Effects of Lean Beef Supplementation on Iron Status, Body Composition and Performance of Collegiate Distance Runners

Iron deficiency is prevalent among endurance athletes, particularly females. Low iron may compromise oxygen delivery and physical performance. Vegetarianism, desire for convenience, and perceived health risks associated with red meat contribute to low bioavailable iron intakes. The purpose of this study was to examine if lean beef supplementation would maintain iron status, improve body composition and increase performance of distance runners after 8 weeks. Twenty-eight (14 female) Division-I cross-country runners were stratified by iron status, use of iron supplements, and gender, and randomized into a control (n = 14) and intervention group. All participants maintained their typical diet and consumed a daily multivitamin, while the intervention group consumed 9 ounces of lean beef weekly. Dietary intake (total iron, heme-iron, protein, zinc), body composition, VO2max, and iron status (hemoglobin, hematocrit, serum iron, serum ferritin, total iron binding capacity [TIBC]) were measured at baseline and post-intervention. The intervention group had greater intakes of total and heme-iron. There were no group differences in amino acids, protein, or calories. Both groups had a significant body fat increase and lean mass decease over time. There was a significant VO2max in- crease over time in both groups. There were no group differences due to the intervention in serum ferritin, hemoglobin, serum iron, and TIBC. There was a significant difference in hematocrit between groups as a result of the intervention. In conclusion, increasing bioavailable iron from red meat may have effects on body composition and maintenance of blood iron markers; however, its direct impact on performance among endurance athletes is unclear

The Association between Mediated Deprivation and Ovarian Cancer Survival among African American Women

BACKGROUND: Deprivation indices are often used to adjust for socio-economic disparities in health studies. Their role has been partially evaluated for certain population-level cancer outcomes, but examination of their role in ovarian cancer is limited. In this study, we evaluated a range of well-recognized deprivation indices in relation to cancer survival in a cohort of self-identified Black women diagnosed with ovarian cancer. This study aimed to determine if clinical or diagnostic characteristics lie on a mediating pathway between socioeconomic status (SES) and deprivation and ovarian cancer survival in a minority population that experiences worse survival from ovarian cancer. METHODS: We used mediation analysis to look at the direct and indirect causal effects of deprivation indices with main mediators of the SEER stage at diagnosis and residual disease. The analysis employed Bayesian structural equation models with variable selection. We applied a joint Bayesian structural model for the mediator, including a Weibull mixed model for the vital outcome with deprivation as exposure. We selected modifiers via a Monte Carlo model selection procedure. RESULTS: The results suggest that high SES-related indices, such as Yost, Kolak urbanicity (URB), mobility (MOB) and SES dimensions, and concentrated disadvantage index (CDI), all have a significant impact on improved survival. In contrast, area deprivation index (ADI)/Singh, and area level poverty (POV) did not have a major impact. In some cases, the indirect effects have very wide credible intervals, so the total effect is not well estimated despite the estimation of the direct effect. CONCLUSIONS: First, it is clear that commonly used indices such as Yost, or CDI both significantly impact the survival experience of Black women diagnosed with epithelial ovarian cancer. In addition, the Kolak dimension indices (URB, MOB, mixed immigrant: MICA and SES) also demonstrate a significant association, depending on the mediator. Mediation effects differ according to the mediator chosen

GAWMerge expands GWAS sample size and diversity by combining array-based genotyping and whole-genome sequencing

Genome-wide association studies (GWAS) have made impactful discoveries for complex diseases, often by amassing very large sample sizes. Yet, GWAS of many diseases remain underpowered, especially for non-European ancestries. One cost-effective approach to increase sample size is to combine existing cohorts, which may have limited sample size or be case-only, with public controls, but this approach is limited by the need for a large overlap in variants across genotyping arrays and the scarcity of non-European controls. We developed and validated a protocol, Genotyping Array-WGS Merge (GAWMerge), for combining genotypes from arrays and whole-genome sequencing, ensuring complete variant overlap, and allowing for diverse samples like Trans-Omics for Precision Medicine to be used. Our protocol involves phasing, imputation, and filtering. We illustrated its ability to control technology driven artifacts and type-I error, as well as recover known disease-associated signals across technologies, independent datasets, and ancestries in smoking-related cohorts. GAWMerge enables genetic studies to leverage existing cohorts to validly increase sample size and enhance discovery for understudied traits and ancestries

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

A Pharmacist-Led, Same-Day, HIV Pre-Exposure Prophylaxis Initiation Program to Increase PrEP Uptake and Decrease Time to PrEP Initiation

Mississippi has one of the highest rates of HIV in the United States, but has low pre-exposure prophylaxis (PrEP) uptake, particularly among black men who have sex with men (MSM) and women. From November 2018 to May 2019, patients at high risk of HIV who tested negative for HIV at a nonclinical testing center in Jackson, Mississippi, were referred to an on-site clinical pharmacist for same-day PrEP initiation. The pharmacist evaluated patients for medical contraindications to PrEP, but no baseline labs were obtained. The pharmacist provided a PrEP prescription and scheduled a clinical appointment for patients within 6 weeks, at which time they were evaluated by a clinician and completed baseline labs. The pharmacist evaluated 69 patients for PrEP; 57% were MSM, 77% were black, and 65% were uninsured. All patients received a PrEP prescription; 83% received the prescription the same day and 97% received it within 5 days. Fifty-three (77%) of 69 clients filled the prescription; 87% of whom filled it within 1 week. Only 23 (43%) of 53 clients who filled their prescription attended their initial clinical appointment within 6 weeks of obtaining PrEP. There were no differences in PrEP initiation or retention by patient sex/gender. This pilot program suggests that an on-site pharmacist working in a nonclinical testing center in the southern United States can successfully initiate PrEP among predominately low-income black MSM. Future efforts should seek to better integrate laboratory testing into this demedicalized model of PrEP and to improve retention in care

Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion

Retinal vein occlusion can cause blindness, and features neuronal dysfunction, inflammation and breakdown of vascular integrity. Here the authors report a non-apoptotic role of endothelial caspase-9 in regulating blood-retina barrier integrity and neuronal survival, which can be therapeutically targeted in a mouse model of retinal vein occlusion

Author Correction: Endothelial activation of caspase-9 promotes neurovascular injury in retinal vein occlusion

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

Modeling morphological learning, typology, and change : What can the neural sequence-to-sequence framework contribute?

We survey research using neural sequence-to-sequence models as computational models of morphological learning and learnability. We discuss their use in determining the predictability of inflectional exponents, in making predictions about language acquisition and in modeling language change. Finally, we make some proposals for future work in these areas