The All of Us Research Program (All of Us) is a national effort to accelerate health research by exploring the relationship between lifestyle, environment, and genetics. It is set to become one of ...the largest research efforts in U.S. history, aiming to build a national resource of data from at least one million participants. All of Us aims to address the need for more diversity in research and set the stage for that diversity to be leveraged in precision medicine research to come. This paper describes how the program assessed demographic characteristics of participants who have enrolled in other U.S. biomedical research cohorts to better understand which groups are traditionally represented or underrepresented in biomedical research. We 1) reviewed the enrollment characteristics of national cohort studies like All of Us, and 2) surveyed the literature, focusing on key diversity categories essential to the program's enrollment aims. Based on these efforts, All of Us emphasizes enrollment of racial and ethnic minorities, and has formally designated the following additional groups as historically underrepresented: individuals-with inadequate access to medical care; under the age of 18 or over 65; with an annual household income at or below 200% of the federal poverty level; who have a cognitive or physical disability; have less than a high school education or equivalent; are intersex; identify as a sexual or gender minority; or live in rural or non-metropolitan areas. Research accounting for wider demographic variability is critical. Only by ensuring diversity and by addressing the very barriers that limit it, can we position All of Us to better understand and tackle health disparities.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of ...monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK2 Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC / bunch ) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.
Lawsonia intracellularis is the causative agent of proliferative enteropathy, an endemic disease in pigs and an emerging concern in horses. Enterocyte hyperplasia is a common lesion in every case but ...there are differences regarding clinical and pathological presentations among affected species. We hypothesize that host susceptibility to L. intracellularis infection depends on the species of origin of the bacterial isolate. The objective of this study was to evaluate the susceptibilities of pigs and horses to L. intracellularis infection using either a porcine or an equine isolate.
Twelve foals and eighteen pigs were equally divided into three groups and infected with either a porcine or an equine isolate (109L. Intracellularis/challenged animal), and a saline solution (negative control group). The animals were monitored regarding clinical signs, average of daily weight gain, fecal shedding of the bacteria by PCR and humoral serological response.
Foals infected with the equine isolate developed moderate to severe clinical signs and maintained a lower average of weight gain compared to control foals. Fecal quantitative PCR in equine isolate-infected foals revealed higher amounts of bacterial DNA associated with longer duration of shedding compared with porcine isolate-infected foals. All four foals infected with the equine isolate demonstrated higher IgG titers in the serum compared with porcine isolate-infected foals. In the pig trial, diarrhea and seroconversion were only observed in animals infected with the porcine isolate. Pathological changes typical of proliferative enteropathy were observed in the necropsied foal infected with equine isolate and in the two necropsied pigs infected with the porcine isolate.
Evident clinical signs, longer periods of bacterial shedding and stronger serologic immune responses were observed in animals infected with species-specific isolates. These results show that host susceptibility is driven by the origin of the isolated L. intracellularis strain.
There is growing public demand that research participants receive all of their results, regardless of whether clinical action is indicated. Instead of the standard practice of returning only ...actionable results, we propose a reconceptualization called "return of value" to encompass the varied ways in which research participants value specific results and more general information they receive beyond actionable results. Our proposal is supported by a national survey of a diverse sample, which found that receiving research results would be valuable to most (78.5 percent) and would make them more likely to trust researchers (70.3 percent). Respondents highly valued results revealing genetic effects on medication response and predicting disease risk, as well as information about nearby clinical trials and updates on how their data were used. The information most valued varied by education, race/ ethnicity, and age. Policies are needed to enable return of information in ways that recognize participants' differing informational needs and values.
In 2013, the U.S. Environmental Protection Agency (USEPA) updated its national recommended water quality criteria for the protection of aquatic life from the toxic effects of ammonia in freshwaters. ...From its updated national dataset, USEPA determined freshwater mussels in the family Unionidae were the most sensitive taxa to ammonia. Thus, it has become necessary to determine whether freshwater mussels exist in waterbodies near discharge locations from Publically Owned Treatment Works (POTWs), to ensure that POTWs are regulated appropriately with regard to ammonia levels in their treated effluent. However, because mussels are notoriously difficult to detect using traditional survey methodologies, most POTWs have not determined whether freshwater mussels exist in their receiving waters. Environmental DNA (eDNA) presents a promising methodology to survey for freshwater mussels in POTW receiving waters. We developed and validated a quantitative polymerase chain reaction (qPCR) assay for the three freshwater mussel taxa that are currently known to exist in California's Central Valley. We then placed a cage with 20 Gonidea angulata into a riverine environment and collected water samples at evenly spaced downstream intervals to determine how habitat type and distance from the caged mussels affected eDNA detection. Using two‐stage occupancy modeling, we determined higher detection probabilities occur in riffle habitats compared to pool or run habitats. We also found surface samples work well for collecting freshwater mussel eDNA in riffle habitats, but are less likely to capture mussel eDNA in pools or runs. The maximum downstream distance at which the eDNA from the 20 placed G. angulata mussels was detected was 8 km. Our study demonstrates that eDNA is a reliable tool for determining freshwater mussel presence in riverine systems, but that sampling should consider habitat type, distance between sampling locations, and time of year for the most effective results.
We developed and validated a quantitative polymerase chain reaction (qPCR) assay for the three freshwater mussel taxa that are currently known to exist in California's Central Valley. We then placed a cage with 20 Gonidea angulata into a riverine environment and collected water samples at evenly spaced downstream intervals to determine how habitat type and distance from the caged mussels affected eDNA detection. Using occupancy modeling, we determined higher detection probabilities occur in riffle habitats compared to pool or run habitats.
Treatment of oxazole or 5-aryl oxazoles with i-PrMgCl smoothly generates the corresponding 2-Grignard reagents, which react with Weinreb amides to provide exclusively 2-acyl oxazole products.
This study was designed to clarify whether speech understanding in a fluctuating background is related to temporal processing as measured by the detection of gaps in noise bursts. Fifty adults with ...normal hearing or mild high-frequency hearing loss served as subjects. Gap detection thresholds were obtained using a three-interval, forced-choice paradigm. A 150-ms noise burst was used as the gap carrier with the gap placed close to carrier onset. A high-frequency masker without a temporal gap was gated on and off with the noise bursts. A continuous white-noise floor was present in the background. Word scores for the subjects were obtained at a presentation level of 55 dB HL in competing babble levels of 50, 55, and 60 dB HL. A repeated measures analysis of covariance of the word scores examined the effects of age, absolute sensitivity, and temporal sensitivity. The results of the analysis indicated that word scores in competing babble decreased significantly with increases in babble level, age, and gap detection thresholds. The effects of absolute sensitivity on word scores in competing babble were not significant. These results suggest that age and temporal processing influence speech understanding in fluctuating backgrounds in adults with normal hearing or mild high-frequency hearing loss.
Fish adjust rates of somatic growth in the face of changing food consumption. As in other vertebrates, growth in fish is regulated by the growth hormone (Gh)/insulin-like growth factor-1 (Igf1) ...endocrine axis, and changes in food intake impact growth via alterations to Gh/Igf1 signaling. Understanding the time course by which the Gh/Igf1 axis responds to food consumption is crucial to predict how rapidly changes in food abundance might lead to altered growth dynamics. Here, we looked at the response times of plasma Igf1 and liver Igf1 signaling-associated gene expression to refeeding after food deprivation in juvenile gopher rockfish (Sebastes carnatus), one of several species of northern Pacific Ocean Sebastes rockfishes targeted by fisheries or utilized for aquaculture. Gopher rockfish were fasted for 30 d, after which a subset was fed to satiation for 2 h, while other rockfish continued to be fasted. Refed fish exhibited higher hepatosomatic index (HSI) values and increased Igf1 after food consumption. Gene transcripts for Gh receptor 1 (ghr1), but not ghr2, increased in the liver 2-4 d after eating. Transcripts encoding igf1also increased in the liver of refed fish by 4 d after feeding, only to return to levels similar as continually fasted rockfish by 9 d after feeding. Liver mRNA abundances for Igf binding protein (Igfbp) genes igfbp1a, igfbp1b, and igfbp3a declined within 2 d of feeding. These findings provide evidence that circulating Igf1 in rockfish reflects a fish's feeding experience within the previous few days, and suggest that feeding-induced increases in Igf1 are being mediated in part by altered liver sensitivity to Gh due to upregulated Gh receptor 1 expression.
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•Food deprived gopher rockfish increased plasma Igf1 upon refeeding.•Liver gene transcripts encoding igf1 increased within 2 d after eating.•Refeeding upregulated hepatic mRNAs for Gh receptor 1 (ghr1) – but not ghr2.•Igf binding protein igfbp1a, −1b, and -3a mRNAs in liver were downregulated by refeeding.•Upregulation of Gh receptor 1 may temporarily enhance liver Igf1 release after fasting.
Human adrenarche is associated with the establishment of a functional zona reticularis (ZR) and increasing secretion of dehydroepiandrosterone (DHEA) in sulfated form (DS). Like most non-human ...primates, rhesus macaques are not believed to undergo adrenarche, though they clearly establish a functional ZR after birth. However, the origins of the rhesus ZR are not well defined. Therefore, we investigated the zonal development, steroidogenic enzyme expression and morphology of rhesus adrenals from 1 day to 14 months of age. Immunohistochemistry was conducted to determine expression profiles of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), cytochrome P450, family 21, subfamily A, polypeptide 2 (CYP21A2), hydroxy-Δ-5-steroid dehydrogenase, 3β- and steroid Δ-isomerase 2 (HSD3B2), the redox partner NADPH-cytochrome P450 oxidoreductase (CPR), as well as the accessory protein cytochrome b5 (b5), a marker of the primate ZR. The rhesus ZR is mature by 3 months of age based on differentiation of the innermost zone that lacks HSD3B2, but exhibits increased b5 expression during this period. Further, the ZR develops in neonates from a previously described dense band of cells which we show expresses b5, CYP17A1, CPR, and CYP21A2 throughout maturation. The fetal zone (FZ) is distinguished from the ZR by its lack of CYP21A2, and ZR development proceeded as the FZ regressed with two important implications: neither FZ regression nor ZR maturation can be monitored independently by circulating adrenal androgens, and these events must be induced by different factors in rhesus, and likely humans. Collectively these data demonstrate that ZR development begins before birth in the rhesus, proceeding concomitantly with FZ regression post-natally, suggesting that rhesus experiences morphological adrenarche during the first three months of life.
Equine coronavirus (ECoV) is considered an enteric pathogen of foals and has only recently been associated with infections in adult horses. Seroprevalence data is needed to better understand the ...epidemiology of ECoV in adult horses, evaluate diagnostic modalities and develop preventive measures. The objective of this study was to investigate the seroprevalence and selective risk factors for ECoV in 5247 healthy adult horses in the USA, using a recently established and validated IgG enzyme-linked immunosorbent assay. Prevalence factors analysed in this study included geographic region, age, breed, sex and use. A total of 504/5247 horses (9.6%) horses tested seropositive. Geographic region (Mid-West; P = 0.008), breed (Draft horses; P = 0.003) and specific uses of horses (ranch/farm, P = 0.034; breeding use, P = 0.016) were all statistically significant risk factors for seropositivity.
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