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For a finite group $G$, let $\sigma(G)$ be the number of subgroups of $G$ and $\sigma_\iota(G)$ the number of isomorphism types of subgroups of $G$. Let $L=L_r(p^e)$ denote a simple group of Lie type, rank $r$, over a field of order $p^e$ and characteristic $p$. If $r\neq 1$, $L\not\cong {^2 B_2}(2^{1+2m})$, then there are constants $c,d$, dependent on the Lie type, such that as $re$ grows $$p^{(c-o(1))r^4e^2}\leq\sigma_{\iota}(L_r(p^e))\leq\sigma(L_r(p^e)) \leq p^{(d+o(1))r^4e^2}.$$ For type $A$, $c=d=1/64$. For other classical groups $1/64\leq c\leq d\leq 1/4$. For exceptional and twisted groups $1/2^{100}\leq c\leq d\leq 1/4$. Furthermore, $$2^{(1/36-o(1))k^2)}\leq\sigma_{\iota}(\mathrm{Alt}_k)\leq \sigma(\mathrm{Alt}_k)\leq 24^{(1/6+o(1))k^2}.$$ For abelian and sporadic simple groups $G$, $\sigma_{\iota}(G),\sigma(G)\in O(1)$. In general these bounds are best possible amongst groups of the same orders. Thus with the exception of finite simple groups with bounded ranks and field degrees, the subgroups of finite simple groups are as diverse as possible.

Introduction: Women living with human immunodeficiency virus (WLHIV) may face additional challenges and differential birth outcomes when compared with women without human immunodeficiency virus (HIV). There is limited research to date studying birth outcomes among a nationally representative sample of WLHIV. This study compares stillbirth and prematurity rates between HIV-positive (HIV+) and HIV-negative (HIV−) mothers in the Medicaid program. Methods: We used 12 years (2001–2012) of Medicaid Analytic eXtract data. We included Medicaid claims from the 14 states with the highest prevalence of HIV: California, Florida, Georgia, Illinois, Louisiana, Massachusetts, Maryland, North Carolina, New Jersey, New York, Ohio, Pennsylvania, Texas, and Virginia. Primary outcomes were stillbirth and preterm birth. We used logistic regression models adjusting for age, race, Medicaid coverage, eligibility, substance use, rurality, comorbidities, and state fixed effects to compare differences in rates for women with and without HIV. Results: Our study included a total of 33,078 HIV+ and 7,663,758 HIV− pregnancies from Medicaid enrollees between 2001 and 2012. The proportions of stillbirths and preterm births were higher for HIV+ when compared with HIV− mothers (0.9% vs. 0.7% and 8.0% vs. 6.6%, p

Consumer demand for novel, visually attractive ornamentals has often overshadowed the functional value plants may provide for flower-visiting insects. As native and nonnative species are hybridized for form, color, flowering, and disease resistance, it is important to assess whether some of these alterations influence plant nutrient quality for foraging insect pollinators. A study was conducted to ascertain the resource value of ornamental cultivars compared with their native congeners. The nectar volume and pollen quantity, viability, and protein content of 10 species of popular herbaceous flowering plants, commonly advertised as pollinator-friendly, were evaluated in northcentral Florida. Each genus encompassed a native and nonnative species, apart from pentas. Native species included blanket flower (Gaillardia pulchella), lanceleaf coreopsis (Coreopsis lanceolata), pineland lantana (Lantana depressa), and scarlet sage (Salvia coccinea). Nonnative species included Barbican™ yellow-red ring blanket flower (Gaillardia aristata ‘Gaiz005’), Bloomify™ rose lantana (Lantana camara ‘UF-1011-2’), mysty salvia (Salvia longispicata × farinacea ‘Balsalmysty’), Lucky Star® dark red pentas (Pentas lanceolata ‘PAS1231189’), ruby glow pentas (Pentas lanceolata ‘Ruby glow’) and UpTick™ Gold & Bronze coreopsis (Coreopsis × ‘Baluptgonz’). Floral rewards differed significantly across species. The native scarlet sage exhibited the largest nectar volume per flower in the summer (2.13 ± 0.17 µL), followed by the nonnative mysty salvia (1.26 ± 0.17 µL). In the fall, ruby glow pentas exhibited the largest nectar volume per flower (1.09 ± 0.17 µL) compared with all other ornamentals. The composite flowers of the native and nonnative blanket flower and coreopsis species had the lowest nectar volume per flower regardless of sampling date. Likewise, ruby glow pentas displayed the highest quantity of pollen grains (96.29 ± 0.12) per sample, followed by Lucky star pentas (52.33 ± 0.12), and Barbican blanket flower (50.98 ± 0.12). Pollen viability was similarly high (92% to 98%) among all species, apart from Bloomify rose lantana (20%) and pineland lantana (48%). Pollen protein content was highest in Uptick coreopsis (11.378 ± 1.860 μg/mg dry weight) and Lucky star pentas (10.656 ± 3.726 μg/mg dry weight), followed by lanceleaf coreopsis (7.918 ± 1.793 μg/mg dry weight). These results largely showed that the nonnative ornamentals selected provided resource-rich floral rewards, comparable to native congeners. Still, care should be taken in making similar assessments of other modern floral types.

Diverse floral resources impart immense value for pollinating insects of all types. With increasing popularity and demand for modern ornamental hybrids, cultivation by breeders has led to selection for a suite of traits such as extended bloom periods and novel colors and forms deemed attractive to the human eye. Largely understudied is pollinator preference for these new cultivars, as compared with their native congeners. To address this gap in understanding, 10 species of popular herbaceous flowering plants, commonly labeled as pollinator-friendly, were evaluated at two sites in Florida [U.S. Department of Agriculture (USDA) cold hardiness zones 8b and 9a] and across three seasons for their floral abundance and overall attractiveness to different groups of pollinating insects. Each genus, apart from pentas, encompassed a native and nonnative species. Native species included blanket flower (Gaillardia pulchella), lanceleaf coreopsis (Coreopsis lanceolata), pineland lantana (Lantana depressa), and scarlet sage (Salvia coccinea). Nonnative species included Barbican™ yellow-red ring blanket flower (G. aristata ‘Gaiz005’), Bloomify™ rose lantana (L. camara ‘UF-1011-2’), mysty salvia (S. longispicata ×farinacea ‘Balsalmysty’), Lucky Star® dark red pentas (Pentas lanceolata ‘PAS1231189’), ruby glow pentas (P. lanceolata ‘Ruby glow’) and Uptick™ Gold & Bronze coreopsis (Coreopsis × ‘Baluptgonz’). Flower-visiting insects were recorded during five-minute intervals in the morning and categorized into the following morpho-groups: honey bees, large-bodied bees (bumble and carpenter bees), other bees (small to medium-bodied native bees), butterflies/moths, and wasps. Floral abundance and pollinator visitation varied widely by season, location, and species. Of the plant species evaluated, nonnative plants produced nearly twice as many flowers as native plants. About 22,000 floral visitations were observed. The majority of visits were by native, small to medium-bodied bees (55.28%), followed by butterflies and moths (15.4%), large-bodied native bees (11.8%), wasps (10.0%), and honey bees (7.6%). Among plant genera, both native and nonnative coreopsis and blanket flower were most attractive to native, small to medium-bodied bees (e.g., sweat bees, leafcutter bees) with the greatest number of visitations occurring during the early and midmonths of the study (May–August). Across the study, butterflies and moths visited lantana more frequently than all other ornamentals evaluated, whereas pentas were most attractive to wasps. Large-bodied bees visited plants most frequently in May and June, primarily foraging from both native and nonnative salvia. While results from this study showed nominal differences between native and nonnative species in their ability to attract the studied pollinator groups, care should be taken to making similar assessments of other modern plant types.

PDF file - 37K, CAR spleen infiltrating lymphocytes have lower levels of inhibitory receptors than CAR tumor infiltrating lymphocytes.

PDF file - 38K, CAR TILs upregulate inhibitory receptors.

Purpose: Immunotherapy using vaccines or adoptively transferred tumor-infiltrating lymphocytes (TIL) is limited by T-cell functional inactivation within the solid tumor microenvironment. The purpose of this study was to determine whether a similar tumor-induced inhibition occurred with genetically modified cytotoxic T cells expressing chimeric antigen receptors (CAR) targeting tumor-associated antigens.Experimental Design: Human T cells expressing CAR targeting mesothelin or fibroblast activation protein and containing CD3ζ and 4–1BB cytoplasmic domains were intravenously injected into immunodeficient mice bearing large, established human mesothelin-expressing flank tumors. CAR TILs were isolated from tumors at various time points and evaluated for effector functions and status of inhibitory pathways.Results: CAR T cells were able to traffic into tumors with varying efficiency and proliferate. They were able to slow tumor growth, but did not cause regressions or cures. The CAR TILs underwent rapid loss of functional activity that limited their therapeutic efficacy. This hypofunction was reversible when the T cells were isolated away from the tumor. The cause of the hypofunction seemed to be multifactorial and was associated with upregulation of intrinsic T-cell inhibitory enzymes (diacylglycerol kinase and SHP-1) and the expression of surface inhibitory receptors (PD1, LAG3, TIM3, and 2B4).Conclusions: Advanced-generation human CAR T cells are reversibly inactivated within the solid tumor microenvironment of some tumors by multiple mechanisms. The model described here will be an important tool for testing T cell–based strategies or systemic approaches to overcome this tumor-induced inhibition. Our results suggest that PD1 pathway antagonism may augment human CAR T-cell function. Clin Cancer Res; 20(16); 4262–73. ©2014 AACR.

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PDF file - 756K, Supplemental Fig 1. EMP and EMMESO mesothelin expression. Supplemental Fig 2. EMMESO flank tumors retain antigen expression in vivo. Supplemental Fig 3. MesoCAR TILs are unable to secrete IL-2 in response to antigen. Supplemental Fig 4. Supplemental IL-2 helps but is not necessary for CAR TIL recovery. Supplemental Fig 5. IFNγ and TNFα secretion by CAR TILs recovers after resting away from tumor.

Altered neural crest cell (NCC) behaviour is an increasingly cited explanation for the domestication syndrome in animals. However, recent authors have questioned this explanation, while others cast doubt on whether domestication syndrome even exists. Here, we review published literature concerning this syndrome and the NCC hypothesis, together with recent critiques of both. We synthesize these contributions and propose a novel interpretation, arguing shared trait changes under ancient domestication resulted primarily from shared disruption of wild reproductive regimes. We detail four primary selective pathways for ‘reproductive disruption' under domestication and contrast these succinct and demonstrable mechanisms with cryptic genetic associations posited by the NCC hypothesis. In support of our perspective, we illustrate numerous important ways in which NCCs contribute to vertebrate reproductive phenotypes, and argue it is not surprising that features derived from these cells would be coincidentally altered under major selective regime changes, as occur in domestication. We then illustrate several pertinent examples of Darwin's ‘unconscious selection' in action, and compare applied selection and phenotypic responses in each case. Lastly, we explore the ramifications of reproductive disruption for wider evolutionary discourse, including links to wild ‘self-domestication' and ‘island effect’, and discuss outstanding questions.

Multiple myeloma (MM) shows constitutive activation of canonical and non-canonical nuclear factor-ĸB (NF-ĸB) signaling through genetic mutations or stimuli from the tumour microenvironment (TME). A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-ĸB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules IL-27 receptor-α (IL-27Rα) and the adhesion molecule JAM2 to be responsive to RELA at the mRNA and protein levels. IL-27Rα and JAM2 were expressed on primary MM cells at higher levels than on normal long-lived plasma cells (PCs) in the bone marrow. IL-27 activated STAT1, and to a lesser extent STAT3, in MM cell lines and in PCs generated from memory B-cells in an IL-21-dependent in vitro PC-differentiation assay. Concomitant activity of IL-21 and IL-27 enhanced differentiation into PCs and increased cell-surface expression of the known STAT target gene CD38. In accordance, a subset of MM cell lines and primary MM cells cultured with IL-27 upregulated CD38 cell-surface expression, a finding with potential implications for enhancing the efficacy of CD38-directed monoclonal antibody (mAb) therapies by increasing CD38-expression on tumour cells. The elevated expression of IL-27Rα and JAM2 on MM cells compared to normal PCs may be exploited for the development of targeted therapeutic strategies that modulate the interaction of MM cells with the TME.

INTRODUCTION: Existing automated seizure detection algorithms report sensitivities between 43% and 77% and specificities between 56% and 90%. The algorithms suffer from false alarms when applied to neonatal EEG because of the high degree of nurse handling and rhythmic patting used to soothe neonates. Computer vision technology that quantifies movement in real time could distinguish artifactual motion and improve automated neonatal seizure detection algorithms. METHODS: The authors used video EEG recordings from 43 neonates undergoing monitoring for seizures as part of the NEOLEV2 clinical trial. The Persyst neonatal automated seizure detection algorithm ran in real time during study EEG acquisitions. Computer vision algorithms were applied to extract detailed accounts of artifactual movement of the neonate or people near the neonate though dense optical flow estimation. RESULTS: Using the methods mentioned above, 197 periods of patting activity were identified and quantified, of which 45 generated false-positive automated seizure detection events. A binary patting detection algorithm was trained with a subset of 470 event videos. This supervised detection algorithm was applied to a testing subset of 187 event videos with 8 false-positive events, which resulted in a 24% reduction in false-positive automated seizure detections and a 50% reduction in false-positive events caused by neonatal care patting, while maintaining 11 of 12 true-positive seizure detection events. CONCLUSIONS: This work presents a novel approach to improving automated seizure detection algorithms used during neonatal video EEG monitoring. This artifact detection mechanism can improve the ability of a seizure detector algorithm to distinguish between artifact and true seizure activity.

A large number of heliophysicists from across career levels, institution types, and job titles came together to support a poster at Heliophysics 2050 and the position papers for the 2024 Heliophysics decadal survey titled “Cultivating a Culture of Inclusivity in Heliophysics,” “The Importance of Policies: It’s not just a pipeline problem,” and “Mentorship within Heliophysics.” While writing these position papers, the number of people who privately shared disturbing stories and experiences of bullying and harassment was shocking. The number of people who privately expressed how burned out they were was staggering. The number of people who privately spoke about how they considered leaving the field for their and their family’s health was astounding. And for as much good there is in our community, it is still a toxic environment for many. If we fail to do something now, our field will continue to suffer. While acknowledging the ongoing growth that we as individuals must work toward, we call on our colleagues to join us in working on organizational, group, and personal levels toward a truly inclusive culture, for the wellbeing of our colleagues and the success of our field. This work includes policies, processes, and commitments to promote: accountability for bad actors; financial security through removing the constant anxiety about funding; prioritization of mental health and community through removing constant deadlines and constant last-minute requests; a collaborative culture rather than a hyper-competitive one; and a community where people can thrive as whole persons and do not have to give up a healthy or well-rounded life to succeed.

Thoughtful, high-quality clinician–patient communication about starting antiretroviral therapy (ART) is a cornerstone of HIV care, and specific guidelines regarding exactly what ought to be discussed with patients considering ART have been in place since 2006. The extent to which the recommended topics are discussed and how these topics are addressed in observed dialogue in HIV care has not been studied. We conducted a content analysis to describe how these dialogues occur and, secondarily, assessed the frequency with which the recommended topics are discussed. Our study analyzed patient–clinician dialogue regarding ART initiation, comparing the content of 24 audio-recorded dialogues with the recommended guidelines, and describing how communication about the recommended topics takes place. While patient readiness to initiate therapy was discussed in the majority of visits (n = 18), the remaining topics (e.g. patient understanding of HIV and its treatment, motivation to adhere, barriers to and facilitators of adherence, social support, daily schedules, tolerance of pills) were discussed less often. Based on the findings, we suggest that systems be put in place (e.g. checklists) to guide providers in these discussions, and that providers utilize the teach-back method to ensure patient understanding.

The rectangular tetratopic linker, 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4TBAPy) along with rare-earth (RE) ions is used for the synthesis of 9 isostructures of a metal–organic framework (MOF) with shp topology, named RE-CU-10 (RE = Y(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III), Tm(III), Yb(III) and Lu(III)). The synthesis of each RE-CU-10 analogue requires different reaction conditions to achieve high quality phase pure products. Single crystal X-ray diffraction indicates the presence of a RE9-cluster in Y- to Tm-CU-10, while a unique RE11-cluster is observed for Yb- and Lu-CU-10. The photooxi-dation performance of the reported RE-CU-10 analogues is evaluated, giving insight into the competitive process of ligand-to-metal energy transfer versus the generation of singlet oxygen by RE-CU-10. The singlet oxygen produced is used to detoxify a mustard gas simulant 2-chloroethylethyl sulfide (2-CEES) to 2-chloroethyl ethyl sulfoxide (2-CEESO), with half-lives ranging from 4.0 to 5.8 min, some of the fastest reported to date using UV-irradiation and < 1 mol% catalyst, in methanol under O2 saturation.

BackgroundIn response to hypoxia, tumor cells undergo transcriptional reprogramming including upregulation of carbonic anhydrase (CA) IX, a metalloenzyme that maintains acid-base balance. CAIX overexpression has been shown to correlate with poor prognosis in various cancers, but the role of this CA isoform in hepatoblastoma (HB) has not been examined.MethodsWe surveyed the expression of CAIX in HB specimens and assessed the impact of SLC-0111, a CAIX inhibitor, on cultured HB cells in normoxic and hypoxic conditions.ResultsCAIX immunoreactivity was detected in 15 out of 21 archival pathology HB specimens. The CAIX-positive cells clustered in the middle of viable tumor tissue or next to necrotic areas. Tissue expression of CAIX mRNA was associated with metastasis and poor clinical outcome of HB. Hypoxia induced a striking upregulation of CAIX mRNA and protein in three HB cell models: the immortalized human HB cell line HUH6 and patient xenograft-derived lines HB-295 and HB-303. Administration of SLC-0111 abrogated the hypoxia-induced upregulation of CAIX and decreased HB cell viability, both in monolayer and spheroid cultures. In addition, SLC-0111 reduced HB cell motility in a wound healing assay. Transcriptomic changes triggered by SLC-0111 administration differed under normoxic vs. hypoxic conditions, although SLC-0111 elicited upregulation of several tumor suppressor genes under both conditions.ConclusionHypoxia induces CAIX expression in HB cells, and the CAIX inhibitor SLC-0111 has in vitro activity against these malignant cells.

ChatGPT, a language-learning model chatbot, has garnered considerable attention for its ability to respond to users’ questions. Using data from 14 countries and 186 institutions, we compare ChatGPT and student performance for 28,085 questions from accounting assessments and textbook test banks. As of January 2023, ChatGPT provides correct answers for 56.5 percent of questions and partially correct answers for an additional 9.4 percent of questions. When considering point values for questions, students significantly outperform ChatGPT with a 76.7 percent average on assessments compared to 47.5 percent for ChatGPT if no partial credit is awarded and 56.5 percent if partial credit is awarded. Still, ChatGPT performs better than the student average for 15.8 percent of assessments when we include partial credit. We provide evidence of how ChatGPT performs on different question types, accounting topics, class levels, open/closed assessments, and test bank questions. We also discuss implications for accounting education and research.

Coastalplain honeycombhead (Balduina angustifolia) is underutilised in ecosystem restoration and pollinator conservation projects. Seeds collected from different populations throughout Florida, USA during 2007 and 2016-2018 were used in experiments that evaluated the effects of a 0 or 12-hour photoperiod, seasonal and standard temperatures, 0-5,000 ppm gibberellic acid (GA) or source population (northwest, central and south Florida) on seed germination. For central Florida seeds, germination was high (62-74%) in all seasonal temperatures except for summer (4%) and was not affected by photoperiod. Germination differed for two northwest populations and was higher in warm (35/25 and 30/20°C) temperatures compared with cool (25/15 and 20/10°C) temperatures (63-72% vs. 9-36%). In a one-year move-along experiment, germination was similar at all seasonal and constant temperatures for seeds from central, south-central and south Florida, while northwest Florida seeds had reduced germination under winter temperatures. Germination of northwest Florida seeds after exposure to GA increased for two of four and three of four populations for one year and five-day old seeds, respectively. There were different temperature requirements on a regional scale and different dormancy levels at a local scale for coastalplain honeycombhead.

Pluripotent stem cells underpin a growing sector that leverages their differentiation potential for research, industry, and clinical applications. This review evaluates the landscape of methods in single-cell transcriptomics that are enabling accelerated discovery in stem cell science. We focus on strategies for scaling stem cell differentiation through multiplexed single-cell analyses, for evaluating molecular regulation of cell differentiation using new analysis algorithms, and methods for integration and projection analysis to classify and benchmark stem cell derivatives against in vivo cell types. By discussing the available methods, comparing their strengths, and illustrating strategies for developing integrated analysis pipelines, we provide user considerations to inform their implementation and interpretation.

Objective The use of benchtop metabolic profiling technology based on nuclear magnetic resonance (NMR) was evaluated in a small cohort of cats with a view to applying this as a viable and rapid metabolic tool to support clinical decision making. Results Urinary metabolites were analysed from four subjects consisting of two healthy controls and two chronic kidney disease (CKD) IRIS stage 2 cases. The study identified 15 metabolites in cats with CKD that were different from the controls. Among them were acetate, creatinine, citrate, taurine, glycine, serine and threonine. Benchtop NMR technology is capable of distinguishing between chronic kidney disease case and control samples in a pilot feline cohort based on metabolic profile. We offer perspectives on the further development of this pilot work and the potential of the technology, when combined with sample databases and computational intelligence techniques to offer a clinical decision support tool not only for cases of renal disease but other metabolic conditions in the future.

Measures of fluctuating asymmetry (FA) have been adopted widely as an estimate of developmental instability. Arising from various sources of stress, developmental instability is associated with an organism's capacity to maintain fitness. The process of domestication has been framed as an environmental stress with human-specified parameters, suggesting that FA may manifest to a larger degree among domesticates compared to their wild relatives. This study used three-dimensional geometric morphometric landmark data to (a) quantify the amount of FA in the cranium of six domestic mammal species and their wild relatives and, (b) provide novel assessment of the commonalities and differences across domestic/wild pairs concerning the extent to which random variation arising from the developmental system assimilates into within-population variation. The majority of domestic mammals showed greater disparity for asymmetric shape, however, only two forms (Pig, Dog) showed significantly higher disparity as well as a higher degree of asymmetry compared to their wild counterparts (Wild Boar, Wolf). Contra to predictions, most domestic and wild forms did not show a statistically significant correspondence between symmetric shape variation and FA, however, a moderate correlation value was recorded for most pairs (r-partial least squares >0.5). Within pairs, domestic and wild forms showed similar correlation magnitudes for the relationship between the asymmetric and symmetric components. In domesticates, new variation may therefore retain a general, conserved pattern in the gross structuring of the cranium, whilst also being a source for response to selection on specific features.

Vigorous or prolonged exercise poses a challenge to gastrointestinal system functioning and is associated with digestive symptoms. This narrative review addresses 1) the potential of dietary supplements to enhance gut function and reduce exercise-associated gastrointestinal symptoms and 2) strategies for reducing gastrointestinal-related side effects resulting from popular sports supplements. Several supplements, including probiotics, glutamine, and bovine colostrum, have been shown to reduce markers of gastrointestinal damage and permeability with exercise. Yet the clinical ramifications of these findings are uncertain, as improvements in symptoms have not been consistently observed. Among these supplements, probiotics modestly reduced exercise-associated gastrointestinal symptoms in a few studies, suggesting they are the most evidenced-based choice for athletes looking to manage such symptoms through supplementation. Carbohydrate, caffeine, and sodium bicarbonate are evidence-based supplements that can trigger gastrointestinal symptoms. Using glucose-fructose mixtures is beneficial when carbohydrate ingestion is high (>50 g/h) during exercise, and undertaking multiple gut training sessions prior to competition may also be helpful. Approaches for preventing caffeine-induced gastrointestinal disturbances include using low-to-moderate doses (

The consequences of poor breed management and inbreeding can range from gradual declines in individual productivity to more serious fertility and mortality concerns. However, many small and closed groups, as well as larger unmanaged populations, are plagued by genetic regression, often due to a dearth in breeding support tools which are accessible and easy to use in supporting decision‐making. To address this, we have developed a population management tool (BCAS, Breed Conservation and Management System) based on individual relatedness assessed using pedigree‐based kinship, which offers breeding recommendations for such populations. Moreover, we demonstrate the success of this tool in 16 years of employment in a closed equine population native to the UK, most notably, the rate of inbreeding reducing from more than 3% per generation, to less than 0.5%, or that attributed to genetic drift, as assessed over the last 16 years of implementation. Furthermore, with adherence to this program, the long‐term impact of poor management has been reversed and the genetic resource within the breed has grown from an effective population size of 20 in 1994 to more than 140 in 2020. The development and availability of our BCAS for breed management and selection establish a new paradigm for the successful maintenance of genetic resources in animal populations., Across the last 16 years, a genetic breed management program has led to the British population of the Cleveland Bay transitioning from an effective population size well below the UN FAO limit of concern of 50, to a stratified breeding system with N e now over 145.

We demonstrate a new approach to conducting a military force structure study under uncertainty. We apply the stochastic preemptive goal program approach, described by Ledwith et al., to balance probabilistic goals for military force effectiveness and the force’s cost. We use the Bayesian Enterprise Analytic Model (BEAM), as described in “Probabilistic Analysis of Complex Combat Scenarios,” to evaluate effectiveness, expressed in terms of the probability of achieving campaign objectives, in three hypothetical scenarios. We develop cost estimates along with their uncertainty to evaluate the force’s research and development, production, and annual operating and support costs. Our summary depicts how the trade-off between various prioritized goals influences the recommended robust force. Our approach enables defense leaders to balance risk in both force effectiveness in various scenarios along with risk in different types of cost categories.

Refereed/Peer-reviewed Potter, NJ, Tomkinson, GR, Dufner, TJ, Walch, TJ, Roemmich, JN, Wilson, PB, and Fitzgerald, JS. Effects of exercise training on resting testosterone concentrations in insufficiently active men: a systematic review and meta-analysis. J Strength Cond Res 35(12): 3521-3528, 2021-The anabolic hormone testosterone plays a pivotal role in the healthy aging of men and tends to decline with age. The aims of this systematic review and meta-analysis were 2-fold: (a) to evaluate the effect of exercise training on resting total testosterone concentration in insufficiently active, apparently healthy men and (b) to determine whether the effects of exercise training differed by training mode, age, body mass status, or testosterone measure. Electronic databases (MEDLINE, Scopus, CINAHL, and SPORTDiscus) were systematically searched (up to and including October 22, 2020) for peer-reviewed randomized controlled trials (RCTs) meeting the following criteria: population (insufficiently active, apparently healthy men aged ≥18 years), intervention (exercise training [any modality at intensity of ≥4 metabolic equivalents] lasting a minimum of 4 weeks), control (insufficiently active men), and outcome (resting total testosterone concentration). Intervention effects, weighted by the inverse of the pooled variance, were calculated relative to the control group as standardized mean differences (SMDs). Eleven RCTs, representing 421 insufficiently active, apparently healthy men aged 19-75 years across 16 intervention groups who participated in aerobic, resistance, or combined training lasting a median of 12 weeks, were included in the analysis. Overall, exercise training had a negligible effect on resting total testosterone concentration (mean SMD [95% CI]: 0.00 [-0.20 to 0.20]). Subgroup analyses indicated that the effect of exercise training was not significantly affected by training mode, age, body mass status, or testosterone measure. Exercise training does not seem to affect resting total or free testosterone concentration in insufficiently active, eugonadal men.

AMP-activated protein kinase (AMPK) plays a key role in the cellular response to low energy stress and has emerged as an attractive therapeutic target for tackling metabolic diseases. Whilst significant progress has been made regarding the physiological role of AMPK, its function in the kidney remains only partially understood. We use a mouse model expressing a constitutively active mutant of AMPK to investigate the effect of AMPK activation on kidney function in vivo. Kidney morphology and changes in gene and protein expression were monitored and serum and urine markers were measured to assess kidney function in vivo. Global AMPK activation resulted in an early-onset polycystic kidney phenotype, featuring collecting duct cysts and compromised renal function in adult mice. Mechanistically, the cystic kidneys had increased cAMP levels and ERK activation, increased hexokinase I (Hk I) expression, glycogen accumulation and altered expression of proteins associated with autophagy. Kidney tubule-specific activation of AMPK also resulted in a polycystic phenotype, demonstrating that renal tubular AMPK activation caused the cystogenesis. Importantly, human autosomal dominant polycystic kidney disease (ADPKD) kidney sections revealed similar protein localisation patterns to that observed in the murine cystic kidneys. Our findings show that early-onset chronic AMPK activation leads to a polycystic kidney phenotype, suggesting dysregulated AMPK signalling is a contributing factor in cystogenesis.

Campylobacter hepaticus is the aetiological agent of Spotty Liver Disease (SLD). SLD can cause significant production loss and mortalities among layer hens at and around peak of lay. We previously developed an enzyme linked immunosorbent assay (ELISA), SLD-ELISA1, to detect C. hepaticus specific antibodies from bird sera using C. hepaticus total proteins and sera pre-absorbed with Campylobacter jejuni proteins. The high specificity achieved with SLD-ELISA1 indicated the presence of C. hepaticus specific antibodies in sera of infected birds. However, some of the reagents used in SLD-ELISA1 are time consuming to prepare and difficult to quality control. This understanding led to the search for C. hepaticus specific immunogenic proteins that could be used in recombinant forms as antibody capture antigens in immunoassay design. In this study, an immunoproteomic approach that combined bioinformatics analysis, western blotting, and LC MS/MS protein profiling was used, and a fragment of filamentous hemagglutinin adhesin (FHA), FHA1,628−1,899 with C. hepaticus specific antigenicity was identified. Recombinant FHA1,628−1,899 was used as antigen coating on ELISA plates to capture FHA1,628−1,899 specific antibodies in sera of infected birds. SLD-ELISA2, based on the purified recombinant FHA fragment, is more user-friendly and standardizable than SLD-ELISA1 for screening antibody responses to C. hepaticus exposure in hens. This study is the first report of the use of FHA from a Campylobacter species in immunoassays, and it also opens future research directions to investigate the role of FHA in C. hepaticus pathogenesis and its effectiveness as a vaccine candidate.

Patient centered care (PCC) in human immunodeficiency virus (HIV) care systems in sub-Saharan Africa (SSA) may improve outcomes for persons with HIV (PWH). We review the progress the region has made in promoting PCC and highlight some of the implementation challenges and potential areas of research.Studies show growing interest in promoting PCC across HIV care programs in SSA. Effective implementation of PCC, however, is hampered by: (1) lack of consensus on the conceptualization of PCC, including definition, frameworks, measures, and implementation strategies; (2) limited regional studies on the adoption and sustainability of PCC interventions; and (3) healthcare structural challenges including limited capital and human resources, poor provider-patient dynamics, high provider turnover, and lack of continuity in care. Recent studies in the region have focused on identifying key PCC domains addressable in resource limited settings, understanding the PCC experiences and expectations of PWH and their providers, and testing innovative interventions. We highlight the need for additional studies to address the existing gaps.We discuss the progress and challenges of implementing PCC in HIV care settings in SSA as well as the need for additional research to ensure that proposed PCC interventions have optimal impact.

Sex differences in the lifetime risk and expression of disease are well-known. Preclinical research targeted at improving treatment, increasing health span, and reducing the financial burden of health care, has mostly been conducted on male animals and cells. The extent to which sex differences in phenotypic traits are explained by sex differences in body weight remains unclear. We quantify sex differences in the allometric relationship between trait value and body weight for 363 phenotypic traits in male and female mice, recorded in >2 million measurements from the International Mouse Phenotyping Consortium. We find sex differences in allometric parameters (slope, intercept, residual SD) are common (73% traits). Body weight differences do not explain all sex differences in trait values but scaling by weight may be useful for some traits. Our results show sex differences in phenotypic traits are trait-specific, promoting case-specific approaches to drug dosage scaled by body weight in mice.