Healthcare utilization and behavior changes following workplace genetic testing at a large U.S. healthcare system.

PURPOSE: This study explored employee health behavior changes and healthcare utilization following workplace genetic testing (wGT). Wellness program-associated wGT seeks to improve employee health, but related health implications are unknown. METHODS: Employees of a large U.S. healthcare system offering wGT (cancer, heart disease, and pharmacogenomics - PGx) were sent electronic surveys. Self-reported data from those who received test results were analyzed. Descriptive statistics characterized responses, while logistic regression analyses explored correlates of responses to wGT. RESULTS: 53.9% (n=418/776) of respondents (88.3% female, mean age = 44 years) reported receiving wGT results. 12.0% (n=48/399) received results indicating increased risk (IR) of cancer, 9.5% (n=38/398) had IR of heart disease, and 31.4% (n=125/398) received informative PGx results. IR results for cancer and/or heart disease (n=67) were associated with health behavior changes (aOR 3.23; 95% CI 1.75, 6.13; p<0.001) and healthcare utilization (aOR 8.60; 95% CI 4.43, 17.5; p<0.001). Informative PGx results (n=125) were associated with medication changes (PGx - informative: 15.2%; PGx - uninformative: 4.8%; p=0.002). CONCLUSION: This study explored employee responses to wGT, contributing to the understanding of the ethical and social implications of wGT. Receiving IR results from wGT may promote health behavior changes and healthcare utilization in employees.

Genetic Researchers' Use of and Interest in Research With Diverse Ancestral Groups.

Importance: Genetic researchers must have access to databases populated with data from diverse ancestral groups to ensure research is generalizable or targeted for historically excluded communities. Objective: To determine genetic researchers' interest in doing research with diverse ancestral populations, which database stewards offer adequate samples, and additional facilitators for use of diverse ancestral data. Design, Setting, and Participants: This survey study was conducted from June to December 2022 and was part of an exploratory sequential mixed-methods project in which previous qualitative results informed survey design. Eligible participants included genetic researchers who held US academic affiliations and conducted research using human genetic databases. Exposure: Internet-administered survey to genetic research professionals. Main Outcomes and Measures: The survey assessed respondents' experience and interest in research with diverse ancestral data, perceptions of adequacy of diverse data across database stewards (ie, private, government, or consortia), and identified facilitators for encouraging use of diverse ancestral data. Descriptive statistics, χ2 tests, and z tests were used to describe respondents' perspectives and experiences. Results: A total of 294 researchers (171 men [58.5%]; 121 women [41.2%]) were included in the study, resulting in a response rate of 20.4%. Across seniority level, 109 respondents (37.1%) were senior researchers, 85 (28.9%) were mid-level researchers, 71 (24.1%) were junior researchers, and 27 (9.2%) were trainees. Significantly more respondents worked with data from European ancestral populations (261 respondents [88.8%]) compared with any other ancestral population. Respondents who had not done research with Indigenous ancestral groups (210 respondents [71.4%]) were significantly more likely to report interest in doing so than not (121 respondents [41.2%] vs 89 respondents [30.3%]; P < .001). Respondents reported discrepancies in the adequacy of ancestral populations with significantly more reporting European samples as adequate across consortium (203 respondents [90.6%]), government (200 respondents [89.7%]), and private (42 respondents [80.8%]) databases, compared with any other ancestral population. There were no significant differences in reported adequacy of ancestral populations across database stewards. A majority of respondents without access to adequate diverse samples reported that increasing the ancestral diversity of existing databases (201 respondents [68.4%]) and increasing access to databases that are already diverse (166 respondents [56.5%]) would increase the likelihood of them using a more diverse sample. Conclusions and Relevance: In this survey study of US genetic researchers, respondents reported existing databases only provide adequate ancestral samples for European populations, despite their interest in other ancestral populations. These findings suggest there are specific gaps in access to and composition of genetic databases, highlighting the urgent need to boost diversity in research samples to improve inclusivity in genetic research practices.

Characterising the social interaction style of autism in young adult males with fragile X syndrome.

BACKGROUND: The characterisation of autism in fragile X syndrome (FXS) has been a source of controversy due to the complexity of disentangling autism traits from common features of the FXS phenotype. Autism in FXS is significantly underdiagnosed in the community, which may be partly due to insufficient clinical description of the social interaction profile of autism within the FXS phenotype. In this study, we applied a classic framework for characterising social interaction styles in autism to a sample of young adult males with FXS and co-occurring autism to enhance understanding of how the social challenges associated with autism manifest within FXS. METHODS: Participants were 41 males (M age = 18 years) with FXS and co-occurring autism. Interaction samples were coded for expression of predominately 'active' (characterised by a desire to make social approaches) or 'passive' (characterised by lack of initiation of social approach towards others) interaction profiles. Differences in the expression of phenotypic features of FXS, including anxiety, attention-deficit/hyperactivity disorder, cognitive, adaptive and language impairments and autism symptom severity, were examined across those with passive and active interaction styles. RESULTS: Approximately half of the sample was classified as active and half as passive, demonstrating diversity in the social phenotype of autism associated with FXS. The two subtypes did not differ in autism severity, anxiety or attention-deficit/hyperactivity disorder symptoms or in cognitive, adaptive or language abilities. CONCLUSIONS: This study enhances understanding of FXS-associated autism by documenting phenotypic variability in the social interaction profile in this group, with active and passive social interaction styles represented. The two social interaction styles were not associated with differential expression of common phenotypic features of FXS, suggesting similar support needs.

Broadening the Perspective on Reducing Pharmaceutical Residues in the Environment.

The present study reviews options for reducing harm from pharmaceuticals that are known to cause adverse impacts by their presence in the environment. It reviews recent global and European Union policy development, which could go further in recognizing and addressing the issue in a global context. It considers green chemistry, which can help clean up production processes but holds only long-term promise for creating "green" alternatives. It explores the potential of health promotion and disease prevention, which can contribute significantly to a reduction of the disease burden and thus the need for medicines, both for infectious and for noncommunicable disease. Eco-directed sustainable prescribing practices are reviewed, which have been adopted successfully to reduce the use of harmful pharmaceuticals. We note recent developments in medicines optimization and precision medicine, which hold promise for improving patient outcomes, saving costs, and reducing pharmaceutical use, through individually tailored prescribing whereby the patient codecides their therapy. Waste prevention through reuse or redistribution is beginning to find public support and "take-back" waste disposal schemes set up via extended producer responsibility systems have achieved high returns. Finally, the paper summarizes preferred advanced wastewater technologies, including innovative low-cost, low-energy options. In summary, although end-of-pipe options have a role to play, particularly for highly concentrated wastewaters, solutions further up the medicinal chain and disease prevention interventions, informed by a broad view of health and health care, are needed to pursue a much greater potential reduction of pharmaceuticals in the environment than can be achieved by end-of-pipe solutions alone. Environ Toxicol Chem 2024;43:653-663. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A multi-national, video-based qualitative study to refine training guidelines for assigning an "unsafe" score in laparoscopic cholecystectomy critical view of safety.

BACKGROUND: The critical view of safety (CVS) was incorporated into a novel 6-item objective procedure-specific assessment for laparoscopic cholecystectomy (LC-CVS OPSA) to enhance focus on safe completion of surgical tasks and advance the American Board of Surgery's entrustable professional activities (EPAs) initiative. To enhance instrument development, a feasibility study was performed to elucidate expert surgeon perspectives regarding "safe" vs. "unsafe" practice. METHODS: A multi-national consortium of 11 expert LC surgeons were asked to apply the LC-CVS OPSA to ten LC videos of varying surgical difficulty using a "safe" vs. "unsafe" scale. Raters were asked to provide written rationale for all "unsafe" ratings and invited to provide additional feedback regarding instrument clarity. A qualitative analysis was performed on written responses to extract major themes. RESULTS: Of the 660 ratings, 238 were scored as "unsafe" with substantial variation in distribution across tasks and raters. Analysis of the comments revealed three major categories of "unsafe" ratings: (a) inability to achieve the critical view of safety (intended outcome), (b) safe task completion but less than optimal surgical technique, and (c) safe task completion but risk for potential future complication. Analysis of reviewer comments also identified the potential for safe surgical practice even when CVS was not achieved, either due to unusual anatomy or severe pathology preventing safe visualization. Based upon findings, modifications to the instructions to raters for the LC-CVS OPSA were incorporated to enhance instrument reliability. CONCLUSIONS: A safety-based LC-CVS OPSA has the potential to significantly improve surgical training by incorporating CVS formally into learner assessment. This study documents the perspectives of expert biliary tract surgeons regarding clear identification and documentation of unsafe surgical practice for LC-CVS and enables the development of training materials to improve instrument reliability. Learnings from the study have been incorporated into rater instructions to enhance instrument reliability.

Laparoscopic cholecystectomy critical view of safety (LC-CVS): a multi-national validation study of an objective, procedure-specific assessment using video-based assessment (VBA).

BACKGROUND: A novel 6-item objective, procedure-specific assessment for laparoscopic cholecystectomy incorporating the critical view of safety (LC-CVS OPSA) was developed to support trainee formative and summative assessments. The LC-CVS OPSA included two retraction items (fundus and infundibulum retraction) and four CVS items (hepatocystic triangle visualization, gallbladder-liver separation, cystic artery identification, and cystic duct identification). The scoring rubric for retraction consisted of poor (frequently outside of defined range), adequate (minimally outside of defined range) and excellent (consistently inside defined range) and for CVS items were "poor-unsafe", "adequate-safe", or "excellent-safe". METHODS: A multi-national consortium of 12 expert LC surgeons applied the OPSA-LC CVS to 35 unique LC videos and one duplicate video. Primary outcome measure was inter-rater reliability as measured by Gwet's AC2, a weighted measure that adjusts for scales with high probability of random agreement. Analysis of the inter-rater reliability was conducted on a collapsed dichotomous scoring rubric of "poor-unsafe" vs. "adequate/excellent-safe". RESULTS: Inter-rater reliability was high for all six items ranging from 0.76 (hepatocystic triangle visualization) to 0.86 (cystic duct identification). Intra-rater reliability for the single duplicate video was substantially higher across the six items ranging from 0.91 to 1.00. CONCLUSIONS: The novel 6-item OPSA LC CVS demonstrated high inter-rater reliability when tested with a multi-national consortium of LC expert surgeons. This brief instrument focused on safe surgical practice was designed to support the implementation of entrustable professional activities into busy surgical training programs. Instrument use coupled with video-based assessments creates novel datasets with the potential for artificial intelligence development including computer vision to drive assessment automation.

ACR Appropriateness Criteria® Tinnitus: 2023 Update.

Tinnitus is abnormal perception of sound and has many subtypes. Clinical evaluation, audiometry, and otoscopy should be performed before ordering any imaging, as the choice of imaging will depend on various factors. Type of tinnitus (pulsatile or nonpulsatile) and otoscopy findings of a vascular retrotympanic lesion are key determinants to guide the choice of imaging studies. High-resolution CT temporal bone is an excellent tool to detect glomus tumors, abnormal course of vessels, and some other abnormalities when a vascular retrotympanic lesion is seen on otoscopy. CTA or a combination of MR and MRA/MRV are used to evaluate arterial or venous abnormalities like dural arteriovenous fistula, arteriovenous malformation, carotid stenosis, dural sinus stenosis, and bony abnormalities like sigmoid sinus wall abnormalities in cases of pulsatile tinnitus without a vascular retrotympanic lesion. MR of the brain is excellent in detecting mass lesions such as vestibular schwannomas in cases of unilateral nonpulsatile tinnitus. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Arterial resection during operative management of pancreatic head and uncinate process adenocarcinoma: a systematic review.

Background: Surgical resection is a part of the treatment pathways for the management of pancreatic cancer with arterial involvement. Arterial resection in this context is however not widely supported due to the paucity and diversity of the reported evidence in the literature. The aim of this systematic review is the presentation and analysis of the current evidence in the field. Methods: A systematic literature search of PubMed, MEDLINE and the Cochrane Library was performed for eligible studies, following the PRISMA guidelines. Information on baseline characteristics, peri-operative outcomes, survival outcomes and histopathological findings were extracted for pooling and analysis. Results: Eight studies with a total of 170 patients were included in the analysis. One hundred and thirty-five patients had a pancreaticoduodenectomy (PD) and 35 had a total pancreatectomy (TP) with arterial resection. Perioperative morbidity was 43.5% and mortality was 4.5%. Median overall survival (OS) was 12.7 months (range, 10.5-22.2 months). Overall 3- and 5-year survival for this cohort was reported at 6.6% (range, 0-42.4%) and 3.3% (range, 0-6.6%) respectively. Resection margins were clear (R0) in a median of 75% of patients. Only a median of 45% of patients received neo-adjuvant chemotherapy. Conclusions: Arterial resection can be performed with an acceptable peri-operative morbidity and mortality. However, survival outcomes are still not convincing and future efforts should concentrate on patient and disease biology selection.

The reliability of a portable steam sauna pod for the whole-body passive heating of humans.

INTRODUCTION: Passive heating is receiving increasing attention within human performance and health contexts. A low-cost, portable steam sauna pod may offer an additional tool for those seeking to manipulate physiological (cardiovascular, thermoregulatory and sudomotor) and perceptual responses for improving sporting or health profiles. This study aimed to 1) report the different levels of heat stress and determine the pods' inter-unit reliability, and 2) quantify the reliability of physiological and perceptual responses to passive heating. METHOD: In part 1, five pods were assessed for temperature and relative humidity (RH) every 5 min across 70 min of heating for each of the 9 settings. In part 2, twelve males (age: 24 ± 4 years) completed two 60 min trials of passive heating (3 × 20 min at 44 °C/99% RH, separated by 1 week). Heart rate (HR), rectal (Trectal) and tympanic temperature (Ttympanic) were recorded every 5 min, thermal comfort (Tcomfort) and sensation (Tsensation) every 10 min, mean arterial pressure (MAP) at each break period and sweat rate (SR) after exiting the pod. RESULTS: In part 1, setting 9 provided the highest temperature (44.3 ± 0.2 °C) and longest time RH remained stable at 99% (51±7 min). Inter-unit reliability data demonstrated agreement between pods for settings 5-9 (intra-class correlation [ICC] >0.9), but not for settings 1-4 (ICC <0.9). In part 2, between-visits, high correlations, and low typical error of measurement (TEM) and coefficient of variation (CV) were found for Trectal, HR, MAP, SR, and Tcomfort, but not for Ttympanic or Tsensation. A peak Trectal of 38.09 ± 0.30 °C, HR of 124 ± 15 b min-1 and a sweat loss of 0.73 ± 0.33 L were reported. No between-visit differences (p > 0.05) were observed for Trectal, Ttympanic, Tsensation or Tcomfort, however HR (+3 b.min-1) and MAP (+4 mmHg) were greater in visit 1 vs. 2 (p < 0.05). CONCLUSION: Portable steam sauna pods generate reliable heat stress between-units. The highest setting (44 °C/99% RH) also provides reliable but modest adjustments in physiological and perceptual responses.

Assessment of the Needs of Nephrology Divisions to Implement Return of Clinically Significant Research Genetic Results: A Survey of Nephrotic Syndrome Study Network (NEPTUNE) Investigators.

Introduction: There is an increasing need to return genetic testing results to patients with kidney disease who were first genotyped on a research basis. Operationalizing this process in nephrology clinics is challenged by a limited number of genetic providers with whom to partner and a general lack of support services for all clinicians. Methods: We administered a survey in March 2022 to assess the current ability and ongoing needs of nephrology divisions to return clinically significant research genetic results to patients and to implement clinical genetic testing. This survey was distributed to institutions within the Nephrotic Syndrome Study Network (NEPTUNE) as part of the planning process for return of research genetic results to participants with pathogenic variants in Mendelian nephrotic syndrome genes. Results: Twenty-seven of 28 sites (96%) completed the survey. 59% (n = 16) of sites said they could handle return of research genetic results independently, with the rest expressing hesitation about the volume and complexity of patients and the limited resources and access to genetics services. 81% (n = 22) of these institutions did have a genetics clinic and 26% (n = 7) have a nephrology genetics clinic. However, 70% (n = 10) of these clinics have a waiting time over 1 month. 89% of divisions (n = 24) were conducting genetic testing and 96% of those (n = 23) used a kidney multi-gene panel. In 46% of divisions (n = 11), nephrologists were handling logistics of obtaining genetic testing samples themselves. Conclusion: We identified specific areas of support needed for return of clinically significant genetic results from research studies. While the surveyed nephrologists were conducting genetic testing, there were limitations in the support services available. This survey will help guide other research studies that wish to return genetic results to participants and also highlight the need for increasing support to effectively operationalize genetic testing in nephrology clinics.

Altered motility in response to iron-limitation is regulated by lpdA in uropathogenic E. coli CFT073.

More than half of all women will experience a urinary tract infection (UTI) in their lifetime with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored, despite the lack of free iron available in the host. Therefore, we sought to explore the potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, in media containing an iron chelator. Under iron limitation, CFT073 had elevated fliC (flagella) promoter activity, driving motility on the leading edge of the colony. Furthermore, this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagella expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. To define the regulatory mechanism, we constructed single knockouts of eight master regulators. The iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three transcription factors. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in an lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI. Collectively, we demonstrated that iron-mediated motility in CFT073 is regulated by lpdA , which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. Importance: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic E. coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism, and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic resistant pathogens.

Early postoperative risk stratification in patients with pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: Early stratification of postoperative pancreatic fistula according to severity and/or need for invasive intervention may improve outcomes after pancreaticoduodenectomy. This study aimed to identify the early postoperative variables that may predict postoperative pancreatic fistula severity. METHODS: All patients diagnosed with biochemical leak and clinically relevant-postoperative pancreatic fistula based on drain fluid amylase >300 U/L on the fifth postoperative day after pancreaticoduodenectomy were identified from a consecutive cohort from Birmingham, UK. Demographics, intraoperative parameters, and postoperative laboratory results on postoperative days 1 through 7 were retrospectively extracted. Independent predictors of clinically relevant-postoperative pancreatic fistula were identified using multivariable binary logistic regression and converted into a risk score, which was applied to an external cohort from Verona, Italy. RESULTS: The Birmingham cohort had 187 patients diagnosed with postoperative pancreatic fistula (biochemical leak: 99, clinically relevant: 88). In clinically relevant-postoperative pancreatic fistula patients, the leak became clinically relevant at a median of 9 days (interquartile range: 6-13) after pancreaticoduodenectomy. Male sex (P = .002), drain fluid amylase-postoperative day 3 (P < .001), c-reactive protein postoperative day 3 (P < .001), and albumin-postoperative day 3 (P = .028) were found to be significant predictors of clinically relevant-postoperative pancreatic fistula on multivariable analysis. The multivariable model was converted into a risk score with an area under the receiver operating characteristic curve of 0.78 (standard error: 0.038). This score significantly predicted the need for invasive intervention (postoperative pancreatic fistula grades B3 and C) in the Verona cohort (n = 121; area under the receiver operating characteristic curve: 0.68; standard error = 0.06; P = .006) but did not predict clinically relevant-postoperative pancreatic fistula when grades B1 and B2 were included (area under the receiver operating characteristic curve 0.52; standard error = 0.07; P = .802). CONCLUSION: We developed a novel risk score based on early postoperative laboratory values that can accurately predict higher grades of clinically relevant-postoperative pancreatic fistula requiring invasive intervention. Early identification of severe postoperative pancreatic fistula may allow earlier intervention.

A Pilot Randomized Trial of a Purposeful and Stimulating Volunteer Opportunity: Program Satisfaction and Potential Impacts on Perceived Cognitive Change in a Neurologically Mixed Sample of Older Adults.

BACKGROUND: Purposeful social interactions are important for healthy aging. We conducted a pilot trial of SPEAK! (Seniors Promoting English Acquisition and Knowledge), an intervention providing older volunteers with a safe, accessible opportunity to converse via webcam with English-language learners. METHODS: A neurologically mixed sample of older adults was randomized to 8 weekly, webcam conversations with English-language learners or a waitlist control. Outcomes included the Cognitive Change Index (CCI) and surveys of program satisfaction. Here, we report on session completion, intervention satisfaction, and follow-up CCI scores. Exploratory analyses of CCI intervention effects controlled for baseline CCI scores and the interaction between group and baseline CCI. RESULTS: Participants (N=38) were on average 70.8 years of age, 28/38 were White, and 16/38 demonstrated possible cognitive impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pairs completed 115/136 sessions (85%) and all volunteers said they would recommend the program. Controlling for the interaction between baseline CCI and randomization group, SPEAK! volunteers had better follow-up CCI scores than controls (P=0.018). Improvements in CCI were greater among participants with fewer baseline memory problems. CONCLUSIONS: SPEAK! was feasible and appreciated by older adults with and without cognitive impairment. Larger studies should confirm benefits for memory and other determinants of quality of life.

Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study.

PURPOSE: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8, and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles. RESULTS: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue. CONCLUSION: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.

Genomic testing in voluntary workplace wellness programs in the US: Evidence and challenges.

BACKGROUND: Workplace genetic and/or genomic testing (wGT) is one of many options that employers can offer within the scope of voluntary workplace wellness programs, though we know little about how many employers are offering this benefit, or what kinds of testing are included. METHODS: Our landscaping review sought to discover the prevalence and distribution of wGT within voluntary wellness programs among U.S. companies using three approaches: (1) analysis of publicly available information; (2) national surveys; and (3) interviews with company representatives. RESULTS: In total, 50/420 (11.9%) companies we investigated had publicly available data suggesting that they offer wGT to their employees. Survey data weighted to be representative of the type and distribution of U.S. companies suggest that ~1% of U.S. companies offer wGT to their employees. CONCLUSION: Our research found little evidence of broad uptake of wGT among U.S. companies, though information gathering was challenging.

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency.

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/- rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/- rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/- males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).

Significance of predicted future liver remnant volume on liver failure risk after major hepatectomy: a case matched comparative study.

Introduction: Future liver remnant volume (FLRV), a risk factor for liver failure (PHLF) after major hepatectomy (MH), is not routinely measured. This study aimed to evaluate the association between FLRV and PHLF. Patients and methods: All patients undergoing MH (4 + segments) between 2011 and 2018 were identified from a prospectively maintained single-centre database. Perioperative data were collected for patients with PHLF, who were matched (1:2) with non-PHLF controls. FLRV and FLRV% (i.e., % of total liver volume) were calculated retrospectively from preoperative CT scans using Synapse-3D software, and compared between the PHLF and matched control groups. Results: Of 711 patients undergoing MH, PHLF occurred in 27 (3.8%), of whom 24 had preoperative CT scans available. These patients were matched to 48 non-PHLF controls, 98% of whom were classified as being at high risk of PHLF on preoperative risk scoring. FLRV% was significantly lower in the PHLF group, compared to matched controls (median: 28.7 vs. 35.2%, p = 0.010), with FLRV% < 30% in 58% and 29% of patients, respectively. Assessment of the ability of FLRV% to differentiate between PHLF and matched controls returned an area under the ROC curve of 0.69, and an optimal cut-off value of FLRV% < 31.5%, which yielded 79% sensitivity and 67% specificity. Conclusions: FLRV% is significantly predictive of PHLF after MH, with over half of patients with PHLF having FLRV% < 30%. In light of this, we propose that all patients should undergo risk stratification prior to MH, with the high risk patients additionally being assessed with CT volumetry.

Calamities causing loss of museum collections: a historical and global perspective on museum disasters.

With alarming frequency, significant collections in natural history museums have been destroyed or damaged through insurrections, cyclones, wars, fires, floods, or earthquakes particularly in the nineteenth century but continuing into the twentieth century with World War II bombings, fires, and earthquakes being the primary causes of loss in fifty-seven institutions across thirty countries. We review the loss or damage of museum collections globally, and their varied causes. We emphasize the benefits of dispersal of a sample of paratypes across institutions as an essential feature of taxonomic practice. We argue that museums do not own type material but are acting as perpetual custodians of type material on behalf of science and society in general, and that museums, therefore, have an obligation to minimize the risk to their collections. The significance of the loss of type material would be ameliorated if, when there are numerous paratypes or syntypes, members of a type series were distributed among several institutions. This is currently common practice but historically this was not always the case and might not be possible if only a single holotype is available. We also reaffirm the need for scientists around the globe to develop specific protocols to protect collections of biological and cultural materials from loss or damage from natural and human-created disasters now and into the future. We comment on recent moves to modify the Zoological Code of Nomenclature to allow the use of images as "type" material when describing new species with the image serving as a substitute for "physical" specimens deposited in museum collections. Although our focus is on herpetological collections, our particular interest and area of expertise, our observations apply broadly to all collections, including those of animals, plants, and anthropological or ethnographic material.