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Prostate cancer is a common cancer among males in the US, but little is known about its risk factors, including trace elements. The primary aim of this study was to examine prostate cancer and its association with arsenic and selenium in toenails. We conducted a small, nested case-control study of men residing in Iowa within the Agricultural Health Study cohort, where we also collected toenail samples to test for arsenic and other trace elements. Toenail samples were sent for neutron activation analysis aimed at long-lived trace elements, including arsenic. Logistic regression was used to estimate odds ratios (ORs) for trace element exposures and prostate cancer. A total of 66 prostate cancer cases and 173 healthy controls returned questionnaires, over 99% of which included toenail samples. An increased risk was seen for the highest levels of arsenic (OR = 3.4 confidence interval (CI) of 1.3–8.6 and OR = 2.2, 95% CI of 0.9–5.6) and the highest level of selenium (2.0, 95% CI of 1.0–4.0). These data also show detectable levels of over 50% for 14 of 22 elements detected in the toenails. The association seen here with arsenic and prostate cancer further supports ecological studies finding an association with community levels of arsenic and prostate cancer incidence and mortality.

Abstract The Mars Sample Return mission intends to retrieve a sealed collection of rocks, regolith, and atmosphere sampled from Jezero Crater, Mars, by the NASA Perseverance rover mission. For all life-related research, it is necessary to evaluate water availability in the samples and on Mars. Within the first Martian year, Perseverance has acquired an estimated total mass of 355 g of rocks and regolith, and 38 μmoles of Martian atmospheric gas. Using in-situ observations acquired by the Perseverance rover, we show that the present-day environmental conditions at Jezero allow for the hydration of sulfates, chlorides, and perchlorates and the occasional formation of frost as well as a diurnal atmospheric-surface water exchange of 0.5–10 g water per m2 (assuming a well-mixed atmosphere). At night, when the temperature drops below 190 K, the surface water activity can exceed 0.5, the lowest limit for cell reproduction. During the day, when the temperature is above the cell replication limit of 245 K, water activity is less than 0.02. The environmental conditions at the surface of Jezero Crater, where these samples were acquired, are incompatible with the cell replication limits currently known on Earth.

Abstract Science has a history of excluding marginalized groups, including people who are lesbian, gay, bisexual, trans, queer, and other marginalized gender and sexual identities (LGBTQ+), and recent calls urge the wildlife sciences to address disparities. Literature on inclusion in the life sciences generally has focused on personal affirmation and has neglected comprehensive discussion of barriers rooted in historical, structural, and sociocultural context. In our literature review, we construct a narrative highlighting the intersections between historic LGBTQ+ exclusion in society and wildlife science due to current policy trends, pressures of cis‐heteronormativity, and survival barriers on LGBTQ+ people in wildlife sciences in the United States. Wildlife scientists must have competency on LGBTQ+ marginalization topics to advance inclusion in our discipline, and this should include comprehension of historic and current legislation and social perceptions. To bolster inclusion efforts, we recommend thoughtful data collection on experiences of LGBTQ+ people within the wildlife sciences. To address root causes of exclusion, institutions and organizations should address disparities in financial support, housing, and physical and mental health resources as part of LGBTQ+ advocacy, in addition to interpersonal efforts.

Little is known about the epidemiology of Merkel cell carcinoma (MCC) and mucosal melanoma (MM). Using the United States (US) National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program data, we compared MCC and MM with cutaneous malignant melanoma (CMM) with respect to incidence rates and prognostic factors to better understand disease etiologies. We describe the proportional incidences of the three cancers along with their survival rates based on 20 years of national data. The incidence rates in 2000–2019 were 203.7 per 1,000,000 people for CMM, 5.9 per 1,000,000 people for MCC and 0.1 per 1,000,000 people for MM. The rates of these cancers increased over time, with the rate of MM tripling between 2000–2009 and 2010–2019. The incidences of these cancers increased with age and rates were highest among non-Hispanic Whites. Fewer MCCs and MMS were diagnosed at the local stage compared with CMM. The cases in the 22 SEER registries in California were not proportional to the 2020 population census but instead were higher than expected for CMM and MCC and lower than expected for MM. Conversely, MM rates were higher than expected in Texas and New York. These analyses highlight similarities in the incidence rates of CMM and MCC—and differences between them and MM rates—by state. Understanding more about MCC and MM is important because of their higher potential for late diagnosis and metastasis, which lead to poor survival.

Our goal is to determine whether our objective 9-point Self-Assessment Skin Tone Palette (SASTP) is correlated with a colorimeter’s assessment of a melanin index, so that Hispanic and Black people can be included in skin cancer research where scales were developed for White populations. Subjects were asked to self-identify their skin tones using the SASTP. This study assessed the criterion validity of the SASTP by measuring a range of skin colors compared to a melanin index reported from a colorimeter for the upper-inner arm (non-sun-exposed skin color), and the outer forearm (sun-exposed). Among 188 non-artificial tanners, 50% were White, 30% were Hispanic or White-Hispanic, and 20% were other racial categories. Meanwhile, 70% were female (30% male) and 81% were age 18–29 (19% age 30+). The mean melanin of the upper-inner arm decreased with lighter skin color and stronger tendency to burn. The SASTP in comparison to melanin index values was correlated for both the upper-inner arm (r = 0.81, p < 0.001) and the outer forearm (r = 0.77, p < 0.001). The SASTP provides a 9-point scale that can be considered as an alternative, less expensive method that is comparable to the objective colorimeter melanin index, which may be useful in studies on skin cancer among White, non-White, and Hispanic peoples.

We quantify the air quality and health impacts of Indian crop residue burning and trace these impacts back to individual burning events by hour and district. We find that small interventions, such as burning one hour earlier in the day, may provide broad public health benefits

Drinking-water quality is a rising concern in the United States (US), emphasizing the need to broadly assess exposures and potential health effects at the point-of-use. Drinking-water exposures to per- and poly-fluoroalkyl substances (PFAS) are a national concern, however, there is limited information on PFAS in residential tapwater at the point-of-use, especially from private-wells. We conducted a national reconnaissance to compare human PFAS exposures in unregulated private-well and regulated public-supply tapwater. Tapwater from 716 locations (269 private-wells; 447 public supply) across the US was collected during 2016–2021 including three locations where temporal sampling was conducted. Concentrations of PFAS were assessed by three laboratories and compared with land-use and potential-source metrics to explore drivers of contamination. The number of individual PFAS observed ranged from 1 to 9 (median: 2) with corresponding cumulative concentrations (sum of detected PFAS) ranging from 0.348 to 346 ng/L. Seventeen PFAS were observed at least once with PFBS, PFHxS and PFOA observed most frequently in approximately 15% of the samples. Across the US, PFAS profiles and estimated median cumulative concentrations were similar among private wells and public-supply tapwater. We estimate that at least one PFAS could be detected in about 45% of US drinking-water samples. These detection probabilities varied spatially with limited temporal variation in concentrations/numbers of PFAS detected. Benchmark screening approaches indicated potential human exposure risk was dominated by PFOA and PFOS, when detected. Potential source and land-use information was related to cumulative PFAS concentrations, and the number of PFAS detected; however, corresponding relations with specific PFAS were limited likely due to low detection frequencies and higher detection limits. Information generated supports the need for further assessments of cumulative health risks of PFAS as a class and in combination with other co-occurring contaminants, particularly in unmonitored private-wells where information is limited or not available.

A complete accounting of nearby objects—from the highest-mass white dwarf progenitors down to low-mass brown dwarfs—is now possible, thanks to an almost complete set of trigonometric parallax determinations from Gaia, ground-based surveys, and Spitzer follow-up. We create a census of objects within a Sun-centered sphere of 20 pc radius and check published literature to decompose each binary or higher-order system into its separate components. The result is a volume-limited census of ∼3600 individual star formation products useful in measuring the initial mass function across the stellar (

Abstract This article explores the deep learning approach towards approximating the effective electrical and thermal conductivities of copper (Cu)-carbon nanotube (CNT) composites with CNTs aligned to the field direction. Convolutional neural networks (CNN) are trained to map the two-dimensional images of stochastic Cu-CNT networks to corresponding conductivities. The CNN model learns to estimate the Cu-CNT composite conductivities for various CNT volume fractions, interfacial electrical resistances, R c = 20 Ω–20 kΩ, and interfacial thermal resistances, R ″ t,c = 10−10–10−7 m2K/W. For training the CNNs, the hyperparameters such as learning rate, minibatch size, and hidden layer neurons are optimized. Without iteratively solving the physical governing equations, the trained CNN model approximates the electrical and thermal conductivities within a second with the coefficient of determination (R 2 ) greater than 98%, which may take longer than 100 min for a convectional numerical simulation. This work demonstrates the potential of the deep learning surrogate model for the complex transport processes in composite materials.

Predictors of genitourinary toxicity after post-prostatectomy radiotherapy remain elusive. A previously defined germline DNA signature (PROSTOX) has shown predictive ability for late grade ≥ 2 GU toxicity after intact prostate stereotactic body radiotherapy. We explore whether PROSTOX would predict toxicity among patients receiving post-prostatectomy SBRT on a phase II clinical trial.

Many demand-response schemes fail because they inconvenience consumers or add unnecessary costs. When participating in a typical demand-response scheme, a consumer may be subjected to invasive control systems, communication systems, or data collection. These demand-response schemes can quickly lose their novelty and may annoy customers by curtailing availability of their appliances, such as electric water heaters or air conditioners. This paper demonstrates a self-organizing demand response scheme that uses power lines as a natural, “free” infrastructure for communication. The approach can shave peak demand substantially with no inconvenience to or attention from the user. Tailored signaling schemes and a custom application of low-data-rate power line communication (PLC) enable loads to reliably self-organize their demand. Field experiments with thermostatically-controlled loads in an actively occupied, 24-floor apartment building demonstrate the advantages of the low-data-rate PLC scheme for energy control.

Through adaptive optics (AO) imaging with the SOUL+LUCI instrument at the Large Binocular Telescope we were able to resolve, for the first time, individual stars in the gas-rich galaxy DDO68 C. This system was already suggested to be interacting with the extremely metal-poor dwarf DDO68, but its nature has remained elusive so far because of the presence of a bright foreground star close to its line of sight that hampers a detailed study of its stellar population and distance. In our study, we turned this interloper star into an opportunity to have a deeper insight on DDO68 C, using it as a guide star for the AO correction. Although the new data do not allow for a direct distance measurement through the red giant branch tip method, the combined analysis of the resolved-star color–magnitude diagram, of archival GALEX far-UV and near-UV photometry, and of H α data provides a self-consistent picture in which DDO68 C is at the same ∼13 Mpc distance as its candidate companion DDO68. These results indicate that DDO68 is a unique case of a low-mass dwarf, less massive than the Magellanic Clouds, interacting with three satellites (DDO68 C and two previously confirmed accreting systems), providing useful constraints on cosmological models and a potential explanation for its anomalous extremely low metallicity.

Background: Bottled water (BW) consumption in the United States and globally has increased amidst heightened concern about environmental contaminant exposures and health risks in drinking water supplies, despite a paucity of directly comparable, environmentally-relevant contaminant exposure data for BW. This study provides insight into exposures and cumulative risks to human health from inorganic/organic/microbial contaminants in BW. Methods: BW from 30 total domestic US (23) and imported (7) sources, including purified tapwater (7) and spring water (23), were analyzed for 3 field parameters, 53 inorganics, 465 organics, 14 microbial metrics, and in vitro estrogen receptor (ER) bioactivity. Health-benchmark-weighted cumulative hazard indices and ratios of organic-contaminant in vitro exposure-activity cutoffs were assessed for detected regulated and unregulated inorganic and organic contaminants. Results: 48 inorganics and 45 organics were detected in sampled BW. No enforceable chemical quality standards were exceeded, but several inorganic and organic contaminants with maximum contaminant level goal(s) (MCLG) of zero (no known safe level of exposure to vulnerable sub-populations) were detected. Among these, arsenic, lead, and uranium were detected in 67 %, 17 %, and 57 % of BW, respectively, almost exclusively in spring-sourced samples not treated by advanced filtration. Organic MCLG exceedances included frequent detections of disinfection byproducts (DBP) in tapwater-sourced BW and sporadic detections of DBP and volatile organic chemicals in BW sourced from tapwater and springs. Precautionary health-based screening levels were exceeded frequently and attributed primarily to DBP in tapwater-sourced BW and co-occurring inorganic and organic contaminants in spring-sourced BW. Conclusion: The results indicate that simultaneous exposures to multiple drinking-water contaminants of potential human-health concern are common in BW. Improved understandings of human exposures based on more environmentally realistic and directly comparable point-of-use exposure characterizations, like this BW study, are essential to public health because drinking water is a biological necessity and, consequently, a high-vulnerability vector for human contaminant exposures.

Abstract Background Evidence from previous studies suggests that women firefighters have greater risk of some adverse reproductive outcomes. The purpose of this study was to investigate whether women firefighters had greater risk of miscarriage compared to non-firefighters and whether there were occupational factors associated with risk of miscarriage among firefighters. Methods We studied pregnancies in the United States fire service using data from the Health and Wellness of Women Firefighters Study (n = 3181). We compared the prevalence of miscarriage among firefighters to published rates among non-firefighters using age-standardized prevalence ratios. We used generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs) between occupational factors (employment (career/volunteer), wildland firefighter status (wildland or wildland-urban-interface/structural), shift schedule, fire/rescue calls at pregnancy start) and risk of miscarriage, adjusted for age at pregnancy, education, gravidity, BMI, and smoking. We evaluated if associations varied by age at pregnancy or employment. Results Among 1074 firefighters and 1864 total pregnancies, 404 pregnancies resulted in miscarriages (22%). Among most recent pregnancies, 138 resulted in miscarriage (13%). Compared to a study of US nurses, firefighters had 2.33 times greater age-standardized prevalence of miscarriage (95% CI 1.96–2.75). Overall, we observed that volunteer firefighters had an increased risk of miscarriage which varied by wildland status (interaction p-value

BackgroundPrior studies have shown poor recruitment and retention of minoritized groups in clinical trials.ObjectiveTo examine several social determinants as predictors of consent to participate and retention as part of a prospective, longitudinal cohort study of children 8–16 with either mild traumatic brain injury (mild TBI) or orthopedic injury (OI).MethodsChildren and families were recruited during acute visits to emergency departments (ED) in two large children's hospitals in the midwestern United States for a prospective, longitudinal cohort study of children 8–16 with either mild TBI or OI.ResultsA total of 588 (mild TBI = 307; OI = 281) eligible children were approached in the ED and 315 (mild TBI = 195; OI = 120) were consented. Children who consented did not differ significantly from those who did not consent in sex or age. Consent rates were higher among Black (60.9%) and multi-racial (76.3%) children than white (45.3%) children. Among the 315 children who consented, 217 returned for a post-acute assessment (mild TBI = 143; OI = 74), a retention rate of 68.9%. Participants who were multi-racial (96.6%) or white (79.8%) were more likely to return for the post-acute visit than those who were Black (54.3%).ConclusionsRacial differences exist in both recruitment and retention of participants in a prospective, longitudinal cohort of children with mild TBI or OI. Further work is needed to understand these differences to ensure equitable participation of minoritized groups in brain injury research.

Summary: Background: The freezing response is a universal response to threat, linked to attentive immobility and action preparation. It is relevant for acute stress coping in animals and humans, and subtle deviations in toddler freezing duration (absence of, or excessively long reactions) have been linked to higher risk for internalizing symptoms in adolescence. Yet, while individual freezing tendencies are relatively stable throughout life, little is known about their gene-environment aetiology. Methods: We investigated the heritability of toddler freezing in the Quebec Newborn Twin Study (QNTS; n=508 twins) by fitting behavioural genetic models to video-coded freezing responses during a robot confrontation. Furthermore, we examined the predictive associations between toddler freezing and internalizing symptoms (anxiety and depressive symptoms), as they unfold during adolescence (ages 12–19 years) using linear mixed-effects models. Findings: Freezing was found to be moderately heritable (45% of the variance accounted for by genetic factors). The remaining variance was explained by unique environmental factors, including measurement error. No significant contribution of shared environmental factors was noted. Additionally, shorter freezing was associated with more internalizing symptoms in adolescence at trend level, a pattern that was significant for depressive but not anxiety symptoms. Interpretation: Freezing is an adaptive coping mechanism in early childhood, which is partly driven by genetic factors. Crucially, the absence or shorter duration of these behaviours may signal vulnerability to depressive problems later in life. Funding: Canadian Institutes of Health Research and Research Fund of Quebec–Health and Society and Culture. Consolidator grant from the European Research Council (ERC_CoG-2017_772337).

ABSTRACT Introduction In surgical series of muscle‐invasive bladder cancer (MIBC), women have higher recurrence rates, disease progression, and mortality following radical cystectomy than men. Similar reports of oncologic differences between men and women following trimodality therapy (TMT) are rare. Our hypothesis was that there would be no difference in overall survival (OS) between sexes receiving TMT. Methods We queried the National Cancer Database (NCDB) for patients diagnosed with clinical stage T2‐T4aN0 M0 MIBC between 2004–2016. We considered patients to have received TMT if they received 55 Gy in 20 fractions or 59.4–70.2 Gy of radiotherapy with concurrent chemotherapy following a transurethral resection of bladder tumor (TURBT). We used multivariable Cox proportional hazard models to determine whether sex was associated with risk of mortality. In addition to OS, we calculated relative survival (RS) to adjust for the fact that females generally survive longer than males. Results Of the patients, 1960 underwent TMT and had survival data. Less than one quarter were female. In the first year following treatment, women had worse OS and RS than men (p = 0.093 and p = 0.030, respectively). However, overall and relative survival differences between sexes were not statistically significantly different in Years 2 and later. Unlike with OS, the RS between sexes remained significant at 9 years; in multivariable analysis based on RS, women were 43% more likely to die than men (p

Abstract Globally consistent measurements of airborne metal concentrations in fine particulate matter (PM2.5) are important for understanding potential health impacts, prioritizing air pollution mitigation strategies, and enabling global chemical transport model development. PM2.5 filter samples (N ~ 800 from 19 locations) collected from a globally distributed surface particulate matter sampling network (SPARTAN) between January 2013 and April 2019 were analyzed for particulate mass and trace metals content. Metal concentrations exhibited pronounced spatial variation, primarily driven by anthropogenic activities. PM2.5 levels of lead, arsenic, chromium, and zinc were significantly enriched at some locations by factors of 100–3000 compared to crustal concentrations. Levels of metals in PM2.5 and PM10 exceeded health guidelines at multiple sites. For example, Dhaka and Kanpur sites exceeded the US National Ambient Air 3-month Quality Standard for lead (150 ng m−3). Kanpur, Hanoi, Beijing and Dhaka sites had annual mean arsenic concentrations that approached or exceeded the World Health Organization’s risk level for arsenic (6.6 ng m−3). The high concentrations of several potentially harmful metals in densely populated cites worldwide motivates expanded measurements and analyses.

Abstract Background The significance of perineural invasion (PNI) in prostate cancer (PC) is unclear. A recent report of patients with pT2N0R0 PC found that PNI at prostatectomy was independently associated with higher Gleason score and more diffuse prostatic disease. We aimed to test our hypothesis that PNI on prostate biopsy in pT2N0R0 patients is associated with increased Gleason score upgrading at prostatectomy. Methods We identified 2892 patients status post prostatectomy with pT2N0R0 PC from three institutions, diagnosed between 1 January 2008 and 31 December 2014. Multivariable logistic regression (MVA) was used to evaluate the association between prostate biopsy PNI status and surgical Gleason upgrading, while controlling for potential confounders. Results Of the 2892 patients identified, 14% had PNI on biopsy, of whom 21% had surgical Gleason upgrading, while 28% without PNI on biopsy had such upgrading (P 4 ng/mL (OR 1.26, P = .02). Conclusions In post‐prostatectomy patients with favorable‐risk PC, PNI on prostate biopsy was not associated with surgical Gleason score upgrading. This may be due to the association of PNI with more diffuse disease, leading to increased biopsy tumor yield and grading accuracy. These findings suggest that in this setting, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision‐making for men debating active surveillance, radiation, and surgery.

Globoid cell leukodystrophy (Krabbe disease) is a fatal neurodegenerative, demyelinating disease caused by dysfunctional activity of galactosylceramidase (GALC), leading to the accumulation of glycosphingolipids including psychosine. While oligodendrocytes have been extensively studied due to their high levels of GALC, the contribution of astrocytes to disease pathogenesis remains to be fully elucidated. In the current study, we generated induced pluripotent stem cells (iPSCs) from two donors with infantile onset Krabbe disease and differentiated them into cultures of astrocytes. Krabbe astrocytes recapitulated many key findings observed in humans and rodent models of the disease, including the accumulation of psychosine and elevated expression of the pro-inflammatory cytokine IL-6. Unexpectedly, Krabbe astrocytes had higher levels of glucosylceramide and ceramide, and displayed compensatory changes in genes encoding glycosphingolipid biosynthetic enzymes, suggesting a shunting away from the galactosylceramide and psychosine pathway. In co-culture, Krabbe astrocytes negatively impacted the survival of iPSC-derived human neurons while enhancing survival of iPSC-derived human microglia. Substrate reduction approaches targeting either glucosylceramide synthase or serine palmitoyltransferase to reduce the sphingolipids elevated in Krabbe astrocytes failed to rescue their detrimental impact on neuron survival. Our results suggest that astrocytes may contribute to the progression of Krabbe disease and warrant further exploration into their role as therapeutic targets.

We present a first look at the MRS observations of the nucleus of the nearby galaxy M83, taken with MIRI on board JWST. The observations show a rich set of emission features from the ionized gas, warm molecular gas, and dust. To begin dissecting the complex processes in this part of the galaxy, we divide the observations into four different regions. We find that the strength of the emission features varies strongly from region to region, with the southeast region displaying the weakest features tracing the dust continuum and interstellar medium (ISM) properties. Comparison between the cold molecular gas traced by the ^12 CO (1–0) transition with the Atacama Large Millimeter/submillimeter Array and the H _2 S(1) transition shows a similar spatial distribution. This is in contrast to the distribution of the much warmer H _2 emission from the S(7) transition found to be concentrated around the optical nucleus. We use the rotational emission lines and model the H _2 excitation to estimate a total molecular gas mass accounting for the warm H _2 component of M (>50 K) ${}_{{{\rm{H}}}_{2}}$ = 67.90 (±5.43) × 10 ^6 M _⊙ . We compare this value to the total gas mass inferred by probing the cold H _2 gas through the ^12 CO (1–0) emission, M (CO) ${}_{{{\rm{H}}}_{2}}$ = 17.15 × 10 ^6 M _⊙ . We estimate that ∼75% of the total molecular gas mass is contained in the warm H _2 component. We also identify [O iv ] 25.89 μ m and [Fe ii ] 25.99 μ m emission. We propose that the diffuse [Fe ii ] 25.99 μ m emission might be tracing shocks created during the interactions between the hot wind produced by the starburst and the much cooler ISM above the galactic plane. More detailed studies are needed to confirm such a scenario.

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

Water is an increasingly precious resource in California as years of drought, climate change, pollution, as well as an expanding population have all stressed the state's drinking water supplies. Currently, there are increasing concerns about whether regulated and unregulated contaminants in drinking water are linked to a variety of human-health outcomes particularly in socially disadvantaged communities with a history of health risks. To begin to address this data gap by broadly assessing contaminant mixture exposures, the current study was designed to collect tapwater samples from communities in Gold Country, the San Francisco Bay Area, two regions of the Central Valley (Merced/Fresno and Kern counties), and southeast Los Angeles for 251 organic chemicals and 32 inorganic constituents. Sampling prioritized low-income areas with suspected water quality challenges and elevated breast cancer rates. Results indicated that mixtures of regulated and unregulated contaminants were observed frequently in tapwater throughout the areas studied and the types and concentrations of detected contaminants varied by region, drinking-water source, and size of the public water system. Multiple exceedances of enforceable maximum contaminant level(s) (MCL), non-enforceable MCL goal(s) (MCLG), and other health advisories combined with frequent exceedances of benchmark-based hazard indices were also observed in samples collected in all five of the study regions. Given the current focus on improving water quality in socially disadvantaged communities, our study highlights the importance of assessing mixed-contaminant exposures in drinking water at the point of consumption to adequately address human-health concerns (e.g., breast cancer risk). Data from this pilot study provide a foundation for future studies across a greater number of communities in California to assess potential linkages between breast cancer rates and tapwater contaminants.

Background: Patients with immune thrombocytopenia (ITP) are at risk of bleeding and, paradoxically, thromboembolic events (TEEs), irrespective of thrombocytopenia. The risk of thrombosis is increased by advanced age, obesity, and prothrombotic comorbidities: cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease, among others. Certain ITP treatments further increase the risk of TEE, especially splenectomy and thrombopoietin receptor agonists. Spleen tyrosine kinase (SYK) is a key signaling molecule common to thromboembolic and hemostatic (in addition to inflammatory) pathways. Fostamatinib is an orally administered SYK inhibitor approved in the USA and Europe for treatment of chronic ITP in adults. Methods: The phase III and extension studies included heavily pretreated patients with long-standing ITP, many of whom had risk factors for thrombosis prior to initiating fostamatinib. This report describes long-term safety and efficacy of fostamatinib in 146 patients with up to 5 years of treatment, a total of 229 patient-years, and assesses the incidence of thromboembolic events (by standardized MedDRA query). Results: Platelet counts ⩾50,000/µL were achieved in 54% of patients and the safety profile was as described in the phase III clinical studies with no new toxicities observed over the 5 years of follow-up. The only TEE occurred in one patient (0.7%, or 0.44/100 patient-years), who experienced a mild transient ischemic attack. This is a much lower rate than might be expected in ITP patients. Conclusion: This report demonstrates durable efficacy and a very low incidence of TEE in patients receiving long-term treatment of ITP with the SYK inhibitor fostamatinib. ClinicalTrials.gov identifiers: NCT02076399, NCT02076412, and NCT02077192.

The objective of this study was to evaluate 4 pre-exercise hydration strategies (oral water, chicken-flavored water, chicken-flavored oral electrolyte solution, and subcutaneous electrolyte solution) in working dogs conducting rigorous tracking operations in hot and arid conditions. In a randomized cross-over field study, 7 Border Patrol Search, Trauma, and Rescue (BORSTAR) Unit dogs working/training out of Fort Bliss in El Paso, Texas were randomly assigned to one of 4 different hydration strategy treatments each day for 4 days of study participation. Dogs were provided hydration treatment prior to running 2 separate one-mile tracks and were offered water while tracking. Body weight, blood, and urine were collected at the beginning of the study day and at the completion of each track. Core body temperatures were recorded using internal temperature sensing capsules. The impact of hydration strategy on change in weight, peak temperature, and serum chemical, hematological, and urinary parameters were analyzed using the COIN procedure in Ra. Compared to the other 3 hydration strategies, dogs receiving chicken-flavored water had higher blood creatine kinase values at the end of the second track (p = 0.0361). Otherwise, hydration strategy had minimal effects on blood or urine parameters. Total fluid intake was lower with water only compared to the other three hydration strategies. Dogs developed elevated core body temperatures (median 41°C; 106°F) without signs of heat exhaustion or heat stroke. Alternate hydration strategies increased total fluid intake compared to water alone; however, chicken-flavored water resulted in increased markers of muscle injury suggesting electrolyte-enriched strategies may have an advantage as a hydration strategy. Additionally, electrolyte-enriched fluids before exercise may help these dogs maintain lower peak temperatures.

Background. Though there is an effective intervention, pain after surgical intervention is undermanaged worldwide. A systematic implementation is required to increase the utilization of available evidence-based intervention to manage the inevitable pain after surgery. The aim of this research project is to develop a scalable model for managing pain after cesarean section by implementing the World Health Organization’s (WHO) pain management guidelines through a combination of implementation research and quality improvement methods. Methods. We implemented the World Health Organization (WHO) pain management guidelines using effective implementation strategies. First, we conducted a formative qualitative exploration to identify enablers and obstacles. In addition, we took base-line assessment on pain management implementation process and outcome using a checklist prepared from the guideline and an adapted American Pain Outcome assessment tool version 2010, respectively. Then, we integrated the guidelines into the existing practice by using collaborative iterative learning strategy. We analyzed the data by Statistical Packages for Social Sciences (SPSS) version 21. We compared the before and after data using chi-squared and Fischer’s exact test. A change in any measurement was considered as significant at p value 0.05. Result. We collected data from 106 mothers before and 110 mothers after intervention implementation. We successfully integrated pain as a fifth vital sign in more than 87% (p value

Introduction: Mild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS). Materials and methods: Children aged 8–16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (

Dwarf galaxies are by far the most numerous galaxies in the Universe, showing properties that are quite different from those of their larger and more luminous cousins. This review focuses on the physical and chemical properties of the interstellar medium of those dwarfs that are known to host significant amounts of gas and dust. The neutral and ionized gas components and the impact of the dust will be discussed, as well as first indications for the existence of active nuclei in these sources. Cosmological implications are also addressed, considering the primordial helium abundance and the similarity of local Green Pea galaxies with young, sometimes protogalactic sources in the early Universe.

Abstract Background Reducing caloric intake is a proven intervention for mitigating and modulating morbidities associated with overnutrition. Caloric restriction is difficult to affect clinically, therefore, dietary interventions that ameliorate the adverse consequences of overnutrition in the presence of a high-calorie diet would be of value. Methods Mice were fed an obesogenic diet containing 60% fat + 10% cellulose (HFC), or a control diet containing 10% fat + 10% cellulose (LFC) for 12 wks. Subgroups of mice were then switched from HFC to each of the following diets for an additional 5 wks: 1) 60% fat + 10% pectin (HFP), 2) LFC or 3) 10% fat + 10% pectin (LFP). To test for statistical differences, one-way or two-way ANOVAs were used with or without repeated measurements as needed. Results In comparison to HFC, HFP prevented additional weight gain while LFC and LFP triggered weight loss of 22.2 and 25.4%, respectively. Mice continued on HFC experienced a weight increase of 26% during the same 5 wk. interval. After 12 wks, HFC decreased mouse locomotion by 18% when compared to control diet, but a diet switch to LFC or LFP restored mouse movement. Importantly, HFP, LFC, and LFP reduced fasting blood glucose when compared to HFC. Likewise, HFP, LFC and LFP improved glucose tolerance and decreased fatty liver by 37.9, 49.8, 53.6 and 20.2%, 37.2, 43.7%, respectively. Conclusions Taken together, the results indicate that the dietary fiber pectin can mitigate some adverse consequences of overnutrition even in the presence of high-fat.

Objective: Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease, including obesity, hypertension, dyslipidemia, and hyperglycemia. While sizable prior literature has examined associations between individual risk factors and quantitative measures of cortical thickness (CT), only very limited research has investigated such measures in MetS. Furthermore, the relative contributions of these risk factors to MetS-related effects on brain morphology have not yet been studied. The primary goal of this investigation was to examine how MetS may affect CT. A secondary goal was to explore the relative contributions of individual risk factors to regional alterations in CT, with the potential to identify risk factor combinations that may underlie structural changes. Methods: Eighteen participants with MetS (mean age=59.78years) were age-matched with 18 healthy control participants (mean age=60.50years). CT measures were generated from T1-weighted images and groups were contrasted using whole-brain general linear modeling. A follow-up multivariate partial least squares correlation (PLS) analysis, including the full study sample with complete risk factor measurements (N=53), was employed to examine which risk factors account for variance in group structural differences. Results: Participants with MetS demonstrated significantly reduced CT in left hemisphere inferior parietal, rostral middle frontal, and lateral occipital clusters and in a right hemisphere precentral cluster. The PLS analysis revealed that waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose were significant contributors to reduced CT in these clusters. In contrast, diastolic blood pressure showed a significantly positive association with CT while systolic blood pressure did not emerge as a significant contributor. Age was not associated with CT. Conclusion: These results indicate that MetS can be associated with regionally specific reductions in CT. Importantly, a novel link between a risk factor profile comprising indices of obesity, hyperglycemia, dyslipidemia and diastolic BP and localized alterations in CT emerged. While the pathophysiological mechanisms underlying these associations remain incompletely understood, these findings may be relevant for future investigations of MetS and might have implications for treatment approaches that focus on specific risk factor profiles with the aim to reduce negative consequences on the structural integrity of the brain. Keywords: Obesity, Dyslipidemia, Hyperglycemia, Diastolic blood pressure, Gray matter, Magnetic resonance imaging

Improving the quality of life in urban areas has become a major concern in the last few decades. With a constantly increasing urban population and in a climate change context, detailed knowledge of the impact of urban elements on the outdoor thermal environment is relevant. In this work, we present the results of several climatic campaigns carried out in Singapore aiming to evaluate local urban climate variables. Sensors were deployed simultaneously in different sites. The effect of building shadowing in the diurnal cycle of mean radiant temperature (Tmrt) is evaluated in different seasons. Although during the Inter-Monsoon season, mean Tmrt reduction due to building shadow is ≈19 °C, during clear skies days, it can be reduced by ≈30 °C. The Tmrt difference between sites is analyzed based on the weather conditions, the sky view factor (SVF), and the type of surrounding urban elements. Under building shadow conditions, higher SVF showed higher Tmrt values, although no correlation was found between Tmrt and diffuse solar radiation (measured above the urban canopy). The results suggest a relevant contribution of other radiation components (e.g., longwave radiation). The quantitative analysis of the Tmrt provided in this work is relevant for outdoor thermal comfort strategies in tropical areas such as Singapore.

OmpR is a transcription factor activated in acid and osmotic responses of Gram-negative bacteria, leading to acidification of the bacterial cytoplasm. Here the authors use single cell pH imaging to define the role of OmpR-regulated genes in the acidification response to osmotic and acid stress of Salmonella and E. coli.

Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA) into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH), organic cation transporter (OCTN2), and peroxisome proliferator-activated receptor (PPARα), a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

EF-hand Ca2+-binding protein family members, α- and β-parvalbumins have been studied for decades. Yet, considerable information is lacking distinguishing functional differences between mammalian α-parvalbumin (PVALB) and oncomodulin (OCM), a branded β-parvalbumin. Herein, we provide an overview detailing the current body of work centered around OCM as an EF-Hand Ca2+-binding protein and describe potential mechanisms of OCM function within the inner ear and immune cells. Additionally, we posit that OCM is evolutionarily distinct from PVALB and most other β-parvalbumins. This review summarizes recent studies pertaining to the function of OCM and emphasizes OCM as a parvalbumin possessing a unique cell and tissue distribution, Ca2+ buffering capacity and phylogenetic origin.

Multisubunit members of the CATCHR family: COG and NRZ complexes, mediate intra-Golgi and Golgi to ER vesicle tethering, respectively. We systematically addressed the genetic and functional interrelationships between Rabs, Kifs, and the retrograde CATCHR family proteins: COG3 and ZW10, which are necessary to maintain the organization of the Golgi complex. We scored the ability of siRNAs targeting 19 Golgi-associated Rab proteins and all 44 human Kifs, microtubule-dependent motor proteins, to suppress CATCHR-dependent Golgi fragmentation in an epistatic fluorescent microscopy-based assay. We found that co-depletion of Rab6A, Rab6A’, Rab27A, Rab39A and two minus-end Kifs, namely KIFC3 and KIF25, suppressed both COG3- and ZW10-depletion-induced Golgi fragmentation. ZW10-dependent Golgi fragmentation was suppressed selectively by a separate set of Rabs: Rab11A, Rab33B and the little characterized Rab29. 10 Kifs were identified as hits in ZW10-depletion-induced Golgi fragmentation, and, in contrast to the double suppressive Kifs, these were predominantly plus-end motors. No Rabs or Kifs selectively suppressed COG3-depletion-induced Golgi fragmentation. Protein-protein interaction network analysis indicated putative direct and indirect links between suppressive Rabs and tether function. Validation of the suppressive hits by EM confirmed a restored organization of the Golgi cisternal stack. Based on these outcomes, we propose a three-way competitive model of Golgi organization in which Rabs, Kifs and tethers modulate sequentially the balance between Golgi-derived vesicle formation, consumption, and off-Golgi transport.

Further characterization of essential systems in the parasitic filarial nematode Brugia malayi is needed to better understand its biology, its interaction with its hosts, and to identify critical components that can be exploited to develop novel treatments. The production of glycophosphatidylinositol-anchored proteins (GPI-APs) is essential for eukaryotic cellular and physiological function. In addition, GPI-APs perform many important roles for cells. In this study, we characterized the B. malayi GPI-anchored proteome using both computational and experimental approaches. We used bioinformatic strategies to show the presence or absence of B. malayi GPI-AP biosynthetic pathway genes and to compile a putative B. malayi GPI-AP proteome using available prediction programs. We verified these in silico analyses using proteomics to identify GPI-AP candidates prepared from the surface of intact worms and from membrane enriched extracts. Our study represents the first description of the GPI-anchored proteome in B. malayi and lays the groundwork for further exploration of this essential protein modification as a target for novel anthelmintic therapeutic strategies.

Global climate is changing as a result of anthropogenic warming, leading to higher daily excursions of temperature in cities. Such elevated temperatures have great implications on human thermal comfort and heat stress, which should be closely monitored. Current methods for heat exposure assessments (surveys, microclimate measurements, and laboratory experiments), however, present several limitations: measurements are scattered in time and space and data gathered on outdoor thermal stress and comfort often does not include physiological and behavioral parameters. To address these shortcomings, Project Coolbit aims to introduce a human-centric approach to thermal comfort assessments. In this study, we propose and evaluate the use of wrist-mounted wearable devices to monitor environmental and physiological responses that span a wide range of spatial and temporal distributions. We introduce an integrated wearable weather station that records (a) microclimate parameters (such as air temperature and humidity), (b) physiological parameters (heart rate, skin temperature and humidity), and (c) subjective feedback. The feasibility of this methodology to assess thermal comfort and heat stress is then evaluated using two sets of experiments: controlled-environment physiological data collection, and outdoor environmental data collection. We find that using the data obtained through the wrist-mounted wearables, core temperature can be predicted non-invasively with 95 percent of target attainment within ±0.27 °C. Additionally, a direct connection between the air temperature at the wrist ( T _a _, _w ) and the perceived activity level (PAV) of individuals was drawn. We observe that with increased T _a _, _w , the desire for physical activity is significantly reduced, reaching ‘Transition only’ PAV level at 36 °C. These assessments reveal that the wearable methodology provides a comprehensive and accurate representation of human heat exposure, which can be extended in real-time to cover a large spatial distribution in a given city and quantify the impact of heat exposure on human life.

Microbial electrochemical technologies have revealed the opportunity of electrochemical enrichment for specific bacterial groups that are able to catalyze reactions of interest. However, there are unsolved challenges towards their application under aggressive environmental conditions, such as in the sea. This study demonstrates the impact of surface electrochemical potential on community composition and its corrosivity. Electrochemical bacterial enrichment was successfully carried out in natural seawater without nutrient amendments. Experiments were carried out for ten days of exposure in a closed-flow system over 316L stainless steel electrodes under three different poised potentials (−150 mV, +100 mV, and +310 mV vs. Ag/AgCl). Weight loss and atomic force microscopy showed a significant difference in corrosion when +310 mV (vs. Ag/AgCl) was applied in comparison to that produced under the other tested potentials (and an unpoised control). Bacterial community analysis conducted using 16S rRNA gene profiles showed that poised potentials are more positive as +310 mV (vs. Ag/AgCl) resulted in strong enrichment for Rhodobacteraceae and Sulfitobacter. Hence, even though significant enrichment of the known electrochemically active bacteria from the Rhodobacteraceae family was accomplished, the resultant bacterial community could accelerate pitting corrosion in 316 L stainless steel, thereby compromising the durability of the electrodes and the microbial electrochemical technologies.

The effects of tidal cycles associated with the water level on the biocorrosion of stainless steel AISI 316L were studied. Steel coupons were exposed to different conditions of immersion in mesocosms fed by fresh seawater either continuously or in accordance with the periodicity of natural tides. After 5 and 15 weeks, all coupons were found to have undergone ennoblement associated with the formation of a biofilm. Analysis of the composition of the bacterial community using denaturing gradient gel electrophoresis (DGGE) revealed differences in the biological succession. After 15 weeks, exposure to the simulated tidal conditions resulted in biofilms with lesser bacterial richness; the corresponding rate of corrosion, as determined by weight loss, was about 40 times lower compared to the case for the continuous exposure to seawater. Phylogenetic analysis of selected DGGE bands and the inspection of biofilm morphologies revealed that the faster rate of corrosion was associated with the presence of iron-oxidizing Zetaproteobacteria and eukaryotic photosynthetic microorganisms. On the other hand, intermittent exposure to seawater resulted in the succession of microorganisms resistant to the stress associated with sudden environmental changes, which was associated with a low rate of corrosion.