Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.

Transmembrane protease, serine 2 (TMPRSS2) has been identified as key host cell factor for viral entry and pathogenesis of SARS-CoV-2. Specifically, TMPRSS2 proteolytically processes the SARS-CoV-2 Spike (S) protein, enabling virus-host membrane fusion and infection of the airways. We present here a recombinant production strategy for enzymatically active TMPRSS2 and characterization of its matured proteolytic activity, as well as its 1.95 Å X-ray cocrystal structure with the synthetic protease inhibitor nafamostat. Our study provides a structural basis for the potent but nonspecific inhibition by nafamostat and identifies distinguishing features of the TMPRSS2 substrate binding pocket that explain specificity. TMPRSS2 cleaved SARS-CoV-2 S protein at multiple sites, including the canonical S1/S2 cleavage site. We ranked the potency of clinical protease inhibitors with half-maximal inhibitory concentrations ranging from 1.4 nM to 120 µM and determined inhibitor mechanisms of action, providing the groundwork for drug development efforts to selectively inhibit TMPRSS2.

Association between right ventricular global longitudinal strain and mortality in intermediate-risk pulmonary embolism.

BACKGROUND: Right ventricular (RV) systolic dysfunction has been identified as a prognostic marker for adverse clinical events in patients presenting with acute pulmonary embolism (PE). However, challenges exist in identifying RV dysfunction using conventional echocardiography techniques. Strain echocardiography is an evolving imaging modality which measures myocardial deformation and can be used as an objective index of RV systolic function. This study evaluated RV Global Longitudinal Strain (RVGLS) in patients with intermediate risk PE as a parameter of RV dysfunction, and compared to traditional echocardiographic and CT parameters evaluating short-term mortality. METHODS: Retrospective single center cohort study of 251 patients with intermediate-risk PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Statistical analysis evaluated each parameter comparing survivors versus non-survivors at 30 days. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for comparison of the two cohorts. RESULTS: Altogether 251 patients were evaluated. Overall mortality rate was 12.4%. Utilizing an ROC curve, an absolute cutoff value of 17.7 for RVGLS demonstrated a sensitivity of 93% and specificity of 70% for observed 30-day mortality. Individuals with an RVGLS ≤17.7 had a 25 times higher mortality rate than those with RVGLS above 17.7 (HR 25.24, 95% CI = 6.0-106.4, p < .001). Area under the curve was (.855), RVGLS outperformed traditional echocardiographic parameters, CT findings, and cardiac biomarkers on univariable and multivariable analysis. CONCLUSIONS: Reduced RVGLS values on initial echocardiographic assessment of patients with intermediate-risk PE identified patients at higher risk for mortality at 30 days.

Robotic colorectal surgery in the emergent diverticulitis setting: is it safe? A review of large national database.

BACKGROUND: As robotic colorectal surgery continues to advance in conjunction with improved recovery protocols, we began implementing robotic surgery (RS) as an option for emergent diverticulitis surgery. Our hospital system utilizes the Da Vinci Xi system, and staff are required to undergo training, making emergent colorectal surgery a feasible option. However, it is essential to determine the safety with reproducibility of our experiences. METHODS: A de-identified retrospective review was performed of Intuitive's national database which obtained data from 262 facilities from January 2018 through December 2021. This identified over 22,000 emergent colorectal surgeries. Of those, over 2500 were performed for diverticulitis in which 126 were RS, 446 laparoscopic surgery (LS), and 1952 open surgery (OS). Clinical outcome metrics including conversion rates, anastomotic leaks, intensive care unit (ICU) admissions, length of stay, mortality, and readmissions were obtained. The cohort was defined by patients who were seen in the emergency department (ED) with diverticulitis and proceeded to have a sigmoid colectomy within 24 h of ED arrival. RESULTS: RS was associated with increased operating time (RS 262, LS 207, OS 182 min), but data has shown many benefits of emergent RS compared to OS. We identified significant decreases in ICU admission rates (OS 19.0%, RS 9.5%, p = 0.01) and anastomotic leak rates (OS 4.4%, RS 0.8%, p = 0.04), with borderline improvement in overall length of stay (OS 9.9, RS 8.9 days, p = 0.05). When compared with LS, RS showed many comparable results. However, RS witnessed a statistically significant improvement in anastomotic leak rates (LS 4.5%, RS 0.8%, p = 0.04). Importantly, there was a striking difference in conversion rates to OS. LS converted over 28.7% of cases to OS, whereas RS only converted 7.9%, p = 0.000005. CONCLUSION: Given these findings, RS is another MIS tool that could be a safe and feasible option for the acute management of emergent diverticulitis.

Pyrophosphate release acts as a kinetic checkpoint during high-fidelity DNA replication by the Staphylococcus aureus replicative polymerase PolC.

Bacterial replication is a fast and accurate process, with the bulk of genome duplication being catalyzed by the α subunit of DNA polymerase III within the bacterial replisome. Structural and biochemical studies have elucidated the overall properties of these polymerases, including how they interact with other components of the replisome, but have only begun to define the enzymatic mechanism of nucleotide incorporation. Using transient-state methods, we have determined the kinetic mechanism of accurate replication by PolC, the replicative polymerase from the Gram-positive pathogen Staphylococcus aureus. Remarkably, PolC can recognize the presence of the next correct nucleotide prior to completing the addition of the current nucleotide. By modulating the rate of pyrophosphate byproduct release, PolC can tune the speed of DNA synthesis in response to the concentration of the next incoming nucleotide. The kinetic mechanism described here would allow PolC to perform high fidelity replication in response to diverse cellular environments.

Cardiovascular assessment in cirrhosis: is global longitudinal strain altered in cirrhosis? A meta-analysis and review.

BACKGROUND AND AIMS: Evaluation of cardiac function and determining the potential risk of cardiac complications with liver transplantation has been both a topic of contention and discussion. Global longitudinal strain (GLS) imaging has been used to identify subclinical myocardial dysfunction in other pathologies; however, its use in the cirrhosis population is unclear. A meta-analysis was performed to assess GLS values in patients with cirrhosis compared to healthy controls. METHODS: A literature search was conducted for studies that evaluated GLS in patients with cirrhosis compared to healthy controls published until September 18, 2020. Primary outcomes looked at differences in GLS values between these populations. RESULTS: Thirteen total studies were included in the meta-analysis. Overall, 802 patients with cirrhosis and 540 healthy controls were included in the analysis. The GLS values were numerically more negative in the healthy control group versus patients with cirrhosis (raw mean difference -2.5%, 95% CI -3 to -1.9, P = < .001), I2  = 81%. CONCLUSION: GLS can be used as an early marker of subclinical myocardial dysfunction. We noted a difference in GLS values in patients with cirrhosis compared to healthy control subjects in this meta-analysis. Other traditional systolic and diastolic echocardiographic parameters were not found to be significantly different between patients with cirrhosis versus healthy controls. This may indicate utilization of GLS when screening for cardiac dysfunction prior to liver transplantation.

The Experiences of Endurance Athletes With Atrial Fibrillation: Tensions and Takeaways.

BACKGROUND: Growing evidence indicates that chronic high-intensity endurance exercise predisposes male, middle-aged athletes to increased risk of atrial fibrillation (AF). The aetiology of AF in endurance athletes is multifactorial and remains incompletely understood. Despite their unique training demands, AF care in athletes remains largely based on evidence derived from the general population. Understanding the experiences of athletes with AF provides a necessary foundation for addressing challenges in managing their condition and identifying gaps in care. AIM: The purpose of this interpretive descriptive qualitative study was to describe the experiences and perspectives of endurance athletes living with AF. METHOD: Masters athletes diagnosed with AF and aged between 35 and 60 years were recruited internationally through cardiology practices and social media. Ten middle-aged, male endurance athletes with AF and >1,500 lifetime training hours participated in individual, semi-structured interviews. Data were analysed using inductive thematic analysis. RESULTS: Three key themes were constructed: (1) tensions with training, (2) tensions with treatment plans, and (3) tensions with clinicians. Participants experienced a wide range of symptoms from AF that significantly affected their ability to train, and reacted negatively to medical treatment strategies that affected their exercise capacity and training performance. Athletes experienced tensions with providers who failed to acknowledge their athletic needs. CONCLUSIONS: Our results highlight the unique difficulties that male athletes with AF face in navigating between training and their disease, treatment, and clinicians. Shared decision-making between the athlete and provider is likely necessary for effective management of athletic AF.

Synthesis and Preclinical Evaluation of Three Novel 68Ga-Labeled Bispecific PSMA/FAP-Targeting Tracers for Prostate Cancer Imaging.

Tumor heterogeneity limits the efficacy and reliability of monospecific radiopharmaceuticals in prostate cancer diagnosis and therapy. To overcome this limitation and improve lesion detection sensitivity, we developed and evaluated three bispecific radiotracers that can target both prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are the two key proteins overexpressed in prostate cancer. Three FAP-targeting ligands with various linker lengths were synthesized through multistep organic synthesis, and then connected to the PSMA-targeting motif. IC50(PSMA) and IC50(FAP) values of Ga-complexed bispecific ligands, Ga-AV01017, Ga-AV01030, and Ga-AV01038 were 25.2-71.6 and 1.25-2.74 nM, respectively. The uptake values in PSMA-expressing LNCaP tumor xenografts were 4.38 ± 0.55, 5.17 ± 0.51, and 4.25 ± 0.86 %ID/g for [68Ga]Ga-AV01017, [68Ga]Ga-AV01030, and [68Ga]Ga-AV01038, respectively, which were lower than the monospecific PSMA-targeting tracer [68Ga]Ga-HTK03041 (23.1 ± 6.11 %ID/g). The uptake values in FAP-expressing HEK293T:hFAP tumor xenografts were 2.99 ± 0.37, 3.69 ± 0.81, 3.64 ± 0.83 %ID/g for [68Ga]Ga-AV01017, [68Ga]Ga-AV01030, and [68Ga]Ga-AV01038, respectively, which were also lower than the monospecific FAP-targeting tracer, [68Ga]Ga-FAPI-04 (12.5 ± 2.00 %ID/g). We observed that the bispecific tracers had prolonged blood retention, in which tracers with a longer linker tend to have a higher blood uptake and lower tumor uptake. Further investigations are needed to optimize the linker selection to generate promising bispecific PSMA/FAP-targeting tracers for prostate cancer imaging.

Characterizing dark state kinetics and single molecule fluorescence of FusionRed and FusionRed-MQ at low irradiances.

The presence of dark states causes fluorescence intermittency of single molecules due to transitions between "on" and "off" states. Genetically encodable markers such as fluorescent proteins (FPs) exhibit dark states that make several super-resolved single-molecule localization microscopy (SMLM) methods possible. However, studies quantifying the timescales and nature of dark state behavior for commonly used FPs under conditions typical of widefield and total internal reflection fluorescence (TIRF) microscopy remain scarce and pre-date many new SMLM techniques. FusionRed is a relatively bright red FP exhibiting fluorescence intermittency and has thus been identified as a potential candidate for SMLM. We herein characterize the rates for dark-state conversion and the subsequent ground-state recovery of FusionRed and its 2.5-fold brighter descendent FusionRed L175M M42Q (FusionRed-MQ) at low irradiances (1-10 W cm-2), which were previously unexplored experimental conditions. We characterized the kinetics of dark state transitions in these two FPs by using single molecule blinking and ensemble photobleaching experiments bridged with a dark state kinetic model. We find that at low irradiances, the recovery process to the ground state is minimally light-driven and FusionRed-MQ has a 1.3-fold longer ground state recovery time indicating a conformationally restricted dark-state chromophore in comparison to FusionRed. Our studies indicate that the brighter FusionRed-MQ variant exhibits higher dark state conversion rates with longer ground state recovery lifetimes, thus it is potentially a better candidate for SMLM applications than its progenitor FusionRed.

Seal body condition and atmospheric circulation patterns influence polar bear body condition, recruitment, and feeding ecology in the Chukchi Sea.

Polar bears (Ursus maritimus) are experiencing loss of sea ice habitats used to access their marine mammal prey. Simultaneously, ocean warming is changing ecosystems that support marine mammal populations. The interactive effects of sea ice and prey are not well understood yet may explain spatial-temporal variation in the response of polar bears to sea ice loss. Here, we examined the potential combined effects of sea ice, seal body condition, and atmospheric circulation patterns on the body condition, recruitment, diet, and feeding probability of 469 polar bears captured in the Chukchi Sea, 2008-2017. The body condition of ringed seals (Pusa hispida), the primary prey of females and subadults, was related to dietary proportions of ringed seal, feeding probability, and the body condition of females and cubs. In contrast, adult males consumed more bearded seals (Erignathus barbatus) and exhibited better condition when bearded seal body condition was higher. The litter size, number of yearlings per adult female, and the condition of dependent young were higher following winters characterized by low Arctic Oscillation conditions, consistent with a growing number of studies. Body condition, recruitment, and feeding probability were either not associated or negatively associated with sea ice conditions, suggesting that, unlike some subpopulations, Chukchi Sea bears are not currently limited by sea ice availability. However, spring sea ice cover declined 2% per year during our study reaching levels not previously observed in the satellite record and resulting in the loss of polar bear hunting and seal pupping habitat. Our study suggests that the status of ice seal populations is likely an important factor that can either compound or mitigate the response of polar bears to sea ice loss over the short term. In the long term, neither polar bears nor their prey are likely robust to limitless loss of their sea ice habitat.

Mapping potential effects of proposed roads on migratory connectivity for a highly mobile herbivore using circuit theory.

Migration is common worldwide as species access spatiotemporally varying resources and avoid predators and parasites. However, long-distance migrations are increasingly imperiled due to development and habitat fragmentation. Improved understanding of migratory behavior has implications for conservation and management of migratory species, allowing identification and protection of seasonal ranges and migration corridors. We present a technique that applies circuit theory to predict future effects of development by analyzing season-specific resistance to movement from anthropogenic and natural environmental features across an entire migratory path. We demonstrate the utility of our approach by examining potential effects of a proposed road system on barren ground caribou (Rangifer tarandus granti) and subsistence hunters in northern Alaska. Resource selection functions revealed migratory selection by caribou. We tested five scenarios relating habitat selection to landscape resistance using Circuitscape and GPS telemetry data. To examine the effect of potential roads on connectivity of migrating animals and human hunters, we compared current flow values near communities in the presence of proposed roads. Caribou avoided dense vegetation, rugged terrain, major rivers, and existing roads in both spring and fall. A negative linear relationship between resource selection and landscape resistance was strongly supported for fall migration while spring migration featured a negative logarithmic relationship. Overall patterns of caribou connectivity remained similar in the presence of proposed roads, though reduced current flow was predicted for communities near the center of current migration areas. Such data can inform decisions to allow or disallow projects or to select among alternative development proposals and mitigation measures, though consideration of cumulative effects of development is needed. Our approach is flexible and can easily be adapted to other species, locations and development scenarios to expand understanding of movement behavior and to evaluate proposed developments. Such information is vital to inform policy decisions that balance new development, resource user needs, and preservation of ecosystem function.

Demographic risk assessment for a harvested species threatened by climate change: polar bears in the Chukchi Sea.

Climate change threatens global biodiversity. Many species vulnerable to climate change are important to humans for nutritional, cultural, and economic reasons. Polar bears Ursus maritimus are threatened by sea-ice loss and represent a subsistence resource for Indigenous people. We applied a novel population modeling-management framework that is based on species life history and accounts for habitat loss to evaluate subsistence harvest for the Chukchi Sea (CS) polar bear subpopulation. Harvest strategies followed a state-dependent approach under which new data were used to update the harvest on a predetermined management interval. We found that a harvest strategy with a starting total harvest rate of 2.7% (˜85 bears/yr at current abundance), a 2:1 male-to-female ratio, and a 10-yr management interval would likely maintain subpopulation abundance above maximum net productivity level for the next 35 yr (approximately three polar bear generations), our primary criterion for sustainability. Plausible bounds on starting total harvest rate were 1.7-3.9%, where the range reflects uncertainty due to sampling variation, environmental variation, model selection, and differing levels of risk tolerance. The risk of undesired demographic outcomes (e.g., overharvest) was positively related to harvest rate, management interval, and projected declines in environmental carrying capacity; and negatively related to precision in population data. Results reflect several lines of evidence that the CS subpopulation has been productive in recent years, although it is uncertain how long this will last as sea-ice loss continues. Our methods provide a template for balancing trade-offs among protection, use, research investment, and other factors. Demographic risk assessment and state-dependent management will become increasingly important for harvested species, like polar bears, that exhibit spatiotemporal variation in their response to climate change.

The CADILLAC risk score accurately identifies patients at low risk for in-hospital mortality and adverse cardiovascular events following ST elevation myocardial infarction.

BACKGROUND: The CADILLAC risk score was developed to identify patients at low risk for adverse cardiovascular events following ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS: We performed a single center retrospective review of STEMI hospitalizations treated with PPCI from 2014 to 2018. Patients were stratified using the CADILLAC risk score into low risk, intermediate risk and high risk groups. Patients presenting with cardiac arrest or cardiogenic shock were excluded from the study. The primary outcome was adverse clinical events during initial hospitalization. Secondary outcomes were adverse clinical events at 30 days and 1 year following index hospitalization. RESULTS: The study included 341 patients. Compared to patients with a low CADILLAC score, adverse clinical events were similar in the intermediate risk group during hospitalization (OR 1.23, CI 0.37-4.05, p 0.733) and at 30 days (OR 2.27, CI 0.93-5.56, p 0.0733) while adverse clinical events were significantly elevated in the high risk group during hospitalization (OR 4.75, CI 1.91-11.84, p 0.0008) and at 30 days (OR 8.73, CI 4.02-18.96, p < 0.0001). At 1 year follow-up, compared to the low risk CADILLAC group (9.4% adverse clinical event rate), cumulative adverse clinical events were significantly higher in the intermediate risk group (22.9% event rate, OR 2.86, CI 1.39-5.89, p 0.0044) and in the elevated risk group (58.6% event rate, OR 13.67, CI 6.81-27.43, p < 0.0001). The mortality rate was 0% for patients defined at low risk by CADILLAC score during hospitalization, as well up to 1 year follow up. On receiver operating curve analysis, discrimination of in-hospital adverse clinical events was fair using CADILLAC (C = 0.66, odds ratio 1.18; 95% CI 1.04-1.33; p = 0.0064) with somewhat better discrimination at 30-day follow-up (C = 0.719) and 1-year follow-up (C = 0.715). CONCLUSION: Patients defined as low risk by the CADILLAC score following a STEMI were associated with lower mortality and adverse clinical event rates during hospitalization and up to 1 year following STEMI when compared to those with an intermediate or high CADILLAC score.

Observation and Analysis of Large Dynamic Frequency Shifts in the 1H NMR Signals of H-D in Deuterium-Substituted Dihydrogen Complexes.

A dynamic frequency shift (DFS) in the 1H NMR resonance of the HD unit of the deuterium-labeled dihydrogen complex [Ru(D)(η2-HD)(P3P3iPr)][BPh4] [P3P3iPr = P(CH2CH2CH2PiPr2)3] has been observed and analyzed. To the best of our knowledge, this is the first demonstration of the DFS for a H-D pair. The observed DFS of the center line relative to the outside lines in the H-D triplet is large, up to ∼11 Hz, because of the short H-D distance encountered in dihydrogen complexes. Analysis of the DFS as a function of the temperature, combined with density-functional-theory-calculated or least-squares-fitted electric-field-gradient (EFG) parameters, suggests an H-D bond length of 0.92-0.94 Å. A DFS was also observed in trans-[Fe(η2-HD)(H)(dppe)2]+, suggesting the DFS will be commonplace in dihydrogen complexes if appropriate conditions are employed for its observation. Possible applications of the DFS as a probe of the bond lengths, EFGs, and molecular motion, particularly in inorganic systems, are discussed.

The Symptom Experience of Patients With Atrial Fibrillation Before Their Initial Diagnosis.

BACKGROUND: Atrial fibrillation (AF), the most common form of dysrhythmia, steadily increases in prevalence with age. If left untreated, AF significantly increases the risk of stroke, heart failure, and death. Despite the increasing prevalence, there are significant research gaps in the prediagnosis symptom experiences of patients with AF. OBJECTIVE: The purpose of this qualitative descriptive study was to explore the prediagnosis symptom experience of patients with AF. METHODS: Participants 19 years or older with AF diagnosed in the previous year were recruited (n = 26) from outpatient cardiac rehabilitation and AF clinics. Semistructured interviews, broadly guided by the Symptom Experience Model, explored perceptions, evaluations, and responses to AF symptoms. Thematic analysis used a 2-step approach, deductively coding for participants' symptom perceptions, evaluations, and responses and inductively coding within these broader Symptom Experience Model concepts. RESULTS: Perception involved awareness of bodily sensations, ranging from imperceptible noticing to commanding attention, heightened by rest and activity. In evaluation, participants used self-derived theories to explain their symptoms, gathered evidence to support/refute their theories, and formulated alternative theories as symptoms changed over time. Responses consisted of nontreatment, self-treatment, and health seeking; most participants needed repeated healthcare visits before diagnosis. CONCLUSIONS: The current study identified challenges participants experienced in developing awareness of their AF symptoms, the complex cognitive processes associated with evaluation, and barriers that made it difficult to respond to AF symptoms in a timely manner. Understanding the prediagnosis symptom experience from the patient's perspective is essential for the enhancement of current AF screening practices.

Transitions in Atrial Fibrillation Care: A Systematic Review.

BACKGROUND: Patients with atrial fibrillation (AF) commonly transition between care settings and providers. These transitions are often points in the health care system where errors and clinical deterioration can occur. Anticoagulation interruption or discontinuation and sub-optimal follow-up post-emergency department (ED) discharge are considered major transitional issues. OBJECTIVE: The purpose of this study was to synthesise the evidence examining the impact of transitional care interventions on patient, provider, and health care utilisation outcomes. METHODS: This systematic mixed studies review examined citations from four databases Medline, CINAHL, EMBASE, and Cochrane Central Controlled Register of Trials (CENTRAL) using relevant search terms. Fourteen (14) moderate to high quality articles were selected. RESULTS: The available evidence reporting impacts of transitional interventions on health care utilisation, provider, and patient outcomes in AF patients is mixed and of variable quality. The stronger evidence revealed improvements in patient outcomes including knowledge, quality of life, and medication adherence and increased provider anticoagulant prescriptions resulting from transitional interventions. Hospital admissions and ED visits were not significantly affected by any interventions. CONCLUSIONS: Apps and educational toolkits improved patient knowledge. Pathways increased patient quality of life and provider prescription rates. There is a need for more research to determine the AF transition interventions which maximise patient, provider and health care outcomes.

Popcorn Capsulorrhaphy in Revision Aesthetic Breast Surgery.

BACKGROUND: Control of the pocket in revisional breast surgery can be technically challenging and unpredictable. A capsulorrhaphy technique has been utilized in altering capsules in secondary aesthetic breast surgery. OBJECTIVES: The authors sought to determine the effectiveness of popcorn capsulorrhaphy in revisional breast surgery. METHODS: A retrospective chart review of revisional breast cases utilizing popcorn capsulorrhaphy was conducted between September 2015 and August 2017. Only aesthetic breast cases were included. Data were collected for 149 patients. RESULTS: One hundred forty-nine patients representing 266 breasts were operated on. The average patient age was 42 years and the mean body mass index was 24.2 kg/m2. The average time from their original surgery to the popcorn capsulorrhaphy secondary procedure was 9.3 years. Indications for capsulorrhaphy included malposition in 163 breasts (61.3%), implant positioning for breast ptosis in 34 breasts (12.8%), pocket adjustment for implant size change in 49 breasts (18.4%), and postexplantation pocket reduction in 20 breasts (7.5%). Of the 266 implants, 145 (54.5%) were smooth, 101 (38%) textured, and 20 (7.5%) were explanted. The average original implant size was 405 cc and the average size placed at the time of capsulorrhaphy was 422 cc. Two hundred thirty-six (88.7%) were in a submuscular pocket and 30 (11.3%) were subglandular. The total number of complications was 39 (14.7%), and 16 (6%) required some type of operative revision. CONCLUSIONS: Popcorn capsulorrhaphy can provide pocket control and stability with low complication and revision rates. The addition of a mesh or biologic at the time of popcorn capsulorrhaphy can further lower the complication and revision rates.

Characteristics of and current practice patterns of pacing for high-degree atrioventricular block after transcatheter aortic valve implantation in comparison to surgical aortic valve replacement.

OBJECTIVE: We aimed to investigate the current practice patterns of permanent pacing, especially the timing of implantation, for high-degree AV block (HDAVB) following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). BACKGROUND: Comparative data regarding current practice patterns of permanent pacing for HDAVB between TAVI and SAVR is limited. METHODS: Using the National Inpatient Sample database, we identified patients who underwent TAVI or SAVR between 2012 and 2014. The incidence of HDAVB, the rate of permanent pacemaker implantation, and the timing of implantations were compared between TAVI and SAVR groups. RESULTS: We identified 33 690 and 202 110 patients who underwent TAVI and SAVR, respectively. HDAVB occurred in 3480 patients (10.3%) in the TAVI group and 11 405 patients (5.6%) in the SAVR group (P < 0.001). Among the patients who developed HDAVB, patients in the TAVI group were more likely to undergo permanent pacemaker implantation than those in the SAVR group (74.1% vs 64.7%; P < 0.001). The median interval from TAVI to pacemaker implantation was 2 days (interquartile range 1-3 days) vs 5 days (interquartile range 3-7 days) from SAVR to pacemaker implantation (P < 0.001). Among the patients who developed HDAVB, TAVI was associated with higher rates of permanent pacemaker implantation after adjusting for other comorbidities (odds ratio 1.41:95% confidence interval 1.13-1.77; P = 0.003). CONCLUSIONS: HDAVB occurred more commonly after TAVI compared to SAVR. HDAVB after TAVI compared to SAVR was associated with a higher rate of permanent pacemaker implantation at an earlier timing from the index procedure.

Accounting for phenology in the analysis of animal movement.

The analysis of animal tracking data provides important scientific understanding and discovery in ecology. Observations of animal trajectories using telemetry devices provide researchers with information about the way animals interact with their environment and each other. For many species, specific geographical features in the landscape can have a strong effect on behavior. Such features may correspond to a single point (eg, dens or kill sites), or to higher dimensional subspaces (eg, rivers or lakes). Features may be relatively static in time (eg, coastlines or home-range centers), or may be dynamic (eg, sea ice extent or areas of high-quality forage for herbivores). We introduce a novel model for animal movement that incorporates active selection for dynamic features in a landscape. Our approach is motivated by the study of polar bear (Ursus maritimus) movement. During the sea ice melt season, polar bears spend much of their time on sea ice above shallow, biologically productive water where they hunt seals. The changing distribution and characteristics of sea ice throughout the year mean that the location of valuable habitat is constantly shifting. We develop a model for the movement of polar bears that accounts for the effect of this important landscape feature. We introduce a two-stage procedure for approximate Bayesian inference that allows us to analyze over 300 000 observed locations of 186 polar bears from 2012 to 2016. We use our model to estimate a spatial boundary of interest to wildlife managers that separates two subpopulations of polar bears from the Beaufort and Chukchi seas.

Assessing cardiovascular risk in the prerenal transplant population: Comparison of myocardial perfusion imaging and coronary angiography with risk factor stratification.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have a higher incidence of coronary artery disease (CAD). Hence, it is crucial to evaluate CAD before renal transplantation. This study compares the utility of pharmacologic single-photon emission computed-tomography (SPECT) imaging directly to coronary angiography for diagnosis of CAD with correlation to cardiovascular risk factors. METHOD: Retrospective review of asymptomatic renal failure patients who underwent both SPECT and coronary angiography to identify obstructive CAD between the years 2008-2016. Ninety-four ESRD subjects were evaluated. RESULTS: Myocardial perfusion SPECT study found, when compared to coronary angiography demonstrated for CAD, the sensitivity of 93.3% with a specificity of 73.4%. Importantly, the negative predictive value for coronary artery disease was 96%. With seven or more cardiac risk factors, 66.7% of patients had obstructive coronary artery disease. Among all the risk factors examined, patients with a previous history of coronary artery disease had a 68% risk of obstructive coronary artery disease. CONCLUSION: Comparing myocardial perfusion imaging SPECT findings with coronary angiography in patients with ESRD, a sensitivity of 93.3% and a specificity of 73% were observed. Of all the risk factors examined, patient with the previous history of CAD was the single most significant risk factor for CAD in 68% of cases.

Blazing Signature Filter: a library for fast pairwise similarity comparisons.

BACKGROUND: Identifying similarities between datasets is a fundamental task in data mining and has become an integral part of modern scientific investigation. Whether the task is to identify co-expressed genes in large-scale expression surveys or to predict combinations of gene knockouts which would elicit a similar phenotype, the underlying computational task is often a multi-dimensional similarity test. As datasets continue to grow, improvements to the efficiency, sensitivity or specificity of such computation will have broad impacts as it allows scientists to more completely explore the wealth of scientific data. RESULTS: The Blazing Signature Filter (BSF) is a highly efficient pairwise similarity algorithm which enables extensive data mining within a reasonable amount of time. The algorithm transforms datasets into binary metrics, allowing it to utilize the computationally efficient bit operators and provide a coarse measure of similarity. We demonstrate the utility of our algorithm using two common bioinformatics tasks: identifying data sets with similar gene expression profiles, and comparing annotated genomes. CONCLUSIONS: The BSF is a highly efficient pairwise similarity algorithm that can scale to billions of comparisons without the need for specialized hardware.