Developing and Testing a Trafficability Index for Planting Corn and Cotton in the Texas Blackland Prairie

The Texas Blackland Prairie is one of the most productive agricultural regions in Texas. This region provides a long growing season coupled with soils that have a high water holding capacity. However, the soils also provide significant challenges to producers because the high water holding capacity is a product of a high clay percentage. This research was aimed to develop and test an expert-based trafficabililty index, based upon soil moisture, for planting cotton (Gossypium hirsutum L.) and corn (Zea mays L.) on the Texas Blackland Prairie. Testing the index focused on quantify the potential effect of high soil moisture at planting on seed furrow sidewall compaction and associated plant growth response. Once the trafficability index was developed, three workable soil moisture regimes were recreated in no-tillage and conventional tillage plots at the Stiles Farm Foundation in Thrall, Texas. The index nomenclature included: "Dry-Workable", "Optimal" and "Wet-Workable". After planting corn and cotton into conventional and no tillage plots, 0.45 x 0.20 x 0.15 m intact soil blocks were removed from each plot and kept in a controlled environment. At 28 days, each block was destructively harvested to quantify plant root and shoot growth responses. Each of the three soil moisture indexes was replicated thrice per crop, and the whole experiment was replicated twice in time, n = 48 blocks. The trafficability index was created using three producer experts, and over 10 interviews to collect a range in soil moisture samples. From "Wet Workable" to "Dry Workable", the gravimetric soil moistures were 0.17, 0.22, and 0.26 g g-1. For corn and cotton, a positive relationship between plant growth factors and planting at soil moisture existed. Plants planted at the highest soil moisture emerged faster and developed more root and shoot biomass than those planted at the lowest soil moisture. No evidence of a detrimental plant response because of seed furrow, sidewall compaction from planting at too high a soil moisture content could be quantified. Furthermore, the cotton plants in no-tillage performed better than in conventional tillage, but corn performed better in conventional tillage. Because the results showed an advantage to plant growth by planting in the "Wet Workable" index, the tillage practice that allows the producer to enter the field with a planter at higher moisture contents appears to have an advantage

HOOK-GRIP IMPROVES POWER CLEAN KINETICS AND KINEMATICS

The purpose of this study was to compare one repetition maximum (1RM), as well as biomechanical outputs across a range of loads (75-100%) in the power clean (PC) utilizing the hook grip (HG) or closed-grip (CG). Eleven well-trained males (PC 1RM=1.34xBW) with at least six months of HG experience volunteered. Following a familiarization session, PC 1RM testing with the HG and CG were completed in random order, 5-7 days apart on a force platform with linear position transducers and 2D motion capture. The HG condition resulted in greater PC 1RM (6.6%, ES=0.43), peak barbell velocity (2.9-5.2%, ES=0.41-0.70) and relative peak barbell power (5.7-15.1%, ES=0.32-0.71) at all submaximal loads compared to CG. No substantial differences were found in horizontal bar-path (ES=-0.27-0.32). The results of this study suggest that athletes who implement weightlifting movements in their physical preparation should adopt the HG

Frequency of HIV testing among gay and bisexual men in the UK: implications for HIV prevention

Objectives: The aim of the study was to explore HIV testing frequency among UK men who have sex with men (MSM) in order to direct intervention development. Methods: Cross-sectional surveys were completed by 2409 MSM in Edinburgh, Glasgow and London in 2011 and a Scotland-wide online survey was carried out in 2012/13. The frequency of HIV testing in the last 2 years was measured. Results: Overall, 21.2% of respondents reported at least four HIV tests and 33.7% reported two or three tests in the last 2 years, so we estimate that 54.9% test annually. Men reporting at least four HIV tests were younger and less likely to be surveyed in London. They were more likely to report higher numbers of sexual and anal intercourse partners, but not “higher risk” unprotected anal intercourse (UAI) with at least two partners, casual partners and/or unknown/discordant status partners in the previous 12 months. Only 26.7% (238 of 893) of men reporting higher risk UAI reported at least four tests. Among all testers (n = 2009), 56.7% tested as part of a regular sexual health check and 35.5% tested following a risk event. Differences were observed between surveys, and those testing in response to a risk event were more likely to report higher risk UAI. Conclusions: Guidelines recommend that all MSM test annually and those at “higher risk” test more frequently, but our findings suggest neither recommendation is being met. Additional efforts are required to increase testing frequency and harness the opportunities provided by biomedical HIV prevention. Regional, demographic and behavioural differences and variations in the risk profiles of testers suggest that it is unlikely that a “one size fits all” approach to increasing the frequency of testing will be successful

Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation

PURPOSE: Variants in MYBPC3 causing loss of function are the most common cause of hypertrophic cardiomyopathy (HCM). However, a substantial number of patients carry missense variants of uncertain significance (VUS) in MYBPC3. We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will identify a subgroup of HCM patients with a MYBPC3 VUS associated with increased clinical risk. METHODS: Among 7,963 patients in the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe), 120 unique missense VUS in MYBPC3 were identified. Variants were evaluated for their effect on subdomain folding and a stratified time-to-event analysis for an overall composite endpoint (first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation, and stroke) was performed for patients with HCM and a MYBPC3 missense VUS. RESULTS: We demonstrated that patients carrying a MYBPC3 VUS predicted to cause subdomain misfolding (STRUM+, ΔΔG ≤ −1.2 kcal/mol) exhibited a higher rate of adverse events compared with those with a STRUM- VUS (hazard ratio = 2.29, P = 0.0282). In silico saturation mutagenesis of MYBPC3 identified 4,943/23,427 (21%) missense variants that were predicted to cause subdomain misfolding. CONCLUSION: STRUM identifies patients with HCM and a MYBPC3 VUS who may be at higher clinical risk and provides supportive evidence for pathogenicity

Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients with Hypertrophic Cardiomyopathy

Background - Pathogenic variants in MYBPC3, encoding cardiac MyBP-C, are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique MYBPC3 variants and relatively small genotyped HCM cohorts have precluded detailed genotype-phenotype correlations. Methods - Patients with HCM and MYBPC3 variants were identified from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Variant types and locations were analyzed, morphologic severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, LVAD/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro. Results - Among 4,756 genotyped HCM patients in SHaRe, 1,316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or non-truncating (N=22 unique variants, 191 patients) variants in MYBPC3. Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5' - 3' quartiles or by founder variant subgroup). Non-truncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, p<0.001 vs. gnomAD common variants) and were associated with similar hypertrophy severity and adverse event rates as observed with truncating variants. MyBP-C with variants in the C3, C6, and C10 domains was expressed in rat ventricular myocytes. C10 mutant MyBP-C failed to incorporate into myofilaments and degradation rates were accelerated by ~90%, while C3 and C6 mutant MyBP-C incorporated normally with degradation rate similar to wild-type. Conclusions - Truncating variants account for 91% of MYBPC3 pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Non-truncating MYBPC3 pathogenic variants are regionally clustered, and a subset also cause loss-of-function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating vs. non-truncating variants

Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry

Background: The term "end stage" has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is <50%. The prognosis of HCM-LVSD has reportedly been poor, but because of its relative rarity, the natural history remains incompletely characterized. Methods: Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. Results: From a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3-13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7-3.5]), and left ventricular ejection fraction <35% (HR, 2.0 [95% CI, 1.3-2.8]). The incidence of new HCM-LVSD was ≈7.5% over 15 years. Significant predictors of developing incident HCM-LVSD included greater left ventricular cavity size (HR, 1.1 [95% CI, 1.0-1.3] and wall thickness (HR, 1.3 [95% CI, 1.1-1.4]), left ventricular ejection fraction of 50% to 60% (HR, 1.8 [95% CI, 1.2, 2.8]-2.8 [95% CI, 1.8-4.2]) at baseline evaluation, the presence of late gadolinium enhancement on cardiac magnetic resonance imaging (HR, 2.3 [95% CI, 1.0-4.9]), and the presence of a pathogenic/likely pathogenic sarcomeric variant, particularly in thin filament genes (HR, 1.5 [95% CI, 1.0-2.1] and 2.5 [95% CI, 1.2-5.1], respectively). Conclusions: HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants)

Left Ventricular Systolic Dysfunction in Patients Diagnosed with Hypertrophic Cardiomyopathy during Childhood:Insights from the SHaRe Registry

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS:Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction &lt;50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (&lt;18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age &lt;12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction &lt;35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.</p