The Role of the Flexor Hallucis Longus in the Treatment of the Painful Hallux Metatarsophalangeal Joint.

BACKGROUND: Pain in the hallux metatarsophalangeal joint (MTPJ) is very common, yet the underlying etiology remains unknown. Previous clinical research and biomechanical research has implicated stenosing flexor hallucis longus (FHL) tendonitis as a possible cause. The hypothesis of this study was that treatment solely focusing on alleviating restricted FHL excursion would be beneficial in patients with hallux MTPJ pain. METHODS: This is a retrospective study of those treated in the Foot & Ankle Division between January 2009, and December 2018, who were diagnosed with FHL tendonitis with associated pain in the hallux MTPJ. Demographics, comorbidities, examination findings, imaging results, pain scores, treatment instituted, and outcome was obtained from the electronic medical record. The primary outcome was the improvement in the pain score (visual analog scale [VAS]). The surgical patients were included if their procedure was solely related to the FHL (posteromedial ankle release ± os trigonum resection). The decision to have surgery was analyzed by univariate and multivariable statistics using demographics, comorbidities, and clinical findings as potential factors (P < .05). RESULTS: In 75% (59 of 79 feet), nonoperative treatment of FHL stenosis resulted in a decrease in pain scores that the patients felt was satisfactory. The operative group that had an FHL release showed decreased pain in 90% (18 of 20 feet). Multivariable analysis identified the need for immobilization (OR 9.8, 95% CI 1.8-55.2, P = .009), participating in athletics (OR 8.7, 95% CI 1.8-42.2, P = .007), and higher initial VAS (OR 1.7, 95% CI 1.3-2.3, P < .001) as being associated with the decision for surgery. CONCLUSION: Previous biomechanical studies have suggested that stenosing FHL synovitis can cause increased intraarticular loading in the hallux MTPJ. The current clinical study supports this hypothesis, demonstrating that treatment focused on relieving restricted FHL excursion can ameliorate pain in the hallux MTPJ in select cases.

Using heart rate and acceleration biologgers to estimate winter activity costs in free-swimming largemouth bass.

Winter is a critical period for largemouth bass (Micropterus nigricans) with winter severity and duration limiting their population growth at northern latitudes. Unfortunately, we have an incomplete understanding of their winter behaviour and energy use in the wild. More winter-focused research is needed to better understand their annual energy budget, improve bioenergetics models, and establish baselines to assess the impacts of climate warming; however, winter research is challenging due to ice cover. Implantable tags show promise for winter-focused research as they can be deployed prior to ice formation. Here, using swim tunnel respirometry, we calibrated heart rate and acceleration biologgers to enable estimations of metabolic rate (MO2) and swimming speed in free-swimming largemouth bass across a range of winter-relevant temperatures. In addition, we assessed their aerobic and swim performance. Calculated group thermal sensitivities of most performance metrics indicated the passive physicochemical effects of temperature, suggesting little compensation in the cold; however, resting metabolic rate and critical swimming speed showed partial compensation. We found strong relationships between acceleration and swimming speed, as well as between MO2 and heart rate, acceleration, or swimming speed. Jackknife validations indicated that these modeled relationships accurately estimate swimming speed and MO2 from biologger recordings. However, there were relatively few reliable heart rate recordings to model the MO2 relationship. Recordings of heart rate were high-quality during holding but dropped during experimentation, potentially due to interference from aerobic muscles during swimming. The models informed by acceleration or swimming speed appear to be best suited for field applications.

Genetic diversity of United States Rambouillet, Katahdin and Dorper sheep.

BACKGROUND: Managing genetic diversity is critically important for maintaining species fitness. Excessive homozygosity caused by the loss of genetic diversity can have detrimental effects on the reproduction and production performance of a breed. Analysis of genetic diversity can facilitate the identification of signatures of selection which may contribute to the specific characteristics regarding the health, production and physical appearance of a breed or population. In this study, breeds with well-characterized traits such as fine wool production (Rambouillet, N = 745), parasite resistance (Katahdin, N = 581) and environmental hardiness (Dorper, N = 265) were evaluated for inbreeding, effective population size (Ne), runs of homozygosity (ROH) and Wright's fixation index (FST) outlier approach to identify differential signatures of selection at 36,113 autosomal single nucleotide polymorphisms (SNPs). RESULTS: Katahdin sheep had the largest current Ne at the most recent generation estimated with both the GONe and NeEstimator software. The most highly conserved ROH Island was identified in Rambouillet with a signature of selection on chromosome 6 containing 202 SNPs called in an ROH in 50 to 94% of the individuals. This region contained the DCAF16, LCORL and NCAPG genes that have been previously reported to be under selection and have biological roles related to milk production and growth traits. The outlier regions identified through the FST comparisons of Katahdin with Rambouillet and Dorper contained genes with known roles in milk production and mastitis resistance or susceptibility, and the FST comparisons of Rambouillet with Katahdin and Dorper identified genes related to wool growth, suggesting these traits have been under natural or artificial selection pressure in these populations. Genes involved in the cytokine-cytokine receptor interaction pathways were identified in all FST breed comparisons, which indicates the presence of allelic diversity between these breeds in genomic regions controlling cytokine signaling mechanisms. CONCLUSIONS: In this paper, we describe signatures of selection within diverse and economically important U.S. sheep breeds. The genes contained within these signatures are proposed for further study to understand their relevance to biological traits and improve understanding of breed diversity.

Internal and external spatial analysis of trace elements in local crayfish.

Pollution in urban environments is a major health concern for humans as well as the local wildlife and aquatic species. Anthropogenic waste and discharge from storm drainage accumulate nutrients and environmental contaminants in local water systems. Locating contaminated sites using water samples over the vast landscape is a daunting task. Crayfish thrive in urban environments and have been used for biomonitoring pollutants. This study aimed to use crayfish as sentinels to monitor for elements in local environments. In this study, crayfish were used to measure metals and metalloids in lotic environments using ICP-OES analysis of abdominal and exoskeletal tissue. Using cluster analysis, geographical zones of trace element accumulation were determined. Eighteen total elements were analysed providing baseline data on local genera, biometric data, and element concentrations averaging 267.3 mg/kg Mn in the exoskeleton and with Zn averaging 6.88 mg/kg being significantly higher in the abdomen. Correlations of elements with biometric data allowed for internal analyses of elements. The elements As, Cr, Hg, Ni, and Tl demonstrated equivalent concentrations in both tissues. The crayfish locations with high abundance of elements allowed for the determination of contaminated areas with higher accumulations being areas of active urban development. These analyses gave measurable results of metal and metalloid to pinpoint potential sources of pollutants. Since crayfish are consumed globally as a food source, these methods can be used to determine the risk of toxic metals being passed through the food chain to the public.

Assessing the safety of bladder-preserving therapy as an alternative to surgical intervention in elderly patients with muscle invasive bladder cancer.

BACKGROUND: There is interest in using bladder-preserving therapy as an alternative definitive therapy for muscle invasive bladder cancer in certain high-risk groups such as the elderly. OBJECTIVE: To determine if bladder-preserving therapy represents a safer alternative to surgical intervention in elderly patients with muscle invasive bladder cancer. METHODS: We surveyed the Surveillance, Epidemiology and End Results database (SEER) for cases of non-metastasized malignant bladder cancer in patients aged 80+. Survival outcomes with radical cystectomy (RC) with or without chemotherapy were compared to those after chemotherapy and radiation without cystectomy. We performed log-rank tests and Kaplan-Meier and cox regression and hazard analyses before and after propensity score matching. RESULTS: A total of 2995 patients were identified, with 49.98% treated with RC only, 8.65% treated with RC/chemotherapy, and 41.37% treated with chemotherapy and radiation without RC. Median overall survival for the RC only, RC/chemotherapy and chemotherapy/radiation groups were 31.4, 44.1, and 24.6 months, respectively. On multivariate analysis, hazard ratios (reference: RC/chemotherapy group) were RC Only (HR = 1.408 (95% CI 1.188-1.669), p < 0.0001) and chemotherapy/radiation (HR = 1.650 (95% CI 1.390-1.959), p < 0.0001). After matching the chemotherapy/radiation and RC/chemotherapy groups, the former continued to show survival hazard (HR = 1.744 (95% CI 1.414-2.155), p < 0.0001). CONCLUSIONS: Octogenarians should be offered definitive local therapy for their localized bladder cancer including RC and chemotherapy. Bladder-sparing alternatives should be reserved for patients unfit for surgery.

Identification of distinct and shared biomarker panels in different manifestations of cerebral small vessel disease through proteomic profiling.

The pathophysiology underlying various manifestations of cerebral small vessel disease (cSVD) remains obscure. Using cerebrospinal fluid proximity extension assays and co-expression network analysis of 2,943 proteins, we found common and distinct proteomic signatures between white matter lesions (WML), microbleeds and infarcts measured in 856 living patients, and validated WML-associated proteins in three additional datasets. Proteins indicative of extracellular matrix dysregulation and vascular remodeling, including ELN, POSTN, CCN2 and MMP12 were elevated across all cSVD manifestations, with MMP12 emerging as an early cSVD indicator. cSVD-associated proteins formed a co-abundance network linked to metabolism and enriched in endothelial and arterial smooth muscle cells, showing elevated levels at early disease manifestations. Later disease stages involved changes in microglial proteins, associated with longitudinal WML progression, and changes in neuronal proteins mediating WML-associated cognitive decline. These findings provide an atlas of novel cSVD biomarkers and a promising roadmap for the next generation of cSVD therapeutics.

A model for accurate quantification of CRISPR effects in pooled FACS screens.

CRISPR screens are powerful tools to identify key genes that underlie biological processes. One important type of screen uses fluorescence activated cell sorting (FACS) to sort perturbed cells into bins based on the expression level of marker genes, followed by guide RNA (gRNA) sequencing. Analysis of these data presents several statistical challenges due to multiple factors including the discrete nature of the bins and typically small numbers of replicate experiments. To address these challenges, we developed a robust and powerful Bayesian random effects model and software package called Waterbear. Furthermore, we used Waterbear to explore how various experimental design parameters affect statistical power to establish principled guidelines for future screens. Finally, we experimentally validated our experimental design model findings that, when using Waterbear for analysis, high power is maintained even at low cell coverage and a high multiplicity of infection. We anticipate that Waterbear will be of broad utility for analyzing FACS-based CRISPR screens.

Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and a leading cause of neurological disability in young adults. Clinical presentation and disease course are highly heterogeneous. Typically, disease progression occurs over time and is characterized by the gradual accumulation of disability. The risk of developing MS is driven by complex interactions between genetic and environmental factors, including the gut microbiome. How the commensal gut microbiota impacts disease severity and progression over time remains unknown. In a longitudinal study, disability status and associated clinical features in 58 MS patients were tracked over 4.2 ± 0.98 years, and the baseline fecal gut microbiome was characterized via 16S amplicon sequencing. Progressor status, defined as patients with an increase in Expanded Disability Status Scale (EDSS), were correlated with features of the gut microbiome to determine candidate microbiota associated with risk of MS disease progression. We found no overt differences in microbial community diversity and overall structure between MS patients exhibiting disease progression and non-progressors. However, a total of 41 bacterial species were associated with worsening disease, including a marked depletion in Akkermansia, Lachnospiraceae, and Oscillospiraceae, with an expansion of Alloprevotella, Prevotella-9, and Rhodospirillales. Analysis of the metabolic potential of the inferred metagenome from taxa associated with progression revealed enrichment in oxidative stress-inducing aerobic respiration at the expense of microbial vitamin K2 production (linked to Akkermansia), and a depletion in SCFA metabolism (linked to Oscillospiraceae). Further, as a proof of principle, statistical modeling demonstrated that microbiota composition and clinical features were sufficient to predict disease progression. Additionally, we found that constipation, a frequent gastrointestinal comorbidity among MS patients, exhibited a divergent microbial signature compared with progressor status. These results demonstrate a proof of principle for the utility of the gut microbiome for predicting disease progression in MS in a small well-defined cohort. Further, analysis of the inferred metagenome suggested that oxidative stress, vitamin K2, and SCFAs are associated with progression, warranting future functional validation and mechanistic study.

A mild synthetic route to α-nitroso diaryl pyrroles.

A new synthetic method to access α-nitroso pyrroles is presented. This method utilises the nitrosonium salt NOBF4, enabling short reaction times (<10 minutes) and avoiding the harsh acidic conditions usually associated with pyrrole nitrosation. Application of this procedure to diarylated pyrroles yielded several novel nitroso-pyrroles. Modifications to the method, through exclusion of air and inclusion of a mild base, allowed for the nitrosation of pyrroles bearing aryl groups substituted with electron-donating groups. Attempts to nitrosylate pyrroles bearing alkyl substituents resulted in the formation of a dimeric material composed of a pyrrolic unit and a 2-hydroxyimino-protected 1,5-dihydro-2H-pyrrol-2-one.

Language matters for biodiversity.

Language is central to the way people learn about the natural world. A salient concern of the biodiversity conservation arena has been to understand how language can be employed by scientists to communicate knowledge to nonexpert audiences and build ecological literacy. The use of analogy and narrative by scientists are prominent techniques. In this article, we consider how these two modes of language-based reasoning extend into ordinary conversational language use by the public, specifically when articulating everyday understanding and experiences of biodiversity. Drawing on a process of public engagement in a UK woodland environment, a typological framework based on principles of analogical and narrative reasoning is developed to characterize the precise character of processes of everyday biodiversity sense making. The implications of the framework are discussed in the context of future biodiversity research, particularly its participatory and educational dimensions.

Genome-wide associations with longevity and reproductive traits in U.S. rangeland ewes.

Introduction: Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait. Characterizing genetic factors underpinning ewe longevity and related traits could result in the development of genomic selection strategies to improve the stayability of sheep through early, informed selection of replacement ewes. Methods: Towards this aim, a genome-wide association study (GWAS) was performed to identify genetic markers associated with ewe longevity, reproductive, and production traits. Traits evaluated included longevity (i.e., length of time in the flock), parity and the lifetime number of lambs born, lambs born alive, lambs weaned, and weight of lambs weaned. Ewe records from previous studies were used. Specifically, Rambouillet (n = 480), Polypay (n = 404), Suffolk (n = 182), and Columbia (n = 64) breed ewes (N = 1,130) were analyzed against 503,617 SNPs in across-breed and within-breed GWAS conducted with the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model in R. Results: The across-breed GWAS identified 25 significant SNPs and the within-breed GWAS for Rambouillet, Polypay, and Suffolk ewes identified an additional 19 significant SNPs. The most significant markers were rs411309094 (13:22,467,143) associated with longevity in across-breed GWAS (p-value = 8.3E-13) and rs429525276 (2:148,398,336) associated with both longevity (p-value = 6.4E-15) and parity (p-value = 4.8E-15) in Rambouillet GWAS. Significant SNPs were identified within or in proximity (±50 kb) of genes with known or proposed roles in reproduction, dentition, and the immune system. These genes include ALPL, ANOS1, ARHGEF26, ASIC2, ASTN2, ATP8A2, CAMK2D, CEP89, DISC1, ITGB6, KCNH8, MBNL3, MINDY4, MTSS1, PLEKHA7, PRIM2, RNF43, ROBO2, SLCO1A2, TMEM266, TNFRSF21, and ZNF804B. Discussion: This study proposes multiple SNPs as candidates for use in selection indices and suggests genes for further research towards improving understanding of the genetic factors contributing to longevity, reproductive, and production traits of ewes.

Disease progression modelling reveals heterogeneity in trajectories of Lewy-type α-synuclein pathology.

Lewy body (LB) diseases, characterized by the aggregation of misfolded α-synuclein proteins, exhibit notable clinical heterogeneity. This may be due to variations in accumulation patterns of LB neuropathology. Here we apply a data-driven disease progression model to regional neuropathological LB density scores from 814 brain donors with Lewy pathology. We describe three inferred trajectories of LB pathology that are characterized by differing clinicopathological presentation and longitudinal antemortem clinical progression. Most donors (81.9%) show earliest pathology in the olfactory bulb, followed by accumulation in either limbic (60.8%) or brainstem (21.1%) regions. The remaining donors (18.1%) initially exhibit abnormalities in brainstem regions. Early limbic pathology is associated with Alzheimer's disease-associated characteristics while early brainstem pathology is associated with progressive motor impairment and substantial LB pathology outside of the brain. Our data provides evidence for heterogeneity in the temporal spread of LB pathology, possibly explaining some of the clinical disparities observed in Lewy body disease.

Primary Practice Patterns For The Initial Management of Open Angle Glaucoma.

PRCIS: About 1/4th of survey respondents from an ASCRS database initiate treatment for primary open-angle glaucoma (POAG) with laser trabeculoplasty. Factors impacting physicians' choice of laser versus topical treatment for POAG were explored. PURPOSE: To characterize primary treatment preferences (topical medication vs. laser trabeculoplasty or intracameral sustained release implants) in primary open-angle glaucoma (POAG) patients and determine factors related to primary intervention selection. METHODS: A 33-question survey was distributed to an American Society of Cataract and Refractive Surgery database on treatment choices made by ophthalmologists for POAG. Data collected included country of practice, years of practice, completion of glaucoma fellowship training, type of practice, and preference for first line of treatment of POAG. Multiple logit regression was used to compare the effect of covariates on physicians' choice of either topical medication or laser trabeculoplasty for POAG. RESULTS: A total of 252/19,246 (1.3%) of surveys were returned. Almost three-quarters of respondents utilized topical medication as first line of treatment for POAG (73.6%) while 26.4% preferred to start with laser treatment. Significant variables associated with the selection of laser (vs. drops) are practicing in the U.S. (odds ratio [OR] 2.85, 95% confidence interval [CI] 1.33-6.10), more recent completion of ophthalmology residency (OR 1.95, 95% CI 1.00-3.77), greater volume of minimally invasive glaucoma surgeries (MIGS) (OR 1.68, 95% CI 1.18-2.40), and a glaucoma patient base greater than 25% (OR 2.21, 95% CI 1.09-4.48). CONCLUSIONS: For the first line treatment of POAG, laser trabeculoplasty is more likely to be preferred, over topical drops, by U.S. physicians who are relatively new in practice, who have a larger glaucoma patient base and who perform more MIGS.

Thermal performance curves for aerobic scope and specific dynamic action in a sexually dimorphic piscivore: implications for a warming climate.

Digestion can make up a substantial proportion of animal energy budgets, yet our understanding of how it varies with sex, body mass and ration size is limited. A warming climate may have consequences for animal growth and feeding dynamics that will differentially impact individuals in their ability to efficiently acquire and assimilate meals. Many species, such as walleye (Sander vitreus), exhibit sexual size dimorphism (SSD), whereby one sex is larger than the other, suggesting sex differences in energy acquisition and/or expenditure. Here, we present the first thorough estimates of specific dynamic action (SDA) in adult walleye using intermittent-flow respirometry. We fed male (n=14) and female (n=9) walleye two ration sizes, 2% and 4% of individual body mass, over a range of temperatures from 2 to 20°C. SDA was shorter in duration and reached higher peak rates of oxygen consumption with increasing temperature. Peak SDA increased with ration size and decreased with body mass. The proportion of digestible energy lost to SDA (i.e. the SDA coefficient) was consistent at 6% and was unrelated to temperature, body mass, sex or ration size. Our findings suggest that sex has a negligible role in shaping SDA, nor is SDA a contributor to SSD for this species. Standard and maximum metabolic rates were similar between sexes but maximum metabolic rate decreased drastically with body mass. Large fish, which are important for population growth because of reproductive hyperallometry, may therefore face a bioenergetic disadvantage and struggle most to perform optimally in future, warmer waters.

Deciphering the functional specialization of whole-brain spatiomolecular gradients in the adult brain.

Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning. The interaction of these spatiomolecular gradients i) accurately reconstructs the position of brain tissue samples, ii) delineates known functional territories, and iii) can model the topographical variation of diverse cortical features. The spatiomolecular gradients are distinct from canonical cortical axes differentiating the primary sensory cortex from the association cortex, but radiate in parallel with the axes traversed by local field potentials along the cortex. We replicate all three molecular gradients in three independent human datasets as well as two nonhuman primate datasets and find that each gradient shows a distinct developmental trajectory across the lifespan. The gradients are composed of several well-known transcription factors (e.g., PAX6 and SIX3), and a small set of genes shared across gradients are strongly enriched for multiple diseases. Together, these results provide insight into the developmental sculpting of functionally distinct brain regions, governed by three robust transcriptomic axes embedded within brain parenchyma.

Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells.

Cis-regulatory elements (CREs) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes CD28, CTLA4 and ICOS, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.

Accelerometer-based swimming metabolism of smallmouth bass (Micropterus dolomieu).

Bioenergetics is informative for a range of fundamental and applied resource management questions, but findings are often constrained by a lack of ecological realism due to the challenges of remotely estimating key parameters such as metabolic rate. To enable field applications, we conducted a calibration study with smallmouth bass (Micropterus dolomieu, 0.7-2 kg) surgically implanted with accelerometer transmitters and exposed to a ramp-Ucrit swimming protocol in a swim tunnel respirometer across a range of water temperatures (6, 12, 18, and 24°C). There was an exponential increase in fish acceleration with swimming speed, and acceleration per speed was higher in smaller fish and female fish, and at colder temperatures. Mass-specific fish metabolic rate (MO2; mg O2 kg-1 h-1) increased with swimming speed, acceleration, and temperature, and decreased with fish mass, which when combined were strong predictors of MO2. Maximum metabolic rate (MMR) was estimated to peak at 22°C, but maximum sustained swimming speed (Ucrit) remained high at c. 90-100 m s-1 above 20°C, based on second-order polynomial functions. Aerobic scope (AS) estimates peaked at 20°C (>90% AS at 17-24°C; >50% AS at 11-28°C). Males exhibited marginally higher MMR, AS, and Ucrit than females at higher temperatures. Larger fish generally exhibited higher Ucrit, but smaller fish had a marginally broader performance range (AS, Ucrit) among temperatures, benefiting from higher MMR despite a steeper increase in resting metabolic rate with temperature. These findings enable field studies to estimate metabolic metrics of smallmouth bass in situ to characterize their ecological energetics and inform bioenergetics models.

Comparing HEDIS performance of Dual Eligible Special Needs Plans with other coverage types for dually eligible people.

People eligible for both Medicare and Medicaid coverage ("dually eligible individuals") have lower levels of income and assets and often higher health care needs and costs than those eligible for Medicare but not Medicaid coverage. Their 3 most common Medicare coverage options are Medicare Advantage (MA) Dual Eligible Special Needs Plans (D-SNPs), non-D-SNP MA plans, and fee-for-service (FFS) Medicare with a stand-alone prescription drug plan. No prior study has examined clinical quality of care for dually eligible individuals across these 3 coverage types. To fill that void, we used logistic regression to compare these coverage types on 6 HEDIS measures of clinical quality of care that were available for both MA and FFS (constructed from claims files). D-SNPs and non-D-SNP MA plans significantly outperformed FFS for all 6 measures for dually eligible individuals, by approximately 5 percentage points for 2 measures and by 18-34 percentage points for the other 4 measures. For the 4 measures with the greatest advantage over FFS, performance was 3-8 percentage points higher in D-SNPs than in non-D-SNP MA plans.

Effect of EVAR on International Ruptured AAA Mortality-Sex and Geographic Disparities.

Background: We sought to investigate the differential impact of EVAR (endovascular aneurysm repair) vis-à-vis OSR (open surgical repair) on ruptured AAA (abdominal aortic aneurysm) mortality by sex and geographically. Methods: We performed a retrospective study of administrative data on EVAR from state statistical agencies, vascular registries, and academic publications, as well as ruptured AAA mortality rates from the World Health Organization for 14 14 states across Australasia, East Asia, Europe, and North America. Results: Between 2011-2016, the proportion of treatment of ruptured AAAs by EVAR increased from 26.1 to 43.8 percent among females, and from 25.7 to 41.2 percent among males, and age-adjusted ruptured AAA mortality rates fell from 12.62 to 9.50 per million among females, and from 34.14 to 26.54 per million among males. The association of EVAR with reduced mortality was more than three times larger (2.2 vis-à-vis 0.6 percent of prevalence per 10 percentage point increase in EVAR) among females than males. The association of EVAR with reduced mortality was substantially larger (1.7 vis-à-vis 1.1 percent of prevalence per 10 percentage point increase in EVAR) among East Asian states than European+ states. Conclusions: The increasing adoption of EVAR coincided with a decrease in ruptured AAA mortality. The relationship between EVAR and mortality was more pronounced among females than males, and in East Asian than European+ states. Sex and ethnic heterogeneity should be further investigated.

A series of potent BODIPY photosensitisers featuring tellurophene motifs at boron.

This article describes the synthesis and photophysical properties of a series of BODIPY photosensitisers that feature tellurophene motifs appended at the boron centre. These compounds were obtained via nucleophilic substitution of various F-BODIPYs with lithiated tellurophene. The synthetic scope, photophysical characteristics and photosensitisation properties are discussed. Structural modifications around the BODIPY core resulted in an eight-fold improvement in light IC50 values compared to previous designs.