The Cell Tracking Challenge: 10 years of objective benchmarking.

The Cell Tracking Challenge is an ongoing benchmarking initiative that has become a reference in cell segmentation and tracking algorithm development. Here, we present a significant number of improvements introduced in the challenge since our 2017 report. These include the creation of a new segmentation-only benchmark, the enrichment of the dataset repository with new datasets that increase its diversity and complexity, and the creation of a silver standard reference corpus based on the most competitive results, which will be of particular interest for data-hungry deep learning-based strategies. Furthermore, we present the up-to-date cell segmentation and tracking leaderboards, an in-depth analysis of the relationship between the performance of the state-of-the-art methods and the properties of the datasets and annotations, and two novel, insightful studies about the generalizability and the reusability of top-performing methods. These studies provide critical practical conclusions for both developers and users of traditional and machine learning-based cell segmentation and tracking algorithms.

Plio-Pleistocene environmental variability in Africa and its implications for mammalian evolution.

Understanding the climatic drivers of environmental variability (EV) during the Plio-Pleistocene and EV's influence on mammalian macroevolution are two outstanding foci of research in African paleoclimatology and evolutionary biology. The potential effects of EV are especially relevant for testing the variability selection hypothesis, which predicts a positive relationship between EV and speciation and extinction rates in fossil mammals. Addressing these questions is stymied, however, by 1) a lack of multiple comparable EV records of sufficient temporal resolution and duration, and 2) the incompleteness of the mammalian fossil record. Here, we first compile a composite history of Pan-African EV spanning the Plio-Pleistocene, which allows us to explore which climatic variables influenced EV. We find that EV exhibits 1) a long-term trend of increasing variability since ∼3.7 Ma, coincident with rising variability in global ice volume and sea surface temperatures around Africa, and 2) a 400-ky frequency correlated with seasonal insolation variability. We then estimate speciation and extinction rates for fossil mammals from eastern Africa using a method that accounts for sampling variation. We find no statistically significant relationship between EV and estimated speciation or extinction rates across multiple spatial scales. These findings are inconsistent with the variability selection hypothesis as applied to macroevolutionary processes.

Personal genital satisfaction is associated with differences in perception of male and female sexual anatomy and function.

BACKGROUND: Prior studies primarily of men correlated low personal genital satisfaction (PGS) with decreased sexual activity; however, the association between PGS and genital anatomy perceptions is unknown, and there is a paucity of studies examining women. AIM: We assessed the relationship between genital satisfaction, survey respondent sexual activity, and perceptions of anatomy and function. METHODS: A 54-item REDCap survey was distributed to any-gendered volunteers ≥18 years of age through ResearchMatch from January to March 2023. Responses were split into (1) high PGS and (2) low PGS. Analysis was performed using chi-square tests on survey responses and a Mann Whitney U test on median satisfaction level. OUTCOMES: Outcomes were genital anatomy perceptions, sexual activity, and respondents' PGS. RESULTS: Of the 649 respondents who started the survey, 560 (86.3%) completed it. Median PGS was 7 of 10, forming subgroups of high (≥7 of 10) satisfaction (n = 317 of 560 [56.6%]) and low (<7 of 10) satisfaction (n = 243 of 560 [43.4%]). The mean age was 45.8 ± 16.8 years, and demographics were notable for 72.1% women (n = 404 of 560), 83.2% White (n = 466 of 560), 47.9% married (n = 268 of 560), and 75.5% bachelor's degree holders (n = 423 of 560). Comparing high- and low-PGS groups, more low-PGS respondents felt normal flaccid penis length to be <2 inches (11.1% vs 5.1%; P = .008). High-PGS respondents more often responded that it is normal for women to have orgasms over half the time (20.8% vs 13.2%; P = .0002) or to identify as being sexually active (81.1% vs 71.6%; P = .008). Women were more likely than men to report larger normal testicle sizes as 60.1 to 90 mL (24.5% vs 10.3%; P < .0001), whereas more men felt that normal testicle size was 7 to 15 mL (26.3% vs 11.4%; P < .0001). Orgasm length perceptions also differed: more women felt female orgasm length was 2.6 to 5 seconds (36.6% vs 16.7%; P < .0001), and more men believed female orgasms to be longer, at 7.6 to 10 seconds (29.5% vs 17.3%; P = .002), 10.1 to 12.5 seconds (11.5% vs 5.2%; P = .0008), and >12.5 seconds (12.2% vs 5.7%; P = .009). Respondents' views on their genitalia differed by gender, with women more likely to feel that their genitals are normal compared with men (89.4% vs 75.0%; P < .0001). CLINICAL IMPLICATIONS: PGS may be a useful screening tool given its association with sexual activity. STRENGTHS AND LIMITATIONS: Our large-scale survey assesses public perceptions of genital anatomy and function. Limitations include a lack of gender nonbinary perceptions. CONCLUSION: Gender and PGS interact with perceptions of male anatomy and female sexual activity, and the frequency of sexual activity was higher among high-PGS respondents; however, the direction of these interactions remains unclear and requires future causal analysis.

Testing alternative hypotheses for the decline of cichlid fish in Lake Victoria using fish tooth time series from sediment cores.

Lake Victoria is well known for its high diversity of endemic fish species and provides livelihoods for millions of people. The lake garnered widespread attention during the twentieth century as major environmental and ecological changes modified the fish community with the extinction of approximately 40% of endemic cichlid species by the 1980s. Suggested causal factors include anthropogenic eutrophication, fishing, and introduced non-native species but their relative importance remains unresolved, partly because monitoring data started in the 1970s when changes were already underway. Here, for the first time, we reconstruct two time series, covering the last approximately 200 years, of fish assemblage using fish teeth preserved in lake sediments. Two sediment cores from the Mwanza Gulf of Lake Victoria, were subsampled continuously at an intra-decadal resolution, and teeth were identified to major taxa: Cyprinoidea, Haplochromini, Mochokidae and Oreochromini. None of the fossils could be confidently assigned to non-native Nile perch. Our data show significant decreases in haplochromine and oreochromine cichlid fish abundances that began long before the arrival of Nile perch. Cyprinoids, on the other hand, have generally been increasing. Our study is the first to reconstruct a time series of any fish assemblage in Lake Victoria extending deeper back in time than the past 50 years, helping shed light on the processes underlying Lake Victoria's biodiversity loss.

Paleo-ENSO influence on African environments and early modern humans.

In this study, we synthesize terrestrial and marine proxy records, spanning the past 620 ky, to decipher pan-African climate variability and its drivers and potential linkages to hominin evolution. We find a tight correlation between moisture availability across Africa to El Niño Southern Ocean oscillation (ENSO) variability, a manifestation of the Walker Circulation, that was most likely driven by changes in Earth's eccentricity. Our results demonstrate that low-latitude insolation was a prominent driver of pan-African climate change during the Middle to Late Pleistocene. We argue that these low-latitude climate processes governed the dispersion and evolution of vegetation as well as mammals in eastern and western Africa by increasing resource-rich and stable ecotonal settings thought to have been important to early modern humans.

Retrospective Multicenter Observational Study of Immediate Voiding at End of Urinary Sphincter Surgery (REMOVE).

PURPOSE: Patients may remain catheterized after artificial urinary sphincter surgery to prevent urinary retention, despite a lack of evidence to support this practice. Our study aims to evaluate the feasibility of outpatient, catheter-free continence surgery using a multi-institutional database. We hypothesize that between catheterized controls and patients without a catheter, there would be no difference in the rate of urinary retention or postoperative complications. MATERIALS AND METHODS: We conducted a retrospective review of patients undergoing first-time artificial urinary sphincter placement from 2009-2021. Patients were stratified by postoperative catheter status into either no-catheter (leaving the procedure without a catheter) or catheter (postoperative indwelling catheter for ∼24 hours). The primary outcome, urinary retention, was defined as catheterization due to subjective voiding difficulty or documented postvoid residual over 250 mL. RESULTS: Our study identified 302 catheter and 123 no-catheter patients. Twenty (6.6%) catheter and 9 (7.3%) no-catheter patients developed urinary retention (P = .8). On multivariable analysis, controlling for age, cuff size, radiation history and surgeon, there was no statistically significant association between omitting a catheter and urinary retention (OR: 0.45, 95% CI: 0.13-1.58; P = .2). Furthermore, at 30 months follow-up, Kaplan-Meier survival analysis revealed that device survival was 70% (95% CI: 62%-76%) vs 69% (95% CI: 48%-82%) for the catheter and no-catheter group, respectively. CONCLUSIONS: In our multi-institutional cohort, overall retention rates were low (7%) in groups with a catheter and without. Obviating postoperative catheterization facilitates outpatient incontinence surgery without altering reoperation over medium-term follow-up.

Atlantoaxial instability associated with ALDH18A1 mutation.

We report a 10-year-old boy with a de novo pathogenic variant in ALDH18A1, a rare form of metabolic cutis laxa, which was complicated by atlantoaxial instability and spinal cord compression following a fall from standing height. The patient required emergent cervical spine fusion and decompression followed by a 2-month hospitalization and rehabilitation. In addition to the core clinical features of joint and skin laxity, hypotonia, and developmental delays, we expand the connective tissue phenotype by adding a new potential feature of cervical spine instability. Patients with pathogenic variants in ALDH18A1 may warrant cervical spine screening to minimize possible morbidity. Neurosurgeons, geneticists, primary care providers, and families should be aware of the increased risk of severe cervical injury from minor trauma.

Navigating the COVID-19 pandemic together: Discussions between persons with early-stage dementia and their adult children.

OBJECTIVES: Studies have separately examined the health impacts of the COVID-19 pandemic on persons with dementia and their caregivers. Less attention has been paid to the social and emotional impacts of the pandemic in this population or how these individuals are mutually coping with the pandemic. Guided by the social citizenship theory, this qualitative study sought to characterize how persons with dementia and their adult children are coping during this time with a focus on the strengths demonstrated by persons with dementia. METHODS: Participants were 43 dyads of individuals aged 55 and older with early-stage dementia and their adult children. Discussions between parent-child dyads were recorded. Using reflexive thematic analysis, themes related to social and emotional impacts of the pandemic and coping strategies were identified. RESULTS: Adult children shared with their parents how the pandemic resulted in reduced social engagement and challenging work arrangements. Dyads described how the pandemic positively impacted their relationship, allowing some of them to spend more time together. In coping with the pandemic, adult children provided instrumental support to their parents and parents reciprocated with emotional support. Participants also coped by making meaning of their situation during discussions. CONCLUSIONS: Findings characterize the resilience of persons with dementia and the mutuality of the relationship between both members of the care partner dyad, as both parents and adult children offered support to one another. Facilitating dyadic discussions may be a cost-effective way to sustain social connections and offer ongoing coping support through the pandemic or other challenging circumstances.

Applying systems-level spectral imaging and analysis to reveal the organelle interactome.

The organization of the eukaryotic cell into discrete membrane-bound organelles allows for the separation of incompatible biochemical processes, but the activities of these organelles must be coordinated. For example, lipid metabolism is distributed between the endoplasmic reticulum for lipid synthesis, lipid droplets for storage and transport, mitochondria and peroxisomes for ß-oxidation, and lysosomes for lipid hydrolysis and recycling. It is increasingly recognized that organelle contacts have a vital role in diverse cellular functions. However, the spatial and temporal organization of organelles within the cell remains poorly characterized, as fluorescence imaging approaches are limited in the number of different labels that can be distinguished in a single image. Here we present a systems-level analysis of the organelle interactome using a multispectral image acquisition method that overcomes the challenge of spectral overlap in the fluorescent protein palette. We used confocal and lattice light sheet instrumentation and an imaging informatics pipeline of five steps to achieve mapping of organelle numbers, volumes, speeds, positions and dynamic inter-organelle contacts in live cells from a monkey fibroblast cell line. We describe the frequency and locality of two-, three-, four- and five-way interactions among six different membrane-bound organelles (endoplasmic reticulum, Golgi, lysosome, peroxisome, mitochondria and lipid droplet) and show how these relationships change over time. We demonstrate that each organelle has a characteristic distribution and dispersion pattern in three-dimensional space and that there is a reproducible pattern of contacts among the six organelles, that is affected by microtubule and cell nutrient status. These live-cell confocal and lattice light sheet spectral imaging approaches are applicable to any cell system expressing multiple fluorescent probes, whether in normal conditions or when cells are exposed to disturbances such as drugs, pathogens or stress. This methodology thus offers a powerful descriptive tool and can be used to develop hypotheses about cellular organization and dynamics.

Conservative management of scrotal pyoceles - A case series and literature review.

STUDY OBJECTIVE: We describe the common presenting signs and symptoms, treatment modalities, and outcomes of acutely presenting scrotal pyoceles. METHODS: We conducted a retrospective chart review of all adult patients treated for ultrasound-confirmed scrotal pyoceles between 2010 and 2020 at two sites within the [redacted]. Vitals at presentation, microbiology, and inpatient courses including antibiotic treatment and surgical procedures were collected. RESULTS: A total of 360 scrotal ultrasounds were reviewed identifying 15 patients with pyoceles, 11 patients presenting to the emergency department and 4 hospitalized patients. The most common chief complaint was testicular pain (67%). Only seven patients (47%) met SIRS criteria upon presentation. All patients were initially treated with broad-spectrum antibiotics and observation; 11 (73%) responded to this management alone, while four patients (27%) required surgical drainage due to persistent infection. No patients contracted Fournier's gangrene. CONCLUSION: This study reports the largest published database of scrotal pyoceles to date and describes our clinical approach to management. While pyoceles have traditionally been treated aggressively with surgical drainage, this case series suggests that most patients improve with broad-spectrum antibiotic treatment and observation alone, requiring surgical drainage if infection persists. Future investigations including multi-institutional data will be necessary to validate our institution's approach.

African climate response to orbital and glacial forcing in 140,000-y simulation with implications for early modern human environments.

A climate/vegetation model simulates episodic wetter and drier periods at the 21,000-y precession period in eastern North Africa, the Arabian Peninsula, and the Levant over the past 140,000 y. Large orbitally forced wet/dry extremes occur during interglacial time, ∼130 to 80 ka, and conditions between these two extremes prevail during glacial time, ∼70 to 15 ka. Orbital precession causes high seasonality in Northern Hemisphere (NH) insolation at ∼125, 105, and 83 ka, with stronger and northward extended summer monsoon rains in North Africa and the Arabian Peninsula and increased winter rains in the Mediterranean Basin. The combined effects of these two seasonally distinct rainfall regimes increase vegetation and narrow the width of the Saharan-Arabian desert and semidesert zones. During the opposite phase of the precession cycle (∼115, 95, and 73 ka), NH seasonality is low, and decreased summer insolation and increased winter insolation cause monsoon and storm track rains to decrease and the width of the desert zone to increase. During glacial time (∼70 to 15 ka), forcing from large ice sheets and lowered greenhouse gas concentrations combine to increase winter Mediterranean storm track precipitation; the southward retreat of the northern limit of summer monsoon rains is relatively small, thereby limiting the expansion of deserts. The lowered greenhouse gas concentrations cause the near-equatorial zone to cool and reduce convection, causing drier climate with reduced forest cover. At most locations and times, the simulations agree with environmental observations. These changing regional patterns of climate/vegetation could have influenced the dispersal of early humans through expansions and contractions of well-watered corridors.

Guardianship Before and Following Hospitalization.

When ethics committees are consulted about patients who have or need court-appointed guardians, they lack empirical evidence about several common issues, including the relationship between guardianship and prolonged, potentially medically unnecessary hospitalizations for patients. To provide information about this issue, we conducted quantitative and qualitative analyses using a retrospective cohort from Veterans Healthcare Administration. To examine the relationship between guardianship appointment and hospital length of stay, we first compared 116 persons hospitalized prior to guardianship appointment to a comparison group (n = 348) 3:1 matched for age, diagnosis, date of admission, and comorbidity. We then compared 91 persons hospitalized in the year following guardianship appointment to a second matched comparison group (n = 273). Mean length of stay was 30.75 days (SD = 46.70) amongst those admitted prior to guardianship, which was higher than the comparison group (M = 7.74, SD = 9.71, F = 20.75, p < .001). Length of stay was lower following guardianship appointment (11.65, SD = 12.02, t = 15.16, p < .001); while higher than the comparison group (M = 7.60, SD = 8.46), differences were not associated with guardianship status. In a separate analysis involving 35 individuals who were hospitalized both prior to and following guardianship, length of stay was longer in the year prior (M = 23.00, SD = 37.55) versus after guardianship (M = 10.37, SD = 10.89, F = 4.35, p = .045). In qualitative analyses, four themes associated with lengths of stay exceeding 45 days prior to guardianship appointment were: administrative issues, family conflict, neuropsychiatric comorbidity, and medical complications. Our results suggest that persons who are admitted to hospitals, and subsequently require a guardian, experience extended lengths of stay for multiple complex reasons. Once a guardian has been appointed, however, differences in hospital lengths of stay between patients with and without guardians are reduced.

Association between Previous Pelvic Radiation and All-Cause and Cause-Specific Failure of Replacement Artificial Urinary Sphincters.

PURPOSE: In order to accurately characterize how a history of radiation therapy affects the lifespan of replacement artificial urinary sphincters (AUSs), all possible sources of device failure must be considered. We assessed the competing risks of device failure based on radiation history in men with replacement AUSs. MATERIALS AND METHODS: We identified men who had a replacement AUS in a single institutional, retrospective database. To assess survival from all-cause device failure based on radiation history and other factors, we conducted Kaplan-Meier, Cox proportional-hazards and competing risks analyses. RESULTS: Among 247 men who had a first replacement AUS, men with a history of radiation had shorter time to all-cause device failure (median 1.4 vs 3.5 years for men with radiation vs without radiation history, p=0.02). On multivariable Cox-proportional hazards analysis, previous radiation was associated with increased risk of all-cause device failure (HR: 2.12, 95% CI: 1.30-3.43, p=0.002). On multivariable cause-specific hazards analysis, prior radiation was associated with a higher risk of erosion/infection (HR: 7.57, 95% CI: 2.27-25.2, p <0.001), but was not associated with risk of urethral atrophy (p=0.5) or mechanical failure (p=0.15). CONCLUSIONS: Among men with a replacement AUS, a history of pelvic radiation was associated with shorter time to device failure of any cause. Radiation was also specifically associated with a sevenfold increase in the risk of erosion or infection of replacement AUS, but not with urethral atrophy or mechanical failure. Patients with a replacement AUS should be appropriately counseled on how radiation history may impact outcomes of future revisions.

Calcium-vesicles perform active diffusion in the sea urchin embryo during larval biomineralization.

Biomineralization is the process by which organisms use minerals to harden their tissues and provide them with physical support. Biomineralizing cells concentrate the mineral in vesicles that they secret into a dedicated compartment where crystallization occurs. The dynamics of vesicle motion and the molecular mechanisms that control it, are not well understood. Sea urchin larval skeletogenesis provides an excellent platform for investigating the kinetics of mineral-bearing vesicles. Here we used lattice light-sheet microscopy to study the three-dimensional (3D) dynamics of calcium-bearing vesicles in the cells of normal sea urchin embryos and of embryos where skeletogenesis is blocked through the inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR). We developed computational tools for displaying 3D-volumetric movies and for automatically quantifying vesicle dynamics. Our findings imply that calcium vesicles perform an active diffusion motion in both, calcifying (skeletogenic) and non-calcifying (ectodermal) cells of the embryo. The diffusion coefficient and vesicle speed are larger in the mesenchymal skeletogenic cells compared to the epithelial ectodermal cells. These differences are possibly due to the distinct mechanical properties of the two tissues, demonstrated by the enhanced f-actin accumulation and myosinII activity in the ectodermal cells compared to the skeletogenic cells. Vesicle motion is not directed toward the biomineralization compartment, but the vesicles slow down when they approach it, and probably bind for mineral deposition. VEGFR inhibition leads to an increase of vesicle volume but hardly changes vesicle kinetics and doesn't affect f-actin accumulation and myosinII activity. Thus, calcium vesicles perform an active diffusion motion in the cells of the sea urchin embryo, with diffusion length and speed that inversely correlate with the strength of the actomyosin network. Overall, our studies provide an unprecedented view of calcium vesicle 3D-dynamics and point toward cytoskeleton remodeling as an important effector of the motion of mineral-bearing vesicles.

Lead Foot Progression Angle in Baseball Pitchers: Implications to Ball Velocity and Upper-Extremity Joint Moments.

The instant of foot contact is an important transition point during the pitch cycle between the linear portion of the pitch, as a pitcher strides down the mound and the rotational portion of the pitch. Understanding the implications of lead foot angle at foot contact is an essential information needed to assist pitching coaches in their work with individual pitchers. Therefore, the purpose of this study was to determine the association between lead foot progression angle at foot contact and ball velocity, elbow varus moment, and pelvic rotation. Kinematic and kinetic data were collected from 99 collegiate pitchers and analyzed using a random intercept, mixed-effects regression model. Significant associations were found between lead foot progression angle at foot contact and elbow varus moment (P = .004), as well as pelvic rotation throughout the pitching motion (P < .001). The data indicate that increased lead foot internal rotation at foot contact is associated with increases in the elbow varus moment but is not associated with ball velocity. This study provides scientific evidence that the rotational positioning of the lead foot can affect both pelvic motion and upper-extremity joint moments.

Contemporary Trends and End-Results of National Institutes of Health Grant Funding to Departments of Urology in the United States: A 10-year Analysis.

PURPOSE: We explored the patterns and distribution of National Institutes of Health grant funding for urological research in the United States. MATERIALS AND METHODS: The National Institutes of Health RePORTER database was queried for all grants awarded to urology departments between 2010 and 2019. Information regarding the value of the grant, funded institution, successful publication of the research, and the category of urological subspecialty were collected. Data on principal investigators were extracted from publicly available information. RESULTS: There were 509 grants awarded to Urology between 2010 and 2019 for a total value of $640,873,867, and a median per-project value of $675,484 (IQR 344,170-1,369,385). Over the study period, total funding decreased by 15.6% and was lower compared to other surgical subspecialties. Most grants were awarded by the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases (85%) to Western or North Central institutions (52.5%), and had principal investigators specialized in urologic oncology (56.4%), followed by general urologists (21.5%). Female principal investigators led 21.6% of Urology grants and were more likely PhD basic scientists than males (64.4% vs 38.2%, p=0.001). In total, 10,404 publications linked to the 509 grants were produced, of which 28.5% were published in journals with an impact factor ≥10. CONCLUSIONS: Urology is underrepresented in National Institutes of Health grant funding compared to other surgical fields. During the past decade there was a further decrease in the total budget of National Institutes of Health grants to Urology.

Demographic Characteristics Driving Disparities in Receipt of Long-term Services and Supports in the Community Setting.

BACKGROUND: Research suggests that growth in Black and Hispanic (minority) older adults' nursing home (NH) use may be the result of disparities in access to community-based and alternative long-term services and supports (LTSS). OBJECTIVE: We aimed to determine whether minority groups receiving care in NHs versus the community had fewer differences in their functional needs compared with the differences in nonminority older adults, suggesting a disparity. METHODS: We identified respondents aged 65 years or above with a diagnosis of Alzheimer disease or dementia in the 2016 Health and Retirement Study who reported requiring LTSS help. We performed unadjusted analyses to assess the difference in functional need between community and NH care. Functional need was operationalized using a functional limitations score and 6 individual activities of daily living. We compared the LTSS setting for minority older adults to White older adults using difference-in-differences. RESULTS: There were 186 minority older adults (community=75%, NH=25%) and 357 White older adults (community=50%, NH=50%). Between settings, minority older adults did not differ in education or marital status, but were younger and had greater income in the NH versus the community. The functional limitations score was higher in NHs than in the community for both groups. Functional needs for all 6 activities of daily living for the minority group were greater in NHs compared with the community. CONCLUSION: Functional need for minority older adults differed by setting while demographics varied in unexpected ways. Factors such as familial and financial support are important to consider when implementing programs to keep older adults out of NHs.

Synchronous genitourinary lichen sclerosus signals a distinct urinary microbiome profile in men with urethral stricture disease.

PURPOSE: Alterations in the urinary microbiome have been associated with urological diseases. The microbiome of patients with urethral stricture disease (USD) remains unknown. Our objective is to examine the microbiome of USD with a focus on inflammatory USD caused by lichen sclerosus (LS). METHODS: We collected mid-stream urine samples from men with LS-USD (cases; n = 22) and non-LS USD (controls; n = 76). DNA extraction, PCR amplification of the V4 hypervariable region of the 16S rRNA gene, and sequencing was done on the samples. Operational taxonomic units (OTUs) were defined using a > 97% sequence similarity threshold. Alpha diversity measurements of diversity, including microbiome richness (number of different OTUs) and evenness (distribution of OTUs) were calculated and compared. Microbiome beta diversity (difference between microbial communities) relationships with cases and controls were also assessed. RESULTS: Fifty specimens (13 cases and 37 controls) produced a 16S rRNA amplicon. Mean sample richness was 25.9 vs. 16.8 (p = 0.076) for LS-USD vs. non-LS USD, respectively. LS-USD had a unique profile of bacteria by taxonomic order including Bacillales, Bacteroidales and Pasteurellales enriched urine. The beta variation of observed bacterial communities was best explained by the richness. CONCLUSIONS: Men with LS-USD may have a unique microbiologic richness, specifically inclusive of Bacillales, Bacteroidales and Pasteurellales enriched urine compared to those with non-LS USD. Further work will be required to elucidate the clinical relevance of these variations in the urinary microbiome.

Making Medical Treatment Decisions for Unrepresented Patients in the ICU. An Official American Thoracic Society/American Geriatrics Society Policy Statement.

Background and Rationale: ICU clinicians regularly care for patients who lack capacity, an applicable advance directive, and an available surrogate decision-maker. Although there is no consensus on terminology, we refer to these patients as "unrepresented." There is considerable controversy about how to make treatment decisions for these patients, and there is significant variability in both law and clinical practice.Purpose and Objectives: This multisociety statement provides clinicians and hospital administrators with recommendations for decision-making on behalf of unrepresented patients in the critical care setting.Methods: An interprofessional, multidisciplinary expert committee developed this policy statement by using an iterative consensus process with a diverse working group representing critical care medicine, palliative care, pediatric medicine, nursing, social work, gerontology, geriatrics, patient advocacy, bioethics, philosophy, elder law, and health law.Main Results: The committee designed its policy recommendations to promote five ethical goals: 1) to protect highly vulnerable patients, 2) to demonstrate respect for persons, 3) to provide appropriate medical care, 4) to safeguard against unacceptable discrimination, and 5) to avoid undue influence of competing obligations and conflicting interests. These recommendations also are intended to strike an appropriate balance between excessive and insufficient procedural safeguards. The committee makes the following recommendations: 1) institutions should offer advance care planning to prevent patients at high risk for becoming unrepresented from meeting this definition; 2) institutions should implement strategies to determine whether seemingly unrepresented patients are actually unrepresented, including careful capacity assessments and diligent searches for potential surrogates; 3) institutions should manage decision-making for unrepresented patients using input from a diverse interprofessional, multidisciplinary committee rather than ad hoc by treating clinicians; 4) institutions should use all available information on the patient's preferences and values to guide treatment decisions; 5) institutions should manage decision-making for unrepresented patients using a fair process that comports with procedural due process; 6) institutions should employ this fair process even when state law authorizes procedures with less oversight.Conclusions: This multisociety statement provides guidance for clinicians and hospital administrators on medical decision-making for unrepresented patients in the critical care setting.

Progressive aridification in East Africa over the last half million years and implications for human evolution.

Evidence for Quaternary climate change in East Africa has been derived from outcrops on land and lake cores and from marine dust, leaf wax, and pollen records. These data have previously been used to evaluate the impact of climate change on hominin evolution, but correlations have proved to be difficult, given poor data continuity and the great distances between marine cores and terrestrial basins where fossil evidence is located. Here, we present continental coring evidence for progressive aridification since about 575 thousand years before present (ka), based on Lake Magadi (Kenya) sediments. This long-term drying trend was interrupted by many wet-dry cycles, with the greatest variability developing during times of high eccentricity-modulated precession. Intense aridification apparent in the Magadi record took place between 525 and 400 ka, with relatively persistent arid conditions after 350 ka and through to the present. Arid conditions in the Magadi Basin coincide with the Mid-Brunhes Event and overlap with mammalian extinctions in the South Kenya Rift between 500 and 400 ka. The 525 to 400 ka arid phase developed in the South Kenya Rift between the period when the last Acheulean tools are reported (at about 500 ka) and before the appearance of Middle Stone Age artifacts (by about 320 ka). Our data suggest that increasing Middle- to Late-Pleistocene aridification and environmental variability may have been drivers in the physical and cultural evolution of Homo sapiens in East Africa.