through which politicians influence firms in favour of employees to the detriment of shareholders.

Background Cellulitis has many potential mimickers, and its misdiagnosis often leads to unnecessary hospitalizations and higher health care costs. The ALT-70 predictive model offers an objective tool to help differentiate between cellulitis and other clinically similar conditions at the time of initial emergency department (ED) presentation. Objective To evaluate the performance of the ALT-70 predictive model at 24 and 48 hours following ED presentation. Methods We performed a retrospective review of our prior cohort and expanded our data collection to include data at 24 and 48 hours after initial ED presentation. We compared classification measures for the ALT-70 at the time of initial ED presentation, 24 hours after presentation, and 48 hours after presentation. Results There was a statistically significant difference in median ALT-70 score between patients with true cellulitis and those with mimickers of cellulitis at all time points. Sensitivity, specificity, positive predictive value, and negative predictive value of the ALT-70 score was similar across all 3 time points. Limitations Single-center design may reduce generalizability. Conclusion At 24 and 48 hours, the ALT-70 performed similarly to the way it performed at the time of initial ED presentation, allowing for its use in a wider array of clinical settings.

While a "fourth peak" of delayed trauma mortality has been described, limited data describe the causes of death (CODs) for patients in the years following an injury. This study investigates the difference in COD statewide for patients with and without a recent trauma admission.This retrospective cohort study compared COD for trauma and nontrauma patients in North Carolina. Death certificates in NC's death registry were matched with the NC trauma registry between January 2013 and December 2018 using matching on name and date of birth. Patients who died during the index trauma admission were excluded. Underlying COD recorded on the death certificate were used for the primary analysis.Of 481,415 death records, 19,083 (4.0%) were linked to an alive discharge within the trauma registry during the study period. Prior trauma patients (PTPs) had a higher incidence of mental illness (9.2 vs. 6.1%), Alzheimer's (6.1% vs. 4.2%), and opioid-related (1.8% vs. 1.6%) COD compared to nontrauma patients, p0.05. Overall, suicide was higher in the nontrauma cohort (1.5% vs. 1.1%); however, PTP had higher incidences of death by motor vehicle collision and other injury (6.0% vs. 3.8%) and homicide (0.9% vs. 0.6%), p0.001. Prior trauma patients had 1.16 increased odds of an opioid-related death (p = 0.009; 95% confidence interval, 1.04-1.29) compared with those without prior trauma. Younger PTP had a much higher rate of death from suicide (12.0%) compared with those 41 to 65 years (2.8%) and older than 65 years (0.2%; p0.001). Discharge to skilled nursing facility (odds ratio, 1.87; p0.05) and severe injury (odds ratio, 1.93; p0.05) were associated with early death after discharge (≤90 days).After hospital discharge, PTPs remain at risk of dying from future trauma and opioid-related conditions. Prevention strategies for PTP should address the increased risk of death from a subsequent traumatic injury and the at-risk populations for early death after discharge.Prognostic and Epidemiologic, Level IV.

Due to a serious pandemic scenario, the surface disinfection process using monochromatic light sources based on UV-C LEDs is becoming more and more required. A brief review of the optoelectronics parameters of the devices based on UV-C LEDs light sources and the UV-C dose required to achieve a 99,9% of inactivation on surfaces (3 log reduction) of human Coronavirus (HCov-OC43 used as SARS-CoV-2 surrogate) has been prepared. A new parameter labeled as “homogeneity factor” has been defined to be applied on a bounded area where the homogeneity of the distribution requires a reliable average dose.

Hypoxia, a common stressor with preterm birth, increases morbidity and mortality associated with prematurity. Glucocorticoids (GCs) are administered to the preterm infant to improve oxygenation; prolonged use of GCs remains controversial. We evaluated a selective glucocorticoid receptor (GR) antagonist (CORT113176) in our neonatal rat model of human prematurity to assess how fasting and hypoxia-induced increases in neonatal corticosterone affects endogenous hormones and endocrine pancreas function. Neonatal rat pups at postnatal day (PD) 2, PD8, and PD15 were pretreated with CORT113176 and, after 60 minutes of separation and fasting, exposed to hypoxia (8% O2) or control (normoxia) for 30 or 60 minutes while fasting was continued. Plasma corticosterone, ACTH, glucose, and insulin were measured and fasting Homeostatic Model Assessment of Insulin Resistance was calculated. Glucocorticoid and insulin receptor-sensitive gene mRNAs were analyzed in liver, muscle, and adipose to evaluate target tissue biomarkers. CORT113176 pretreatment augmented baseline and hypoxia-induced increases in corticosterone and attenuated hypoxia-induced increases in insulin resistance at PD2. Normoxic and hypoxic stress increased the hepatic GR-sensitive gene mRNAs, Gilz and Per1; this was eliminated by pretreatment with CORT113176. CORT113176 pretreatment decreased baseline insulin receptor-sensitive gene mRNAs Akt2, Irs1, Pik3r1, and Srebp1c at PD2. We show that CORT113176 variably augments the stress-induced increases in corticosterone concentrations (attenuation of negative feedback) and that GR is critical for hepatic responses to stress in the hypoxic neonate. We also propose that measurement of Gilz and Per1 mRNA expression may be useful to evaluate the effectiveness of GR antagonism.

In some problem spaces, the high cost of obtaining ground truth labels necessitates use of lower quality reference datasets. It is difficult to benchmark model performance using these datasets, as evaluation results may be biased. We propose a supplement to using reference labels, which we call an approximate ground truth refinement (AGTR). Using an AGTR, we prove that bounds on specific metrics used to evaluate clustering algorithms and multi-class classifiers can be computed without reference labels. We also introduce a procedure that uses an AGTR to identify inaccurate evaluation results produced from datasets of dubious quality. Creating an AGTR requires domain knowledge, and malware family classification is a task with robust domain knowledge approaches that support the construction of an AGTR. We demonstrate our AGTR evaluation framework by applying it to a popular malware labeling tool to diagnose over-fitting in prior testing and evaluate changes whose impact could not be meaningfully quantified under previous data., to appear in Proceedings of the 14th ACM Workshop on Artificial Intelligence and Security

Purpose Hemiparesis and physical deconditioning following stroke lead to an increase in falls, which many individuals cannot get up from. Teaching stroke survivors to independently get off the floor (IGO) might mitigate long-lie complications. IGO was taught as part of a community-based, functional rehabilitation training programme (ReTrain). We explore the feasibility of teaching IGO and assess participant's level of mastery, adherence, and injury risk. Materials and methods Videos of participants (n = 17) performing IGO at early, middle, and late stages of the ReTrain programme were compared to a manualised standard. A visual, qualitative analysis was used to assess technique mastery, adherence, and injury risk. Results Most participants (64%) achieved independent, safe practice of IGO. A good (73%) level of adherence to IGO and low incidence of risk of injury (6.8%) were observed. Deviations were made to accommodate for non-stroke related comorbidities. Conclusions IGO was successfully and safely practised by stroke survivors including those with hemiparesis. Trainers should be aware of comorbidities that may impede completion of IGO and modify teaching to accommodate individual need. Further research should assess if IGO can be utilised by individuals who have other disabilities with unilateral impairments and whether IGO has physical, functional and economic benefit.Implications for rehabilitationFalls are common in stroke survivors, and many are unable to get up despite being uninjured, leading to long-lie complications or ambulance call-outs but non-conveyance to hospital.Teaching the independently getting up off the floor (IGO) technique to stroke survivors was possible for those with or without hemiparesis, and remained safe despite modifications to accommodate an individual's needs.Individual assessment is needed to check if a stroke survivor is suitable for learning IGO including, but not limited to, their ability to safely get to the floor and to temporarily stand (without support) at the end of the technique.

BACKGROUND A paucity of evidence exists regarding risks and benefits of extracorporeal membrane oxygenation (ECMO) in adult liver transplantation. METHODS This was a systematic review conducted from January 1, 2000 to April 24, 2020 of adult liver transplant recipients (pre- or post-transplant) and donors who underwent Veno-arterial or Veno-venous ECMO cannulation. Death was the primary outcome, with graft function and complications as secondary outcomes. RESULTS Forty-one articles were identified that fit criteria. A total of 183 donors were placed on ECMO, with recipient complication profiles and mortality that mirrored rates from standard criteria donors. Sixty-one recipients were placed on ECMO intraoperatively or postoperatively. Most patients experienced at least one complication with infections as the most common cause and minimal complications specifically related to ECMO use. Multisystem organ failure (MSOF) and infections were more common among liver recipients who died compared to those who survived. Overall mortality at 90 days was 45.9%. Causes of death were most commonly MSOF and infections. CONCLUSIONS ECMO use in adult liver transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO parallel that of recipients from standard criteria donors, and morbidity and mortality of recipients placed on ECMO are similar to other ECMO populations.

Thermal images reveal medically important physiological information about human stress, signs of inflammation, and emotional mood that cannot be seen on visible images. Providing a method to generate thermal faces from visible images would be highly valuable for the telemedicine community in order to show this medical information. To the best of our knowledge, there are limited works on visible-to-thermal (VT) face translation, and many current works go the opposite direction to generate visible faces from thermal surveillance images (TV) for law enforcement applications. As a result, we introduce favtGAN, a VT GAN which uses the pix2pix image translation model with an auxiliary sensor label prediction network for generating thermal faces from visible images. Since most TV methods are trained on only one data source drawn from one thermal sensor, we combine datasets from faces and cityscapes. These combined data are captured from similar sensors in order to bootstrap the training and transfer learning task, especially valuable because visible-thermal face datasets are limited. Experiments on these combined datasets show that favtGAN demonstrates an increase in SSIM and PSNR scores of generated thermal faces, compared to training on a single face dataset alone.

Cellulitis is frequently misdiagnosed owing to its clinical mimickers, collectively known as pseudocellulitis. This study investigated diffuse reflectance spectroscopy (DRS) alone and in combination with infrared thermography (IRT) for the differentiation of cellulitis from pseudocellulitis. A prospective cohort study at an urban academic hospital was conducted from March 2017 to March 2018. Patients presenting to the emergency department with presumed cellulitis were screened for eligibility, and 30 adult patients were enrolled. Dermatology consultation conferred a final diagnosis of cellulitis or pseudocellulitis. DRS measurements yielded a spectral ratio between 556 nm (deoxyhemoglobin peak) and 542 nm (oxyhemoglobin peak), and IRT measurements yielded temperature differentials between the affected and unaffected skin. Of the 30 enrolled patients, 30% were diagnosed with pseudocellulitis. DRS revealed higher spectral ratios in patients with cellulitis (P = 0.005). A single parameter model using logistic regression on DRS measurements alone demonstrated a classification accuracy of 77.0%. A dual parameter model using linear discriminant analysis on DRS and IRT measurements combined demonstrated a 95.2% sensitivity, 77.8% specificity, and 90.0% accuracy for cellulitis prediction. DRS and IRT combined diagnoses cellulitis with an accuracy of 90%. DRS and IRT are inexpensive and noninvasive, and their use may reduce cellulitis misdiagnosis.

Background Coronary artery fractional flow reserve (FFR) derived from CT angiography (FFTCT) enables functional assessment of coronary stenosis. Prior clinical trials showed 13%-33% of coronary CT angiography studies had insufficient quality for quantitative analysis with FFRCT. Purpose To determine the rejection rate of FFRCT analysis and to determine factors associated with technically unsuccessful calculation of FFRCT. Materials and Methods Prospectively acquired coronary CT angiography scans submitted as part of the Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care (ADVANCE) registry (https://ClinicalTrials.gov: NCT02499679) and coronary CT angiography series submitted for clinical analysis were included. The primary outcome was the FFRCT rejection rate (defined as an inability to perform quantitative analysis with FFRCT). Factors that were associated with FFRCT rejection rate were assessed with multiple linear regression. Results In the ADVANCE registry, FFRCT rejection rate due to inadequate image quality was 2.9% (80 of 2778 patients; 95% confidence interval [CI]: 2.1%, 3.2%). In the 10 621 consecutive patients who underwent clinical analysis, the FFRCT rejection rate was 8.4% (n = 892; 95% CI: 6.2%, 7.2%; P < .001 vs the ADVANCE cohort). The main reason for the inability to perform FFRCT analysis was the presence of motion artifacts (63 of 80 [78%] and 729 of 892 [64%] in the ADVANCE and clinical cohorts, respectively). At multivariable analysis, section thickness in the ADVANCE (odds ratio [OR], 1.04; 95% CI: 1.001, 1.09; P = .045) and clinical (OR, 1.03; 95% CI: 1.02, 1.04; P < .001) cohorts and heart rate in the ADVANCE (OR, 1.05; 95% CI: 1.02, 1.08; P < .001) and clinical (OR, 1.06; 95% CI: 1.05, 1.07; P < .001) cohorts were independent predictors of rejection. Conclusion The rates for technically unsuccessful CT-derived fractional flow reserve in the ADVANCE registry and in a large clinical cohort were 2.9% and 8.4%, respectively. Thinner CT section thickness and lower patient heart rate may increase rates of completion of CT fractional flow reserve analysis. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sakuma in this issue.

Artificial intelligence (AI)-based decision-making systems are employed nowadays in an ever growing number of online as well as offline services-some of great importance. Depending on sophisticated learning algorithms and available data, these systems are increasingly becoming automated and data-driven. However, these systems can impact individuals and communities with ethical or legal consequences. Numerous approaches have therefore been proposed to develop decision-making systems that are discrimination-conscious by-design. However, these methods assume the underlying data distribution is stationary without drift, which is counterfactual in many realworld applications. In addition, their focus has been largely on minimizing discrimination while maximizing prediction performance without necessary flexibility in customizing the tradeoff according to different applications. To this end, we propose a learning algorithm for fair classification that also adapts to evolving data streams and further allows for a flexible control on the degree of accuracy and fairness. The positive results on a set of discriminated and non-stationary data streams demonstrate the effectiveness and flexibility of this approach.

Grapheme-to-phoneme conversion is an important component in many speech technologies, but until recently there were no multilingual benchmarks for this task. The second iteration of the SIGMORPHON shared task on multilingual grapheme-to-phoneme conversion features many improvements from the previous year’s task (Gorman et al. 2020), including additional languages, a stronger baseline, three subtasks varying the amount of available resources, extensive quality assurance procedures, and automated error analyses. Four teams submitted a total of thirteen systems, at best achieving relative reductions of word error rate of 11% in the high-resource subtask and 4% in the low-resource subtask.

Disinfection of surfaces by ultraviolet-C (UV-C) radiation is gaining importance in diverse applications. However, there is generally no accepted computational procedure to determine the minimum irradiation times and UV-C doses required for reliable and secure disinfection of surfaces. UV-C dose distributions must be comparable for devices presently on the market and future ones, as well as for the diverse surfaces of objects to be disinfected. A mathematical model is presented to estimate irradiance distributions. To this end, the relevant parameters are defined. These parameters are the optical properties of the UV-C light sources, such as wavelength and emitted optical power, as well as electrical features, like radiant efficiency and consumed power. Furthermore, the characteristics and geometry of the irradiated surfaces as well as the positions of the irradiated surfaces in relation to the UV-C light sources are considered. Because mercury (Hg) lamps are competitive with UV-C light-emitting diodes, a comparative analysis between these two light sources based on the simulation results is also discussed.

The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technology. Measurements were performed in samples collected during the acute VTE event and at 12-month follow-up. An 11-protein signature (CLEC4C, FABP4, FLT3LG, IL-17C, LEP, LYVE1, MASP1, ST2, THBS2, THBS4, TSLP) for body mass in VTE patients was identified. The signature did not significantly mediate the obesity paradox (change in hazard ratio [HR]: 0.04; likelihood ratio test of nested models = 7.7; P = .74), but its main constituent protein, leptin, was inversely associated with recurrent VTE or death (adjusted HR [95% confidence interval] per standard deviation increase: 0.66 [0.46-0.94]). This relationship was significantly (P = .007) modified by markers of leptin resistance (ie, high body mass index and high circulating matrix metalloproteinase-2 levels). Although the signature did not substantially explain the obesity paradox, leptin appears to be protective against disease recurrence and death in VTE patients. This protective effect was abrogated under conditions of leptin resistance and hence was unrelated to the obesity paradox.

OBJECTIVES This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).BACKGROUND Coronary CTA can noninvasively assess coronary plaques quantitatively.METHODS Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.RESULTS Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a dosed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm(3) [interquartile range (IQR): 0.0 to 39.6 mm(3)]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm(3) [IQR: 0.0 to 127.4 mm(3)]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm(3) [IQR: 96.7 to 306.4 mm(3)]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p< 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p= 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.CONCLUSIONS The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque Determined by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411) (C) 2021 by the American College of Cardiology Foundation.

We describe an asymptomatic 7-year-old boy who was taken to the operating room for repair of a subaortic membrane and possible Gerbode's defect. He was found to have a double outlet right atrium associated with an accessory atrioventricular valve in addition to a small atrial septal defect and subaortic membrane. Regurgitant flow through this accessory valve led to the left ventricle to right atrial shunt that was seen on preoperative ECHO. The atrial septal defect was repaired and a baffle was used to isolate blood flow across the accessory valve from the left atrium to the left ventricle. The patient was discharged on postoperative day 4 and has been doing well 2 years postoperatively.

Design Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and its prevalence is constantly rising worldwide. Diagnosis is commonly in the late second or early third trimester of pregnancy, though the development of GDM starts early; hence, first-trimester diagnosis is feasible. Objective Our objective was to identify microRNAs that best distinguish GDM samples from those of healthy pregnant women and to evaluate the predictive value of microRNAs for GDM detection in the first trimester. Methods We investigated the abundance of circulating microRNAs in the plasma of pregnant women in their first trimester. Two populations were included in the study to enable population-specific as well as cross-population inspection of expression profiles. Each microRNA was tested for differential expression in GDM vs control samples, and their efficiency for GDM detection was evaluated using machine-learning models. Results Two upregulated microRNAs (miR-223 and miR-23a) were identified in GDM vs the control set, and validated on a new cohort of women. Using both microRNAs in a logistic-regression model, we achieved an AUC value of 0.91. We further demonstrated the overall predictive value of microRNAs using several types of multivariable machine-learning models that included the entire set of expressed microRNAs. All models achieved high accuracy when applied on the dataset (mean AUC = 0.77). The significance of the classification results was established via permutation tests. Conclusions Our findings suggest that circulating microRNAs are potential biomarkers for GDM in the first trimester. This warrants further examination and lays the foundation for producing a novel early non-invasive diagnostic tool for GDM.

The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends risk enhancers in the borderline-risk and statin recommended/intermediate-risk groups. We determined the risk reclassification by the presence and severity of coronary computed tomography angiography (CCTA)-visualized coronary artery disease (CAD) according to statin eligibility groups. Of 35,281 individuals who underwent CCTA, 1,303 asymptomatic patients (age 59, 65% male) were identified. Patients were categorized as low risk, borderline risk, statin recommended/intermediate risk or statin recommended/high risk according to the guideline. CCTA-visualized CAD was categorized as no CAD, nonobstructive, or obstructive. Major adverse cardiovascular events (MACE) were defined as a composite outcome of all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization (>90 days). We tested a reclassification wherein no CAD reclassifies downward, and the presence of any CAD reclassifies upward. During a median follow-up of 2.9 years, 93 MACE events (7.1%) were observed. Among the borderline-risk and statin-recommended/intermediate-risk groups eligible for risk enhancers, the presence or absence of any CCTA-visualized CAD led to a net increase of 2.3% of cases and 22.4% of controls correctly classified (net reclassification index [NRI] 0.27, 95% CI 0.13 to 0.41, p = 0.0002). The NRI was not significant among low- or statin-recommended/high-risk patients (all p > 0.05). The presence or absence of CCTA-visualized CAD, including both obstructive and nonobstructive CAD, significantly improves reclassification in patients eligible for risk enhancers in 2018 ACC/AHA guidelines. Patients in low- and high-risk groups derive no significant improvement in risk reclassification from CCTA. (C) 2019 Published by Elsevier Inc.

A crisis is occurring in that reproductive endocrinologists are not doing the surgeries that are a part of their discipline. We list those procedures as a blueprint for training reproductive endocrinologists.

Background - Unanticipated responses by research participants can influence randomised controlled trials (RCTs) in multiple ways, many of which are poorly understood. This study used qualitative interviews as part of an embedded process evaluation to explore the impact participants may have on the study, but also unintended impacts the study may have on them.Aim - The aim of the study was to explore participants’ experiences and the impact of trial involvement in a pilot RCT in order to inform the designing and delivery of a definitive RCT.Methods - In-depth interviews with 20 participants (10 in the intervention and 10 in the control group) enrolled in a stroke rehabilitation pilot trial. A modified framework approach was used to analyse transcripts.Results - Participation in the study was motivated partly by a desperation to receive further rehabilitation after discharge. Responses to allocation to the control group included an increased commitment to self-treatment, and negative psychological consequences were also described. Accounts of participants in both control and intervention groups challenge the presumption that they were neutral, or in equipoise, regarding group allocation prior to consenting to randomisation.Conclusions - Considering and exploring participant and participation effects, particularly in the control group, highlights numerous issues in the interpretation of trial studies, as well as the in ethics of RCTs more generally. While suggestions for a definitive trial design are given, further research is required to investigate the significant implications these findings may have for trial design, monitoring and funding.Trial registration - ClinicalTrials.gov, NCT02429180. Registered on 29 April/2015.

This study explores the effects of environmental enforcement on the amount of environmental labor employed by facilities regulated under the U.S. Clean Water Act. The study uses panel data from a unique survey of chemical manufacturing facilities operating between 1999 and 2001. Specifically, the analysis examines the influence of monitoring inspections and enforcement actions, e.g., fines, on the number of employees allocated to environmental management. Empirical results show that environmental enforcement negatively affects the amount of environmental labor allocated by the sampled facilities. Specifically, increases in federal inspections, informal enforcement actions, and monetary fines each lower environmental employment. Extended model results provide evidence that these negative effects stem from the crowding out of facility managers’ intrinsic motivations.

This article examines the nature of imagination and of the realm called the imaginal by Henry Corbin and the Sufis. Referencing the works of Hermeticism, Gnosticism, Sufism, alchemy, and especially...

Junction temperature (TJ) control is mandatory to improve the optical efficiency, lifetime and the wavelength accuracy of the UV-C LED light sources. Thermoelectric cooler devices allow a critical control of the junction temperature, based on direct measurement of the solder point temperature. A PID control technique was implemented to control the voltage in the TEC devices and therefore the desired range of junction temperatures. The PID parameters are obtained with computational simulations based on physical models and experimental recordings of the solder temperature dynamics. Optical performance improves is demonstrated and the better lifetime could be achieved.