UNASSIGNED: Current guidelines recommend simultaneous initiation of multidrug guideline-directed medical therapy classes for heart failure with reduced ejection fraction.
UNASSIGNED: The purpose of this study was to evaluate county-level variation in use of triple guideline-directed medical therapy, defined as simultaneous prescription fills for beta-blockers, renin-angiotensin system inhibitors or angiotensin receptor neprilysin inhibitors, and mineralocorticoid receptor antagonists, in heart failure with reduced ejection fraction.
UNASSIGNED: We conducted a cohort study using Medicare Fee-for-Service claims data (parts A, B, and D between 2013 and 2019). Features of counties including area-level indicators of poverty, employment, and educational attainment and aggregated patient-level sociodemographic and medical history variables were compared by quintiles of triple therapy use. A multilevel logistic regression model was constructed to estimate the contextual effect of clustering by counties, which was expressed as a median OR.
UNASSIGNED: 304,857 patients from 2,600 counties (83% of all U.S. counties) were included. The median for triple therapy use was 14.3% (IQR: 10.3%-18.8%) across included counties with a wide variation (range: 0%-54.5%). Compared to counties in the highest use quintile, counties in lowest triple therapy use quintile had worse area-level indicators of socioeconomic status (% unemployment 6.8% vs 6.2%). Counties in lowest quintile had higher proportion of Black patients (13.3% vs 5.7% in highest quintile) and patients with low-income subsidy (29.3% vs 25.8% in highest quintile). The median OR was 1.30 (95% CI: 1.28-1.33).
UNASSIGNED: We observed variation in triple therapy use across counties in the United States with suboptimal local use patterns correlating with indicators of socioeconomic disadvantage.

Much historic work has focused on establishing geographical and ecological rules that broadly explain patterns in size variation. We examined geographic variation in Spotted Hyena skull size using geometric morphometrics and spatial statistics. We quantified size variation and sexual size dimorphism of the skull, and evaluated the influence of temperature, precipitation, land cover type, and population density on skull size. We found that female spotted hyenas are slightly larger on average than males. Our analysis of regional differences did not indicate geographic variation in sexual size dimorphism. Skull size of Spotted Hyenas varies with geography but does not adhere to Bergmann\'s Rule. The smallest individuals of both sexes occur between -5.00° and 10.00° latitude and east of 28.50° longitude, with larger individuals being found elsewhere. Although Spotted Hyena skull size co-varies in some views with such variables as habitat type and climate indicators, skull size in this species most strongly co-varies with population density. The highest population densities are associated with the smallest skull size, possibly reflecting a relationship between high population density and access to resources. These results suggest that geographic variation in Spotted Hyena skull size is better explained by the energetic equivalence rule than Bergmann\'s Rule.

OBJECTIVE: Compared to heart failure (HF) with reduced ejection fraction, HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) are increasing in prevalence, yet little is known about the geographic variation in patient characteristics, treatments and outcomes among these two HF phenotypes. The aim of this study was to investigate geographic differences in HFpEF and HFmrEF.
RESULTS: We conducted an individual patient analysis of five clinical trials enrolling patients with HFpEF or HFmrEF from North America (NA), Latin America (LA), Western Europe (WE), Central/Eastern Europe and Russia (CEER), and Asia-Pacific (AP). We compared regions using descriptive statistics and multivariable regression models. Among the 19 959 patients included, 4066 (23.1%) had HFmrEF and 15 353 (76.9%) HFpEF. Regardless of HF phenotype, patients from WE were oldest, and those in CEER youngest. LA had the largest portion of females and NA most black patients. Obesity and diabetes were most prevalent in NA and hypertension and coronary heart disease most common in CEER. Self-reported health status varied strikingly and was the worst in NA and best in AP. Among patients with HFmrEF, rates of the primary composite endpoint (cardiovascular death or HF hospitalization) were: NA 12.56 per 100 patient-years (/100py), AP 11.67/100py, CEER 10.12/100py, LA 8.90/100py, and WE 8.43/100py, driven by differences in the rate of HF hospitalization. The corresponding values in HFpEF were 11.47/100py, 7.80/100py, 5.47/100py, 5.92/100py, and 7.80/100py, respectively.
CONCLUSIONS: There is substantial geographic variation in patient characteristics, treatment and outcomes among patients with HFpEF and HFmrEF. These findings have implications for interpretation and generalizability of trial results, design and conduct of future trials, and optimization of care for these patients.

The geographical variation and domestication of tree species are an important part of the theory of forest introduction, and the tracing of the germplasm is the theoretical basis for the establishment of high-quality plantations. Chinese pine (Pinus tabuliformis Carr.) is an important native timber tree species widely distributed in northern China, but it is unclear exactly where germplasm of the main Chinese pine plantation populations originated. Here, using two mtDNA markers, we analyzed 796 individuals representing 35 populations (matR marker), and 873 individuals representing 38 populations (nad5-1 marker) of the major natural and artificial populations in northern China, respectively (Shanxi, Hebei and Liaoning provinces). The results confirmed that the core position of natural SX* populations (\"*\" means natural population) in the Chinese pine populations of northern China, the genetic diversity of HB and LN plantations was higher than that of natural SX* populations, and there was a large difference in genetic background within the groups of SX* and LN, HB showed the opposite. More importantly, we completed the \"point by point\" tracing of the HB and LN plantings. The results indicated that almost all HB populations originated from SX* (GDS*, ZTS*, GCS*, and THS*), which resulted in homogeneity of the genetic background of HB populations. Most of germplasm of the LN plantations originated from LN* (ZJS* and WF*), and the other part originated from GDS* (SX*), resulting in the large differences in the genetic background within the LN group. Our results provided a reliable theoretical basis for the scientific allocation, management, and utilization of Chinese pine populations in northern China, and for promoting the high-quality establishment of Chinese pine plantations.

Spatial variation in parasitic infection may have many physical and biological drivers. Uncovering these drivers may be especially important for parasites of ecosystem engineers because the engineers are foundational to their communities. Oysters are an important coastal ecosystem engineer that have declined drastically worldwide, in part due to enhanced cases of lethal oyster diseases, such as Dermo and MSX, caused by the protozoan parasites Perkinsus marinus and Haplosporidium nelsoni, respectively. Besides water quality and hydrodynamics, there is little information on how other variables influence the prevalence and intensity of these pathogens in oysters across a regional scale. To examine drivers of spatial variation in these oyster parasites-including host size, local reef properties, and landscape properties-we sampled 24 reefs systematically spread along the coast of Georgia, USA. Across sites, we found universally high prevalence of oysters with at least one of these parasites (91.02% ± 8.89, mean ± SD). Not only are high levels of parasite prevalence potentially problematic for a pivotal ecosystem engineer, but also low spatial variability may limit the explanatory power of variables across a regional scale. Our statistical models explained between 18 and 42% of the variation in spatial patterns of prevalence and intensity of these microparasites. Interestingly, landscape context was a positive predictor of P. marinus, but a negative predictor of H. nelsoni. Overall, our findings suggest that factors driving parasite prevalence and intensity operate across multiple spatial scales, and the same factor can both facilitate and hinder different parasites within the same host species.

Social bees have evolved sophisticated communication systems to recruit nestmates to newly found food sources. As foraging ranges can vary from a few hundred meters to several kilometers depending on the environment or season, populations of social bee species living in different climate zones likely show specific adaptations in their recruitment communication. Accordingly, studies in the western honey bee, Apis mellifera, demonstrated that temperate populations exhibit shallower dance-calibration curves compared with tropical populations. Here, we report the first comparison of calibration curves for three Indian Apis cerana lineages: the tropical Apis indica, and the two montane Himalayan populations Apis cerana cerana (Himachal Pradesh) and Apis cerana kashmirensis (Jammu and Kashmir). We found that the colonies of the two montane A. cerana populations show dance-distance calibration curves with significantly shallower slopes than those of the tropical A. indica. Next, we transferred A. c. cerana colonies to Bangalore (∼ 2600 km away) to obtain calibration curves in the same location as A. indica. The common garden experiment confirmed this difference in slopes, implying that the lineages exhibit genetically fixed differences in dance-distance coding. However, the slopes of the calibration curves of the transferred A. c. cerana colonies were also significantly higher than those of the colonies tested in their original habitat, indicating an important effect of the environment. The differences in dance-distance coding between temperate and tropical A. cerana lineages resemble those described for Apis mellifera, suggesting that populations of both species independently evolved similar adaptations.

Phenotypic plasticity, the ability of a single genotype to produce different phenotypes under different environmental conditions, plays a profound role in several areas of evolutionary biology. One important role is as an adaptation to a variable environment. While plasticity is extremely well documented in response to many environmental factors, there is controversy over how much of that plasticity is adaptive. Evidence is also mixed over how often conspecific populations display qualitative differences in the nature of plasticity. We present data on the reaction norms of growth and maturation to variation in temperature and salinity in male and female sailfin mollies (Poecilia latipinna) from three locally adjacent populations from South Carolina (SC). We compare these reaction norms to those previously reported in locally adjacent populations from north Florida (NF). In general, patterns of plasticity in fish from SC were similar to those in fish from NF. The magnitude of plasticity differed; fish from SC displayed less plasticity than fish from NF. This was because SC fish grew faster and matured earlier at the lower temperatures and salinities compared to NF fish. This is a countergradient pattern of variation, in which SC fish grew faster and matured earlier in conditions that would otherwise slow growth and delay maturity. Among fish from both regions, males were much less plastic than females, especially for length at maturity. While there was no detectable heterogeneity among populations from NF, males from one of the SC populations, which is furthest from the other two, displayed a qualitatively different response in age at maturity to temperature variation than did males from the other two SC populations. The pattern of population variation in plasticity within and among regions suggests that gene flow, which diminishes with distance in sailfin mollies, plays a critical role in constraining divergence in norms of reaction.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and cardio-renal outcomes for people with type 2 diabetes (T2D). However, geographic and socio-economic variation in use is not well understood.
METHODS: We identified 367 829 New South Wales residents aged ≥40 years who dispensed metformin in 2020 as a proxy for T2D. We estimated the prevalence of use of other glucose-lowering medicines among people with T2D and the prevalence of SGLT2i and GLP-1RA use among people using concomitant T2D therapy (i.e. metformin + another glucose-lowering medicine). We measured the prevalence by small-level geography, stratified by age group, and characterized by remoteness and socio-economic status.
RESULTS: The prevalence of SGLT2i (29.7%) and GLP-1RA (8.3%) use in people with T2D aged 40-64 increased with geographic remoteness and in areas of greater socio-economic disadvantage, similar to other glucose-lowering medicines. The prevalence of SGLT2i (55.4%) and GLP-1RA (15.4%) among people using concomitant T2D therapy varied across geographic areas, with lower SGLT2i use in more disadvantaged areas and localized areas of high GLP-1RA use (2.5 times the median). Compared with people aged 40-64 years, the prevalence of SGLT2i and GLP-1RA use was lower in older age groups, but with similar patterns of variation across geographic areas.
CONCLUSIONS: The prevalence of SGLT2i and GLP-1RA use varied by geography, probably reflecting a combination of system- and prescriber-level factors. Socio-economic variation in GLP-1RA use was overshadowed by localized patterns of prescribing. Continued monitoring of variation can help shape interventions to optimize use among people who would benefit the most.

UNASSIGNED: Seed traits related to recruitment directly affect plant fitness and persistence. Understanding the key patterns and influencing factors of seed trait variations is conducive to assessing plant colonization and habitat selection. However, the variation patterns of the critical seed traits of shrub species are usually underrepresented and disregarded despite their vital role in alpine desert ecosystems.
UNASSIGNED: This study gathered seeds from 21 Asterothamnus centraliasiaticus populations across the Qinghai-Tibetan Plateau, analyzing geographical patterns of seed traits to identify external environmental influences. Additionally, it explored how seed morphology and nutrients affect germination stress tolerance, elucidating direct and indirect factors shaping seed trait variations.
UNASSIGNED: The results present substantial intraspecific variations in the seed traits of A. centraliasiaticus. Seed traits except seed length-to-width ratio (LWR) all vary significantly with geographic gradients. In addition, the direct and indirect effects of climatic variables and soil nutrients on seed traits were verified in this study. Climate mainly influences seed nutrients, and soil nutrients significantly affect seed morphology and seed nutrients. Furthermore, climate directly impacts seed germination drought tolerance index (GDTI) and germination saline-alkali tolerance index (GSTI). Seed germination cold tolerance index (GCTI) is influenced by climate and soil nutrients (mostly SOC). GDTI and GSTI are prominently influenced by seed morphology (largely the seed thousand-grain weight (TGW)), and GCTI is evidently affected by seed nutrients (mainly the content of soluble protein (CSP)).
UNASSIGNED: The findings of this study amply explain seed trait variation patterns of shrubs in alpine desert ecosystems, possessing significant importance for understanding the mechanism of shrub adaptation to alpine desert ecosystems, predicting the outcomes of environmental change, and informing conservation efforts. This study can be a valuable reference for managing alpine desert ecosystems on the Qinghai-Tibetan Plateau.

While time spent practicing inpatient dermatology has decreased since the 1990s, less is known about the current state of inpatient dermatology. We describe the distribution and frequency of inpatient dermatology encounters servicing the United States Medicare population between 2013 and 2019. Cross-sectional analysis of publicly available inpatient Medicare Part B claims data from 2013 to 2019 was conducted. Main outcomes and measures were characteristics and trends of dermatologists performing inpatient encounters. Categorical variables were compared using χ2 analysis. Trends were analyzed for linearity using Pearson correlation coefficient. 782 physicians met inclusion criteria for inclusion. Dermatologists were more often male (56.5%), possessing allopathic Medical Doctorate (MD) (86.3%), and in metropolitan settings (98.2%). However, proportion of female inpatient dermatologists increased significantly (37.9% to 46.2%). Across rural and metropolitan practices, number of inpatient physicians (2013: 356; 2019: 281) and number of medical centers in which dermatology encounters occurred (2013: 239; 2019: 157) decreased, more significantly in non-residency-associated institutions. Spatial analysis revealed wide regions lacking dermatologists meeting defined criteria. Limitations included the need for ten Medicare inpatient encounters for inclusion, counties without reported data. In conclusion, the number of dermatologists performing > 10 inpatient encounters per year is decreasing, and large variations exist in the number of U.S. inpatient dermatology visits.