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Objective To report our successful outcomes of genital split-thickness skin graft (STSG) in covering major skin loss and providing good functional and cosmetic outcomes. Materials and Methods A retrospective chart review was performed for all adult urology patients who underwent STSG at our institution from 1998 to 2014. Patients had a wide range of disease etiologies, including tissue loss (eg post-Fournier's gangrene), lymphedema, buried penis, foreign body injection, and tumors. Results A total of 54 patients were identified with the following breakdown of etiology: 13 patients with tissue loss (eg post-Fournier's gangrene), 13 with lymphedema, 12 with buried penis, 8 with foreign body injection, 4 with hidradenitis suppurativa, and 4 with tumors. Fifty-two out of 54 patients had more than 90% graft take, with maintained or improved erection, normal voiding, good cosmetic outcome as judged by the patient and the examining surgeon, and normal mobility. One patient died at 3 months due to cardiovascular cause, and 1 patient had a poor take of the graft. Conclusion We show the wide variety of indications for STSG use, the ease of the technique, and its successful outcomes. We believe this procedure should be offered to patients as a first-line treatment and also as a last resort when other more conservative approaches fail.

Objective To evaluate the correlation between the International Prostate Symptom Score (IPSS) and the Visual Prostate Symptom Score (VPSS), a visual assessment of urinary stream, frequency, nocturia, and quality of life using pictograms, in a health safety net population. Methods Men presenting to San Francisco General Hospital with lower urinary tract symptoms completed the IPSS and the VPSS without and then with assistance. Statistical analysis was performed using the chi-square test, the Wilcoxon signed rank test, and the Spearman rank correlation. Results One hundred twenty-one patients were enrolled between December 2013 and May 2014 with a mean age of 54 years. There were statistically significant correlations between total VPSS and total IPSS (ρ = 0.71; P

Objective To determine national urethroplasty trends based on type of surgery and patient and hospital characteristics. We hypothesized that the number of complex urethroplasty procedures performed has increased over time and may be associated with increased periprocedure complications. Methods The National Inpatient Sample from years 2000 to 2010 was queried for patients with urethroplasty-associated International Classification of Diseases, Ninth Revision, Clinical Modification codes. We analyzed trends in urethroplasty procedures, patient demographics, comorbidities, and hospital characteristics. We evaluated the relationship between patient demographics and comorbid disease, length of hospital stay, hospital charges, and inpatient complications. Results During the study period, an estimated 13,700 men (95% confidence interval, 9507-17,894) underwent urethroplasty nationally. Excision with primary anastomosis, buccal graft, and other graft or flap urethroplasty comprised 80.3%, 14.3%, and 5.4%, respectively. Buccal mucosa graft procedures increased over time (P =.03). Only 1.6% of hospitals have ≥20 urethroplasties performed annually. Urethroplasty type and urethroplasty volume were not associated with immediate complication rates. Hypertension, diabetes, chronic pulmonary disease, and obesity were the most common comorbidities in urethroplasty patients. Complications during urethroplasty hospitalization occurred in 6.6% of men, with surgical or wound complications being the most common (5.2%). Postoperative mortality was exceedingly rare. Older patients, African Americans, and patients with increased comorbidities were more likely to have complications. Conclusion An increasing number of buccal mucosa graft urethroplasties occurred over time. Urethroplasty patients have low immediate perioperative morbidity (6.6%) and mortality (0.07%). Patients who are older, African American, or have more comorbid conditions have greater risk for complications.

Aim: Pubic hair grooming is a common practice in the United States and coincides with prevalence of grooming-related injuries. Men who have sex with men (MSM) groom more frequently than men who have sex with women (MSW). We aim to characterize the influence of sexual orientation and sexual role on grooming behavior, injuries, and infections in men in the United States. Methods: We conducted a nationally representative survey of noninstitutionalized adults aged 18-65 residing in the United States. We examined the prevalence and risk factors of injuries and infections that occur as a result of personal grooming. Results: Of the 4,062 men who completed the survey, 3,176 (78.2%) report having sex with only women (MSW), 198 (4.9%) report sex with men (MSM), and 688 (16.9%) report not being sexually active. MSM are more likely to groom (42.5% vs. 29.0%, P

Introduction: We characterize comorbidities and inpatient complications of patients with lichen sclerosus who underwent urethroplasty from a large national patient data source. Methods: We queried the Nationwide Inpatient Sample for patients who underwent urethroplasty between 2000 and 2010. We compared demographics, comorbidities, complications, length of hospital stay and hospital charges for patients with and without the diagnosis of lichen sclerosus. Results: An estimated 13,700 urethroplasties were performed in the United States during the study period. Patients with lichen sclerosus comprised an estimated 3.8% of the urethroplasty population. The majority of patients with urethral stricture with lichen sclerosus were Caucasian (84%) and older, with 63% age 45 or older. Chronic hypertension, diabetes mellitus, rheumatoid arthritis/collagen vascular disease and obesity were associated with increased odds of having a lichen sclerosus diagnosis. The central East Coast (7.2%) and the Pacific Northwest (6.3%) had the highest percentage of patients treated with urethroplasty with lichen sclerosus. Patients with lichen sclerosus had longer hospital stays than those without lichen sclerosus (3.5 vs 2.6 days, p

The purpose of this study was to compare the clinical root coverage achieved with two connective tissue grafts that were removed from the same donor area at different times and used in subepithelial grafts for root coverage. Sixty patients, each of whom had two connective tissue grafts removed from the same donor area at different times, were included in this study. The connective tissue grafts were used in two different subepithelial grafts for root coverage. The subepithelial grafts with both the first and second connective tissue grafts produced statistically significant changes in recession, probing depth, width of keratinized tissue, and attachment level. The changes obtained in the clinical measurements were not statistically significantly different between the first and second connective tissue grafts. The mean percentages of root coverage with the first and second connective tissue grafts were 95.4% and 98.2%, respectively, a statistically significant difference. None of the factors evaluated (sex, age, smoking history, and time between the two surgeries) could be related to statistically significant differences in the mean root coverage obtained. In this study, the second connective tissue graft produced greater mean root coverage than the first connective tissue graft. [ABSTRACT FROM AUTHOR]

The goal of this study was to evaluate the clinical changes obtained when intra-bony defects were treated with an enamel matrix derivative (EMD), a bone graft, and guided tissue regeneration. Fifty patients with a periodontal defect not associated with a furcation and with an attachment loss of at least 7.0 mm were included in this study. Full-thickness flaps were reflected, the roots were planed, EMD was applied, a demineralized freeze-dried bone allograft combined with EMD was placed, a bioabsorbable membrane was placed, and more EMD was applied. The defect areas were then sutured. At a mean of 5.3 months after treatment, there was a mean increase in recession of 0.7 mm, a mean reduction in probing depth of 5.7 mm, and a mean gain in attachment level of 5.0 mm. In this study there was more recession in smokers than in nonsmokers and in defects associated with anterior teeth. Additionally, the deeper defects (those with greater probing depths and attachment level loss) had the greatest reductions in probing depth and gains in attachment level. Based on this study, this technique proved itself to be an effective method to improve the clinical situation when treating periodontal defects not involving furcations. [ABSTRACT FROM AUTHOR]

William Shakespeare’s comedy, Much Ado About Nothing, and Paul Laurence Dunbar’s poem, “Sympathy,” peer through black naturalism’s socially deterministic lens, despite conflicts in time, geopolitics, social norms, and literary imagination. Specifically, Don John’s truculent reference about “sing[ing] in his cage” (1.3.32) inspired investigation into whether Dunbar’s famed line, “I know why the caged bird sings” (21), intentionally alludes to Shakespeare’s work. While the research is inconclusive, the references provide clarity for Don John’s character particularly. Essentially, Don John’s foolhardy evil meets society’s standards for masking social truths, just as Dunbar’s poem has been reduced to a sweet and imaginative ditty over time. Thus, this article broadly explores society’s tendency to recycle oppression under expedient pretenses. Although Don John self-proclaims inherent evil, closer scrutiny of his figurative scar – coat of arms, representing illegitimacy – reveals a socially determined position, more consistent with Dunbar’s second-rate life based on skin color and his naturalism based on whiteness. Because Mowat and Werstine suggest that Don John’s ill-intentioned behaviors are less about biology (blood) than impassioned human response to social injustice (Blood), naturalism links the unlikely pair. As such, the article uses Dunbar’s black naturalism to exemplify societal “caging” in Much Ado and “Sympathy.”

Emergency departments (EDs) frequently evaluate and manage patients with drug toxicity. One of the most challenging aspects of this management is the cardiovascular effects. This article describes some of the most common overdoses involving several prescription medications and the currently most popular abused sympathomimetic drugs. Copyright © 2000 by Aspen Publishers, Inc. [ABSTRACT FROM AUTHOR]

Abstract Background The mammalian target of rapamycin protein (mTOR) is an evolutionarily conserved kinase that regulates protein synthesis, cell cycle progression and proliferation in response to various environmental cues. As a critical downstream mediator of PI3K signaling, mTOR is important for lymphocyte development and function of mature T and B-cells. Most studies of mTOR in immune responses have relied on the use of pharmacological inhibitors, such as rapamycin. Rapamycin-FKBP12 complex exerts its immunosuppressive and anti-proliferative effect by binding outside the kinase domain of mTOR, and subsequently inhibiting downstream mTOR signaling. Results To determine the requirement for mTOR kinase activity in the immune system function, we generated knock-in mice carrying a mutation (D2338) in the catalytic domain of mTOR. While homozygous mTOR kd/kd embryos died before embryonic day 6.5, heterozygous mTOR+/kd mice appeared entirely normal and are fertile. mTOR +/kd mice exhibited normal T and B cell development and unaltered proliferative responses of splenocytes to IL-2 and TCR/CD28. In addition, heterozygousity for the mTOR kinase-dead allele did not sensitize T cells to rapamycin in a CD3-mediated proliferation assay. Unexpectedly, mTOR kinase activity towards its substrate 4E-BP1 was not decreased in hearts and livers from heterozygous animals. Conclusion Altogether, our findings indicate that mTOR kinase activity is indispensable for the early development of mouse embryos. Moreover, a single wild type mTOR allele is sufficient to maintain normal postnatal growth and lymphocyte development and proliferation.

Spatially resolved molecular assays provide high dimensional genetic, transcriptomic, proteomic, and epigenetic information in situ and at various resolutions. Pairing these data across modalities with histological features enables powerful studies of tissue pathology in the context of an intact microenvironment and tissue structure. Increasing dimensions across molecular analytes and samples require new data science approaches to functionally annotate spatially resolved molecular data. A specific challenge is data-driven cross-sample domain detection that allows for analysis within and between consensus tissue compartments across high volumes of multiplex datasets stemming from tissue atlasing efforts. Here, we present MILWRM (multiplex image labeling with regional morphology)-a Python package for rapid, multi-scale tissue domain detection and annotation at the image- or spot-level. We demonstrate MILWRM's utility in identifying histologically distinct compartments in human colonic polyps, lymph nodes, mouse kidney, and mouse brain slices through spatially-informed clustering in two different spatial data modalities from different platforms. We used tissue domains detected in human colonic polyps to elucidate the molecular distinction between polyp subtypes, and explored the ability of MILWRM to identify anatomical regions of the brain tissue and their respective distinct molecular profiles., (© 2024. The Author(s).)

Fish gut microbial communities are important for the breakdown and energy harvesting of the host diet. Microbes within the fish gut are selected by environmental and evolutionary factors. To understand how fish gut microbial communities are shaped by diet, three tropical fish species (hawkfish, Paracirrhites arcatus ; yellow tang, Zebrasoma flavescens ; and triggerfish, Rhinecanthus aculeatus ) were fed piscivorous (fish meal pellets), herbivorous (seaweed), and invertivorous (shrimp) diets, respectively. From fecal samples, a total of 43 metagenome assembled genomes (MAGs) were recovered from all fish diet treatments. Each host-diet treatment harbored distinct microbial communities based on taxonomy, with Proteobacteria, Bacteroidota, and Firmicutes being the most represented. Based on their metagenomes, microbial communities from all three host-diet treatments demonstrated a baseline ability to degrade proteinaceous, fatty acid, and simple carbohydrate inputs and carry out central carbon metabolism, lactate and formate fermentation, acetogenesis, nitrate respiration, and B vitamin synthesis. The herbivorous yellow tang harbored a more functionally diverse microbial community with some complex polysaccharide degradation specialists, while the piscivorous hawkfish's gut community was more specialized for the degradation of proteins. The invertivorous triggerfish's gut microbiome lacked many carbohydrate degrading capabilities, resulting in a more specialized, functionally uniform community. Across all treatments, several MAGs were able to participate in only individual steps of the degradation of complex polysaccharides, suggestive of microbial community networks that degrade complex inputs. These data suggest the existence of a functional core microbiome that is common among fish species, although the specific taxonomic identities of the associated bacteria may differ.

The Permian Basin, underlying southeast New Mexico and west Texas, is one of the most productive oil and gas (OG) provinces in the United States. Oil and gas production yields large volumes of wastewater with complex chemistries, and the environmental health risks posed by these OG wastewaters on sensitive desert ecosystems are poorly understood. Starting in November 2017, 39 illegal dumps, as defined by federal and state regulations, of OG wastewater were identified in southeastern New Mexico, releasing ~600,000 L of fluid onto dryland soils. To evaluate the impacts of these releases, we analyzed changes in soil geochemistry and microbial community composition by comparing soils from within OG wastewater dump-affected samples to unaffected zones. We observed significant changes in soil geochemistry for all dump-affected compared with control samples, reflecting the residual salts and hydrocarbons from the OG-wastewater release (e.g., enriched in sodium, chloride, and bromide). Microbial community structure significantly ( P < 0.01) differed between dump and control zones, with soils from dump areas having significantly ( P < 0.01) lower alpha diversity and differences in phylogenetic composition. Dump-affected soil samples showed an increase in halophilic and halotolerant taxa, including members of the Marinobacteraceae, Halomonadaceae, and Halobacteroidaceae, suggesting that the high salinity of the dumped OG wastewater was exerting a strong selective pressure on microbial community structure. Taxa with high similarity to known hydrocarbon-degrading organisms were also detected in the dump-affected soil samples. Overall, this study demonstrates the potential for OG wastewater exposure to change the geochemistry and microbial community dynamics of arid soils.IMPORTANCEThe long-term environmental health impacts resulting from releases of oil and gas (OG) wastewater, typically brines with varying compositions of ions, hydrocarbons, and other constituents, are understudied. This is especially true for sensitive desert ecosystems, where soil microbes are key primary producers and drivers of nutrient cycling. We found that releases of OG wastewater can lead to shifts in microbial community composition and function toward salt- and hydrocarbon-tolerant taxa that are not typically found in desert soils, thus altering the impacted dryland soil ecosystem. Loss of key microbial taxa, such as those that catalyze organic carbon cycling, increase arid soil fertility, promote plant health, and affect soil moisture retention, could result in cascading effects across the sensitive desert ecosystem. By characterizing environmental changes due to releases of OG wastewater to soils overlying the Permian Basin, we gain further insights into how OG wastewater may alter dryland soil microbial functions and ecosystems., Competing Interests: The authors declare no conflict of interest.

One in three people globally are challenged to live on hazardous, unsanitary water, and this relates to higher risks of death and development of diseases. According to scientific research, activated charcoal can be used to clean water contaminants to help make water safer.•Carbonization: this study demonstrates an inexpensive method of producing activated charcoal that can be performed in any setting using locally available biomass materials.•Activation: thermal air oxidation between moderate temperatures of 450-550 °C. Our data indicate that this technique produces charcoal with an adsorptive capacity near to that of commercial-grade charcoal as demonstrated by spectrophotometric analysis. This simple approach to charcoal activation may benefit rural communities where sources of sanitary water are low or nonexistent., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Drinking water supplies across the United States have been contaminated by firefighting and fire-training activities that use aqueous film-forming foams (AFFF) containing per- and polyfluoroalkyl substances (PFAS). Much of the AFFF is manufactured using electrochemical fluorination by 3M. Precursors with six perfluorinated carbons (C6) and non-fluorinated amine substituents make up approximately one-third of the PFAS in 3M AFFF. C6 precursors can be transformed through nitrification (microbial oxidation) of amine moieties into perfluorohexane sulfonate (PFHxS), a compound of regulatory concern. Here, we report biotransformation of the most abundant C6 sulfonamido precursors in 3M AFFF with available commercial standards (FHxSA, PFHxSAm, and PFHxSAmS) in microcosms representative of the groundwater/surface water boundary. Results show rapid (<1 day) biosorption to living cells by precursors but slow biotransformation into PFHxS (1-100 pM day -1 ). The transformation pathway includes one or two nitrification steps and is supported by the detection of key intermediates using high-resolution mass spectrometry. Increasing nitrate concentrations and total abundance of nitrifying taxa occur in parallel with precursor biotransformation. Together, these data provide multiple lines of evidence supporting microbially limited biotransformation of C6 sulfonamido precursors involving ammonia-oxidizing archaea ( Nitrososphaeria ) and nitrite-oxidizing bacteria ( Nitrospina ). Further elucidation of interrelationships between precursor biotransformation and nitrogen cycling in ecosystems would help inform site remediation efforts.

Background: Pelvic fracture urethral injury (PFUI) occurs in up to 10% of pelvic fractures. There is mixed evidence supporting early endoscopic urethral realignment (EUR) over suprapubic tube (SPT) placement and delayed urethroplasty. Some studies show decreased urethral obstruction with EUR, while others show few differences. We hypothesized that EUR would reduce the rate of urethral obstruction after PFUI., Methods: Twenty-six US medical centers contributed patients following either an EUR or SPT protocol from 2015 to 2020. If retrograde cystoscopic catheter placement failed, patients were included and underwent either EUR or SPT placement based on their institution's assigned treatment arm. Endoscopic urethral realignment involved simultaneous antegrade/retrograde cystoscopy to place a catheter across the urethral injury. The primary endpoint was development of urethral obstruction. Fisher's exact test was used to analyze the relationship between PFUI management and development of urethral obstruction., Results: There were 106 patients with PFUI; 69 (65%) had complete urethral disruption and failure of catheter placement with retrograde cystoscopy. Of the 69 patients, there were 37 (54%) and 32 (46%) in the EUR and SPT arms, respectively. Mean age was 37.0 years (SD, 16.3 years) years, and mean follow-up was 463 days (SD, 280 days) from injury. In the EUR arm, 36 patients (97%) developed urethral obstruction compared with 30 patients (94%) in the SPT arm ( p = 0.471). Urethroplasty was performed in 31 (87%) and 29 patients (91%) in the EUR and SPT arms, respectively ( p = 0.784)., Conclusion: In this prospective multi-institutional study of PFUI, EUR was not associated with a lower rate of urethral obstruction or need for urethroplasty when compared with SPT placement. Given the potential risk of EUR worsening injuries, clinicians should consider SPT placement as initial treatment for PFUI when simple retrograde cystoscopy is not successful in placement of a urethral catheter., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine patient outcomes across a range of pelvic fracture urethral injury (PFUI) severity. PFUI is a devastating consequence of a pelvic fracture. No study has stratified PFUI outcomes based on severity of the urethral distraction injury., Methods: Adult male patients with blunt-trauma-related PFUI were followed prospectively for a minimum of six months at 27 US medical centers from 2015-2020. Patients underwent retrograde cystourethroscopy and retrograde urethrography to determine injury severity and were categorized into three groups: (1) major urethral distraction, (2) minor urethral distraction, and (3) partial urethral injury. Major distraction vs minor distraction was determined by the ability to pass a cystoscope retrograde into the bladder. Simple statistics summarized differences between groups. Multi-variable analyses determined odds ratios for obstruction and urethroplasty controlling for urethral injury type, age, and Injury Severity Score., Results: There were 99 patients included, 72(72%) patients had major, 13(13%) had minor, and 14(14%) had partial urethral injuries. The rate of urethral obstruction differed in patients with major (95.8%), minor (84.6%), and partial injuries (50%) (P < 0.001). Urethroplasty was performed in 90% of major, 66.7% of minor, and 35.7% of partial injuries (P < 0.001)., Conclusion: In PFUI, a spectrum of severity exists that influences outcomes. While major and minor distraction injuries are associated with a higher risk of developing urethral obstruction and need for urethroplasty, up to 50% of partial PFUI will result in obstruction, and as such need to be closely followed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A fundamental goal of scientific research is to generate true positives (i.e., authentic discoveries). Statistically, a true positive is a significant finding for which the underlying effect size (δ) is greater than 0, whereas a false positive is a significant finding for which δ equals 0. However, the null hypothesis of no difference (δ = 0) may never be strictly true because innumerable nuisance factors can introduce small effects for theoretically uninteresting reasons. If δ never equals zero, then with sufficient power, every experiment would yield a significant result. Yet running studies with higher power by increasing sample size (N) is one of the most widely agreed upon reforms to increase replicability. Moreover, and perhaps not surprisingly, the idea that psychology should attach greater value to small effect sizes is gaining currency. Increasing N without limit makes sense for purely measurement-focused research, where the magnitude of δ itself is of interest, but it makes less sense for theory-focused research, where the truth status of the theory under investigation is of interest. Increasing power to enhance replicability will increase true positives at the level of the effect size (statistical true positives) while increasing false positives at the level of theory (theoretical false positives). With too much power, the cumulative foundation of psychological science would consist largely of nuisance effects masquerading as theoretically important discoveries. Positive predictive value at the level of theory is maximized by using an optimal N, one that is neither too small nor too large., (© 2022. The Psychonomic Society, Inc.)

Motivation: Multiplexed imaging is a nascent single-cell assay with a complex data structure susceptible to technical variability that disrupts inference. These in situ methods are valuable in understanding cell-cell interactions, but few standardized processing steps or normalization techniques of multiplexed imaging data are available., Results: We implement and compare data transformations and normalization algorithms in multiplexed imaging data. Our methods adapt the ComBat and functional data registration methods to remove slide effects in this domain, and we present an evaluation framework to compare the proposed approaches. We present clear slide-to-slide variation in the raw, unadjusted data and show that many of the proposed normalization methods reduce this variation while preserving and improving the biological signal. Furthermore, we find that dividing multiplexed imaging data by its slide mean, and the functional data registration methods, perform the best under our proposed evaluation framework. In summary, this approach provides a foundation for better data quality and evaluation criteria in multiplexed imaging., Availability and Implementation: Source code is provided at: https://github.com/statimagcoll/MultiplexedNormalization and an R package to implement these methods is available here: https://github.com/ColemanRHarris/mxnorm., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)

The widespread application of directional drilling and hydraulic fracturing technologies expanded oil and gas (OG) development to previously inaccessible resources. A single OG well can generate millions of liters of wastewater, which is a mixture of brine produced from the fractured formations and injected hydraulic fracturing fluids (HFFs). With thousands of wells completed each year, safe management of OG wastewaters has become a major challenge to the industry and regulators. OG wastewaters are commonly disposed of by underground injection, and previous research showed that surface activities at an Underground Injection Control (UIC) facility in West Virginia affected stream biogeochemistry and sediment microbial communities immediately downstream from the facility. Because microbially driven processes can control the fate and transport of organic and inorganic components of OG wastewater, we designed a series of aerobic microcosm experiments to assess the influence of high total dissolved solids (TDS) and two common HFF additives-the biocide 2,2-dibromo-3-nitrilopropionamide (DBNPA) and ethylene glycol (an anti-scaling additive)-on microbial community structure and function. Microcosms were constructed with sediment collected upstream (background) or downstream (impacted) from the UIC facility in West Virginia. Exposure to elevated TDS resulted in a significant decrease in aerobic respiration, and microbial community analysis following incubation indicated that elevated TDS could be linked to the majority of change in community structure. Over the course of the incubation, the sediment layer in the microcosms became anoxic, and addition of DBNPA was observed to inhibit iron reduction. In general, disruptions to microbial community structure and function were more pronounced in upstream and background sediment microcosms than in impacted sediment microcosms. These results suggest that the microbial community in impacted sediments had adapted following exposure to OG wastewater releases from the site. Our findings demonstrate the potential for releases from an OG wastewater disposal facility to alter microbial communities and biogeochemical processes. We anticipate that these studies will aid in the development of useful models for the potential impact of UIC disposal facilities on adjoining surface water and shallow groundwater., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Any use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the U.S. Government. The authors declare no competing financial interest., (Copyright © 2021 Akob, Mumford, Fraser, Harris, Orem, Varonka and Cozzarelli.)

The genetic causes of ileal neuroendocrine tumors (ileal NETs, or I-NETs) have been a mystery. For most types of tumors, key genes were revealed by large scale genomic sequencing that demonstrated recurrent mutations of specific oncogenes or tumor suppressors. In contrast, genomic sequencing of ileal NETs demonstrated a distinct lack of recurrently mutated genes, suggesting that the mechanisms that drive the formation of I-NETs may be quite different than the cell-intrinsic mutations that drive the formation of other tumor types. However, recent mouse studies have identified the IGF2 and RB1 pathways in the formation of ileal NETs, which is supported by the subsequent analysis of patient samples. Thus, ileal NETs no longer appear to be a cancer without genetic causes.

Introduction: The SARS-CoV-2 (COVID-19) pandemic has exposed health disparities throughout the USA, particularly among racial and ethnic minorities. As a result, there is a need for data-driven approaches to pinpoint the unique constellation of clinical and social determinants of health (SDOH) risk factors that give rise to poor patient outcomes following infection in US communities., Methods: We combined county-level COVID-19 testing data, COVID-19 vaccination rates and SDOH information in Tennessee. Between February and May 2021, we trained machine learning models on a semimonthly basis using these datasets to predict COVID-19 incidence in Tennessee counties. We then analyzed SDOH data features at each time point to rank the impact of each feature on model performance., Results: Our results indicate that COVID-19 vaccination rates play a crucial role in determining future COVID-19 disease risk. Beginning in mid-March 2021, higher vaccination rates significantly correlated with lower COVID-19 case growth predictions. Further, as the relative importance of COVID-19 vaccination data features grew, demographic SDOH features such as age, race and ethnicity decreased while the impact of socioeconomic and environmental factors, including access to healthcare and transportation, increased., Conclusion: Incorporating a data framework to track the evolving patterns of community-level SDOH risk factors could provide policy-makers with additional data resources to improve health equity and resilience to future public health emergencies., Competing Interests: Competing interests: LSW, JDG and CFS are shareholders in IQuity Labs (Nashville, Tennessee, USA) and Decode Health (Nashville, Tennessee, USA). IQuity Labs develops blood-based RNA tools to aid in the diagnosis and treatment of human disease. Decode Health develops artificial intelligence approaches to predict chronic and infectious disease risk in patient populations., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The SARS-CoV-2 (COVID-19) pandemic has exposed the need to understand the risk drivers that contribute to uneven morbidity and mortality in US communities. Addressing the community-specific social determinants of health (SDOH) that correlate with spread of SARS-CoV-2 provides an opportunity for targeted public health intervention to promote greater resilience to viral respiratory infections., Methods: Our work combined publicly available COVID-19 statistics with county-level SDOH information. Machine learning models were trained to predict COVID-19 case growth and understand the social, physical and environmental risk factors associated with higher rates of SARS-CoV-2 infection in Tennessee and Georgia counties. Model accuracy was assessed comparing predicted case counts to actual positive case counts in each county., Results: The predictive models achieved a mean R 2 of 0.998 in both states with accuracy above 90% for all time points examined. Using these models, we tracked the importance of SDOH data features over time to uncover the specific racial demographic characteristics strongly associated with COVID-19 incidence in Tennessee and Georgia counties. Our results point to dynamic racial trends in both states over time and varying, localized patterns of risk among counties within the same state. For example, we find that African American and Asian racial demographics present comparable, and contrasting, patterns of risk depending on locality., Conclusion: The dichotomy of demographic trends presented here emphasizes the importance of understanding the unique factors that influence COVID-19 incidence. Identifying these specific risk factors tied to COVID-19 case growth can help stakeholders target regional interventions to mitigate the burden of future outbreaks., Competing Interests: Competing interests: JDG, LSW and CFS are shareholders in IQuity Labs, Inc. (Nashville, Tennessee) and Decode Health, Inc. (Nashville, Tennessee). IQuity Labs, Inc. develops blood-based RNA tools to aid in the diagnosis and treatment of human disease. Decode Health, Inc. develops artificial intelligence approaches to predict chronic and infectious disease risk in patient populations., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Objective: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are standard treatments for intermediate-size (15-20 mm) kidney stones but differ in their postoperative recovery, stone-free rates, and complication risks. We aimed to evaluate what affects patient treatment preferences. Methods: Patients with urinary stone disease completed a choice-based conjoint analysis exercise assessing four treatment attributes associated with URS and PCNL. A sensitivity analysis using a market simulator was performed, and the relative importance of each attribute was calculated. Differences in treatment preferences by demographic subgroup were assessed. Results: A total of 58 patients completed the conjoint analysis exercise. Stone-free rate was the most important treatment attribute, while the length of hospital stay and cosmesis were less important. Overall, sensitivity analysis based on market simulation scenarios predicted an almost equal preference for URS (52.4%) compared with PCNL (47.6%) for treatment of an intermediate-size stone. Older patients (>65 years old) expressed their stronger preferences for lower infection rates and shorter hospital stays, and were more likely to prefer URS (67.2%, 95% confidence interval [CI]: 52% to 82.5%) compared with younger patients (20-34 years old) (20.3%, 95% CI: 0% to 41.5%) who preferred higher procedure success rates and fewer repeat procedures. Conclusion: Conjoint analysis predicts nearly equal patient preference for URS or PCNL for the treatment of intermediate-size kidney stones. Older patients prefer the lower urinary tract infection risk and shorter hospital stay associated with URS, while younger patients prefer higher stone-free rates associated with PCNL. These results can help guide urologists in counseling patients and improve the shared decision-making process.

Here, we present the draft genome sequence of Bordetella sp. strain FB-8, a mixotrophic iron-oxidizing bacterium isolated from creek sediment in the former uranium-mining district of Ronneburg, Germany. To date, iron oxidation has not been reported in Bordetella species, indicating that FB-8 may be an environmentally important Bordetella sp.

Objectives: To examine opinions on trainee independence and attending presence among a cross-section of the general population and explore how perceptions of trust, past experiences, and demographics interacted with comfort consenting to these surgical scenarios., Study Design: Mixed-methods METHODS: Based on prior qualitative analysis, we designed a survey of patient preferences and values that focused on trust in healthcare practitioners and processes, which also included comfort ratings of three surgical scenarios (including overlapping surgery). The survey was administered to a sample from the general public using Mechanical Turk. We identified discreet domains of trust and examined the association of responses to these domains with comfort ratings, prior healthcare experiences, and demographics., Results: We analyzed 225 surveys and identified four patient subgroups based on responses to the surgical scenarios. Subjects that were more comfortable with overlapping surgery were more trusting of trainees and delegation by the attending. Past experiences in healthcare (positive and negative) were associated with multiple domains of trust (in trainees, surgeons, and the healthcare system). Demographics were not predictive of trust responses or comfort ratings., Conclusion: Patients express varying degrees of comfort with overlapping surgery, and this is not associated with demographics. Past negative experiences have an impact on trust in the healthcare system overall, and trust in trainees specifically predicts comfort with attending absence from the operating room. Efforts to increase patient comfort with overlapping surgery and surgical training should include strategies to address past negative experiences and foster trust in trainees and the delegation process., Level of Evidence: IV Laryngoscope, 130:2728-2735, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science, engineering, finance and economics. For example, in astronomy, NumPy was an important part of the software stack used in the discovery of gravitational waves 1 and in the first imaging of a black hole 2 . Here we review how a few fundamental array concepts lead to a simple and powerful programming paradigm for organizing, exploring and analysing scientific data. NumPy is the foundation upon which the scientific Python ecosystem is constructed. It is so pervasive that several projects, targeting audiences with specialized needs, have developed their own NumPy-like interfaces and array objects. Owing to its central position in the ecosystem, NumPy increasingly acts as an interoperability layer between such array computation libraries and, together with its application programming interface (API), provides a flexible framework to support the next decade of scientific and industrial analysis.

Ileal neuroendocrine tumors (I-NETs) are the most common tumors of the small intestine. Although I-NETs are known for a lack of recurrently mutated genes, a majority of tumors do show loss of one copy of chromosome 18. Among the genes on chromosome 18 is MIR1-2, which encodes a microRNA, MIR1-3p, with high complementarity to the mRNA of CDK4. Here we show that transfection of neuroendocrine cell lines with MIR1-3p lowered CDK4 expression and activity, and arrested growth at the G1 stage of the cell cycle. Loss of copy of MIR1-2 in ileal neuroendocrine tumors associated with increased expression of CDK4. Genetic events that attenuated RB activity, including loss of copy of MIR1-2 as well as loss of copy of CDKN1B and CDKN2A, were more frequent in tumors from patients with metastatic I-NETs. These data suggest that inhibitors of CDK4/CDK6 may benefit patients whose I-NETs show loss of copy of MIR1-2, particularly patients with metastatic disease.

The perceived replication crisis and the reforms designed to address it are grounded in the notion that science is a binary signal detection problem. However, contrary to null hypothesis significance testing (NHST) logic, the magnitude of the underlying effect size for a given experiment is best conceptualized as a random draw from a continuous distribution, not as a random draw from a dichotomous distribution (null vs. alternative). Moreover, because continuously distributed effects selected using a P < 0.05 filter must be inflated, the fact that they are smaller when replicated (reflecting regression to the mean) is no reason to sound the alarm. Considered from this perspective, recent replication efforts suggest that most published P < 0.05 scientific findings are "true" (i.e., in the correct direction), with observed effect sizes that are inflated to varying degrees. We propose that original science is a screening process, one that adopts NHST logic as a useful fiction for selecting true effects that are potentially large enough to be of interest to other scientists. Unlike original science, replication science seeks to precisely measure the underlying effect size associated with an experimental protocol via large- N direct replication, without regard for statistical significance. Registered reports are well suited to (often resource-intensive) direct replications, which should focus on influential findings and be published regardless of outcome. Conceptual replications play an important but separate role in validating theories. However, because they are part of NHST-based original science, conceptual replications cannot serve as the field's self-correction mechanism. Only direct replications can do that., Competing Interests: The authors declare no competing interest.

By the strictest of definitions, a genetic driver of tumorigenesis should fulfill two criteria: it should be altered in a high percentage of patient tumors, and it should also be able to cause the same type of tumor to form in mice. No gene that fits either of these criteria has ever been found for ileal neuroendocrine tumors (I-NETs), which in humans are known for an unusual lack of recurrently mutated genes, and which have never been detected in mice. In the following report, we show that I-NETs can be generated by transgenic RT2 mice, which is a classic model for a genetically unrelated disease, pancreatic neuroendocrine tumors (PNETs). The ability of RT2 mice to generate I-NETs depended upon genetic background. I-NETs appeared in a B6AF1 genetic background, but not in a B6 background nor even in an AB6F1 background. AB6F1 and B6AF1 have identical nuclear DNA but can potentially express different allelic forms of imprinted genes. This led us to test human I-NETs for loss of imprinting, and we discovered that the IGF2 gene showed loss of imprinting and increased expression in the I-NETs of 57% of patients. By increasing IGF2 activity genetically, I-NETs could be produced by RT2 mice in a B6 genetic background, which otherwise never developed I-NETs. The facts that IGF2 is altered in a high percentage of patients with I-NETs and that I-NETs can form in mice that have elevated IGF2 activity, define IGF2 as the first genetic driver of ileal neuroendocrine tumorigenesis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments.