Using Genetics to Inform Interventions Related to Sodium and Potassium in Hypertension.

BACKGROUND: Hypertension is a key risk factor for major adverse cardiovascular events but remains difficult to treat in many individuals. Dietary interventions are an effective approach to lower blood pressure (BP) but are not equally effective across all individuals. BP is heritable, and genetics may be a useful tool to overcome treatment response heterogeneity. We investigated whether the genetics of BP could be used to identify individuals with hypertension who may receive a particular benefit from lowering sodium intake and boosting potassium levels. METHODS: In this observational genetic study, we leveraged cross-sectional data from up to 296 475 genotyped individuals drawn from the UK Biobank cohort for whom BP and urinary electrolytes (sodium and potassium), biomarkers of sodium and potassium intake, were measured. Biologically directed genetic scores for BP were constructed specifically among pathways related to sodium and potassium biology (pharmagenic enrichment scores), as well as unannotated genome-wide scores (conventional polygenic scores). We then tested whether there was a gene-by-environment interaction between urinary electrolytes and these genetic scores on BP. RESULTS: Genetic risk and urinary electrolytes both independently correlated with BP. However, urinary sodium was associated with a larger BP increase among individuals with higher genetic risk in sodium- and potassium-related pathways than in those with comparatively lower genetic risk. For example, each SD in urinary sodium was associated with a 1.47-mm Hg increase in systolic BP for those in the top 10% of the distribution of genetic risk in sodium and potassium transport pathways versus a 0.97-mm Hg systolic BP increase in the lowest 10% (P=1.95×10-3). This interaction with urinary sodium remained when considering estimated glomerular filtration rate and indexing sodium to urinary creatinine. There was no strong evidence of an interaction between urinary sodium and a standard genome-wide polygenic score of BP. CONCLUSIONS: The data suggest that genetic risk in sodium and potassium pathways could be used in a precision medicine model to direct interventions more specifically in the management of hypertension. Intervention studies are warranted.

Association Between Anesthesiologist Sex and Patients' Postoperative Outcomes: A Population-based Cohort Study.

OBJECTIVE: To examine the association of anesthesiologist sex on postoperative outcomes. BACKGROUND: Differences in patient postoperative outcomes exist, depending on whether the primary surgeon is male or female, with better outcomes seen among patients treated by female surgeons. Whether the intraoperative anesthesiologist's sex is associated with differential postoperative patient outcomes is unknown. METHODS: We performed a population-based, retrospective cohort study among adult patients undergoing one of 25 common elective or emergent surgical procedures from 2007 to 2019 in Ontario, Canada. We assessed the association between the sex of the intraoperative anesthesiologist and the primary end point of the adverse postoperative outcome, defined as death, readmission, or complication within 30 days after surgery, using generalized estimating equations. RESULTS: Among 1,165,711 patients treated by 3006 surgeons and 1477 anesthesiologists, 311,822 (26.7%) received care from a female anesthesiologist and 853,889 (73.3%) from a male anesthesiologist. Overall, 10.8% of patients experienced one or more adverse postoperative outcomes, of whom 1.1% died. Multivariable adjusted rates of the composite primary end point were higher among patients treated by male anesthesiologists (10.6%) compared with female anesthesiologists (10.4%; adjusted odds ratio 1.02, 95% CI: 1.00-1.05, P =0.048). CONCLUSIONS: We demonstrated a significant association between sex of the intraoperative anesthesiologist and patient short-term outcomes after surgery in a large cohort study. This study supports the growing literature of improved patient outcomes among female practitioners. The underlying mechanisms of why outcomes differ between male and female physicians remain elusive and require further in-depth study.

Exact Ansatz of Fermion-Boson Systems for a Quantum Device.

We present an exact Ansatz for the eigenstate problem of mixed fermion-boson systems that can be implemented on quantum devices. Based on a generalization of the electronic contracted Schrödinger equation (CSE), our approach guides a trial wave function to the ground state of any arbitrary mixed Hamiltonian by directly measuring residuals of the mixed CSE on a quantum device. Unlike density functional and coupled cluster theories applied to electron-phonon or electron-photon systems, the accuracy of our approach is not limited by the unknown exchange-correlation functional or the uncontrolled form of the exponential Ansatz. To test the performance of the method, we study the Tavis-Cummings model, commonly used in polaritonic quantum chemistry. Our results demonstrate that the CSE is a powerful tool in the development of quantum algorithms for solving general fermion-boson many-body problems.

Impact of Social Disparities on 5-Year Survival Rates in Pediatric Hematologic Malignancies.

BACKGROUND: Socioeconomic disparities exist in pediatric patients with hematologic malignancies, leading to suboptimal survival rates. Social determinants of health impact health outcomes, and in children, they may not only lead to worse survival outcomes but carry over into late effects in adult life. The social deprivation index (SDI) is a composite score using geographic county data to measure social determinants of health. Using the SDI, the purpose of the present study is to stratify survival outcomes in pediatric patients with hematologic malignancies based on area deprivation. METHODS: A retrospective cohort study was performed using the national Surveillance, Epidemiology, and End Results oncology registry in the USA from 1975 to 2016 based on county-level data. Pediatric patients (≤18 y old) with a diagnosis of leukemia or lymphoma based on the International Classification for Oncology, third edition (ICD-O-3) were used for inclusion criteria. Patients were grouped by cancer subtype for leukemia into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia while for lymphoma into non-Hodgkin's lymphoma and Hodgkin's lymphoma. SDI scores were calculated for each patient and divided into quartiles, with Q1 being the lowest area of deprivation and Q4 being the highest, respectively. RESULTS: A total of 38,318 leukemia and lymphoma patients were included. Quartile data demonstrated stratification in survival based on area deprivation for ALL, with no survival differences in the other cancer subtypes. Patients with ALL from the most deprived area had a roughly 3% difference in both overall and cancer-specific morality at 5 years compared with the least deprived area. CONCLUSION: Disparities in pediatric patients with ALL represent a significant area for quality improvement. Social programs may have value in improving survival outcomes and could rely on metrics such as SDI.

Inflammation-induced loss of CFTR-expressing airway ionocytes in non-eosinophilic asthma.

BACKGROUND AND OBJECTIVE: Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non-eosinophilic asthma. Non-eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non-eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non-eosinophilic asthma. METHODS: Patient-derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air-liquid interface. Single cell RNA-sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma. RESULTS: We identified that hBECs from patients with non-eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR-expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic-dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma-like inflammatory cytokine mixture led to a reduction in ionocytes. CONCLUSION: Inflammation-induced loss of CFTR-expressing ionocytes in airway cells from non-eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target.

Association of chronic kidney disease with postoperative outcomes: a national surgical quality improvement program (NSQIP) multi-specialty surgical cohort analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with higher incidence of major surgery. No studies have evaluated the association between preoperative kidney function and postoperative outcomes across a wide spectrum of procedures. We aimed to evaluate the association between CKD and 30-day postoperative outcomes across surgical specialties. METHODS: We selected adult patients undergoing surgery across eight specialties. The primary study endpoint was major complications, defined as death, unplanned reoperation, cardiac complication, or stroke within 30 days following surgery. Secondary outcomes included Clavien-Dindo high-grade complications, as well as cardiac, pulmonary, infectious, and thromboembolic complications. Multivariable regression was performed to evaluate the association between CKD and 30-day postoperative complications, adjusted for baseline characteristics, surgical specialty, and operative time. RESULTS: In total, 1,912,682 patients were included. The odds of major complications (adjusted odds ratio [aOR] 2.14 [95% confidence interval (CI): 2.07, 2.21]), death (aOR 3.03 [95% CI: 2.88, 3.19]), unplanned reoperation (aOR 1.57 [95% CI: 1.51, 1.64]), cardiac complication (aOR 3.51 [95% CI: 3.25, 3.80]), and stroke (aOR 1.89 [95% CI: 1.64, 2.17]) were greater for patients with CKD stage 5 vs. stage 1. A similar pattern was observed for the secondary endpoints. CONCLUSION: This population-based study demonstrates the negative impact of CKD on operative outcomes across a diverse range of procedures and patients.

Integration of EpiSign, facial phenotyping, and likelihood ratio interpretation of clinical abnormalities in the re-classification of an ARID1B missense variant.

Heterozygous ARID1B variants result in Coffin-Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to ARID1B loss of function variants. We report a boy with developmental delay, feeding difficulties, aspiration, recurrent respiratory infections, slow growth, and hypotonia without a clinical diagnosis, where a previously unreported ARID1B missense variant was classified as a variant of uncertain significance. The pathogenicity of this variant was refined through combined methodologies including genome-wide methylation signature analysis (EpiSign), Machine Learning (ML) facial phenotyping, and LIRICAL. Trio exome sequencing and EpiSign were performed. ML facial phenotyping compared facial images using FaceMatch and GestaltMatcher to syndrome-specific libraries to prioritize the trio exome bioinformatic pipeline gene list output. Phenotype-driven variant prioritization was performed with LIRICAL. A de novo heterozygous missense variant, ARID1B p.(Tyr1268His), was reported as a variant of uncertain significance. The ACMG classification was refined to likely pathogenic by a supportive methylation signature, ML facial phenotyping, and prioritization through LIRICAL. The ARID1B genotype-phenotype has been expanded through an extended analysis of missense variation through genome-wide methylation signatures, ML facial phenotyping, and likelihood-ratio gene prioritization.

Adjuvant immunotherapy in renal cell carcinoma: a systematic review and meta-analysis.

OBJECTIVES: To synthesise available data regarding the disease-free survival (DFS) benefit of adjuvant immune checkpoint inhibitors (ICIs) for patients with renal cell carcinoma (RCC) and evaluate the overall safety profile of ICIs in this setting. MATERIALS AND METHODS: We utilised PubMed, Embase, and relevant conference proceedings to identify phase III randomised controlled trials comparing adjuvant ICIs vs placebo/observation for RCC. The primary outcome of interest was DFS. Variables for subgroup analyses were programmed death-ligand 1 (PD-L1) expression, sarcomatoid features, nephrectomy type, and disease-risk category. Secondary outcomes included Grade ≥3 adverse events (AEs), immune-related AEs, and treatment discontinuation due to AEs. All outcomes were analysed using random-effects models owing to inter-study heterogeneity. RESULTS: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I2  = 64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.69-1.04) there was significant benefit among patients with positive PD-L1 expression (HR 0.72, 95% CI 0.55-0.94) and sarcomatoid features (HR 0.59, 95% CI 0.38-0.91). CONCLUSION: The evidence base to date regarding ICIs as adjuvant therapy in RCC is mixed - conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD-L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.

Glomerular hyperfiltration is an independent predictor of postoperative outcomes: A NSQIP multi-specialty surgical cohort analysis.

AIM: While high estimated glomerular filtration rate (eGFR) has been associated with increased overall mortality, its effect on postoperative outcomes is relatively understudied. We sought to investigate the association between high eGFR and 30-day postoperative outcomes using a multi-specialty surgical cohort. METHODS: Using the National Surgical Quality Improvement Program database, we selected adult for whom eGFR could be calculated using the 2021 Chronic Kidney Disease Epidemiology Collaboration equation. Based on sex-specific distributions of eGFR stratified by age quintiles, we classified patients into low (<5th percentile), normal (5-95th percentile) and high eGFR (>95th percentile). The primary outcome was a composite of any 30-day major adverse outcomes, including: death, reoperation, cardiac arrest, myocardial infarction and stroke. Secondary outcomes included 30-day infectious complications, venous thromboembolism (VTE), bleeding requiring transfusion, prolonged length of stay and unplanned readmission. After matching for demographic differences, comorbidity burden and operative characteristics, logistic regression models were used to evaluate the association between extremes of eGFR and the outcomes of interest. RESULTS: Of 1 668 447 patients, 84 115 (5.07%) had a high eGFR. High eGFR was not associated with major adverse outcomes (odds ratio [OR] 1.00 [95% confidence interval (CI): 0.97, 1.03]); however, it was associated with reoperation (OR 1.04 [95% CI: 1.00,1.08]), infectious complications (OR 1.14 [95% CI: 1.11, 1.16]), VTE (OR 1.15 [95% CI: 1.09, 1.22]) and prolonged length of stay (OR 1.19 [95% CI: 1.16, 1.21]). CONCLUSION: Our findings support an association between high eGFR and adverse 30-day postoperative outcomes.

The geriatric nutritional risk index predicts complications after nephrectomy for renal cancer.

PURPOSE: We examined if malnutrition, as defined by the Geriatric Nutritional Risk Index (GNRI), is independently associated with 30-day postoperative complications in patients undergoing nephrectomy for the treatment of renal cancer. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database from 2006-2019, we identified patients ≥65 years old who underwent nephrectomy for renal cancer. The following formula for GNRI was used to define preoperative nutritional status: 1.489 x serum albumin (g/L) + 41.7 x (current body weight [kg]/ ideal body weight [kg]). Based on the GNRI, patients were classified as having no (> 98), moderate (92-98), or severe malnutrition (< 92). After adjusting for potential confounders, multivariable logistic regression analyses were performed to assess the association between GNRI and 30-day postoperative complications. Odds ratios (OR) with 95% confidence intervals (CI) were reported. RESULTS: A total of 7,683 patients were identified, of which 1,241 (16.2%) and 872 (11.3%) had moderate and severe malnutrition, respectively. Compared to normal nutrition, moderate and severe malnutrition were significantly associated with a greater odds of superficial surgical site infection, progressive renal insufficiency, readmission, extended length of stay, and non-home discharge. Severe malnutrition was also associated with urinary tract infection (OR 2.10, 95% CI 1.31-3.35) and septic shock (OR 2.93, 95% CI 1.21-7.07). CONCLUSION: Malnutrition, as defined by a GNRI ≤ 98, is an independent predictor of 30-day complications following nephrectomy. The GNRI could be used to counsel elderly patients with renal cancer prior to nephrectomy.

Transcriptomic analysis reveals myometrial topologically associated domains linked to the onset of human term labour.

Changes in cell phenotype are thought to occur through the expression of groups of co-regulated genes within topologically associated domains (TADs). In this paper, we allocate genes expressed within the myometrium of the human uterus during the onset of term labour into TADs. Transformation of the myometrial cells of the uterus into a contractile phenotype during term human labour is the result of a complex interaction of different epigenomic and genomic layers. Recent work suggests that the transcription factor (TF) RELA lies at the top of this regulatory network. Using deep RNA sequencing (RNAseq) analysis of myometrial samples (n = 16) obtained at term from women undergoing caesarean section prior to or after the onset of labour, we have identified evidence for how other gene expression regulatory elements interact with TFs in the labour phenotype transition. Gene set enrichment analysis of our RNAseq data identified three modules of enriched genes (M1, M2 and M3), which in gene ontology studies are linked to matrix degradation, smooth muscle and immune gene signatures, respectively. These genes were predominantly located within chromosomal TADs suggesting co-regulation of expression. Our transcriptomic analysis also identified significant differences in the expression of long non-coding RNAs (lncRNA), microRNAs (miRNA) and TFs that were predicted to target genes within the TADs. Additionally, network analysis revealed 15 new lncRNA (MCM3AP-AS1, TUG1, MIR29B2CHG, HCG18, LINC00963, KCNQ1OT1, NEAT1, HELLPAR, SNHG16, NUTM2B-AS1, MALAT1, PSMA3-AS1, GABPB1-AS1, NORAD and NKILA) and 4 miRNA (mir-145, mir-223, mir-let-7a and mir-132) as top gene hubs with three TFs (NFKB1, RELA and ESR1) as master regulators. Together, these factors are likely to be involved in co-regulatory networks driving a myometrial transformation to generate an estrogen-sensitive phenotype. We conclude that lncRNA and miRNA targeting the estrogen receptor 1 and nuclear factor kappa B pathways play a key role in the initiation of human labour. For the first time, we perform an integrative analysis to present a multi-level genomic signature made of mRNA, non-coding RNA and TFs in the myometrium for spontaneous term labour.

The Geriatric Nutritional Risk Index Predicts Postoperative Outcomes in Bladder Cancer: A Propensity Score-Matched Analysis.

PURPOSE: The Geriatric Nutritional Risk Index (GNRI) is a simple screening tool to predict nutrition-related risk of morbidity and mortality in older patients. We assessed whether preoperative GNRI was associated with 30-day complications after radical cystectomy (RC). MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified patients 65 years or older who underwent RC for the treatment of bladder cancer between 2007 and 2019. Patients were dichotomized into at-risk (GNRI ≤98) or no-risk (GNRI >98) groups. Using propensity score matching, the 2 groups were compared for baseline differences and 30-day outcomes. We evaluated GNRI as an independent predictor of postoperative complications using multivariable logistic regression analysis. RESULTS: We identified 2,926 patients eligible for analysis. After propensity score matching, patients in the at-risk GNRI group had higher rates of any complication (p=0.017), blood transfusion (p=0.002), extended length of stay (p=0.004) and nonhome discharge (p <0.001). Multivariable logistic regression analysis revealed that a decreasing GNRI is an independent prognostic factor for mortality (OR 1.05, 95% CI 1.01-1.08, p=0.009), blood transfusion (OR 1.03, 95% CI 1.02-1.04, p <0.001), pneumonia (OR 1.04, 95% CI 1.01-1.07, p=0.013), extended length of stay (OR 1.03, 95% CI 1.02-1.05, p <0.001) and nonhome discharge (OR 1.04, 95% CI 1.03-1.06, p <0.001). CONCLUSIONS: We demonstrate that nutritional status evaluated by GNRI predicts 30-day complications after RC.

Excitations of Quantum Many-Body Systems via Purified Ensembles: A Unitary-Coupled-Cluster-Based Approach.

State-average calculations based on a mixture of states are increasingly being exploited across chemistry and physics as versatile procedures for addressing excitations of quantum many-body systems. If not too many states should need to be addressed, calculations performed on individual states are also a common option. Here we show how the two approaches can be merged into one method, dealing with a generalized yet single pure state. Implications in electronic structure calculations are discussed and for quantum computations are pointed out.

An altered sputum macrophage transcriptome contributes to the neutrophilic asthma endotype.

BACKGROUND: Neutrophilic asthma (NA) is a clinically important asthma phenotype, the cellular and molecular basis of which is not completely understood. Airway macrophages are long-lived immune cells that exert important homeostatic and inflammatory functions which are dysregulated in asthma. Unique transcriptomic programmes reflect varied macrophage phenotypes in vitro. We aimed to determine whether airway macrophages are transcriptomically altered in NA. METHODS: We performed RNASeq analysis on flow cytometry-isolated sputum macrophages comparing NA (n = 7) and non-neutrophilic asthma (NNA, n = 13). qPCR validation of RNASeq results was performed (NA n = 13, NNA n = 23). Pathway analysis (PANTHER, STRING) of differentially expressed genes (DEGs) was performed. Gene set variation analysis (GSVA) was used to test for enrichment of NA macrophage transcriptomic signatures in whole sputum microarray (cohort 1 - controls n = 16, NA n = 29, NNA n = 37; cohort 2 U-BIOPRED - controls n = 16, NA n = 47, NNA n = 57). RESULTS: Flow cytometry-sorting significantly enriched sputum macrophages (99.4% post-sort, 44.9% pre-sort, p < .05). RNASeq analysis confirmed macrophage purity and identified DEGs in NA macrophages. Selected DEGs (SLAMF7, DYSF, GPR183, CSF3, PI3, CCR7, all p < .05 NA vs. NNA) were confirmed by qPCR. Pathway analysis of NA macrophage DEGs was consistent with responses to bacteria, contribution to neutrophil recruitment and increased expression of phagocytosis and efferocytosis factors. GSVA demonstrated neutrophilic macrophage gene signatures were significantly enriched in whole sputum microarray in NA vs. NNA and controls in both cohorts. CONCLUSIONS: We demonstrate a pathophysiologically relevant sputum macrophage transcriptomic programme in NA. The finding that there is transcriptional activation of inflammatory programmes in cell types other than neutrophils supports the concept of NA as a specific endotype.

Preterm labor is a distinct process from term labor following computational analysis of human myometrium.

BACKGROUND: The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor. OBJECTIVE: This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures. STUDY DESIGN: Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n=31), term labor (n=13), preterm not in labor (n=21), preterm labor with acute clinical chorioamnionitis (n=6), preterm labor with no acute clinical chorioamnionitis (n=9), twin preterm not in labor (n=8), and twin preterm labor with no acute clinical chorioamnionitis (n=5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis. RESULTS: Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term not-in-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity. CONCLUSION: The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.

An Exploration of Sedentary Behavior Patterns in Community-Dwelling People With Stroke: A Cluster-Based Analysis.

BACKGROUND AND PURPOSE: Long periods of daily sedentary time, particularly accumulated in long uninterrupted bouts, are a risk factor for cardiovascular disease. People with stroke are at high risk of recurrent events and prolonged sedentary time may increase this risk. We aimed to explore how people with stroke distribute their periods of sedentary behavior, which factors influence this distribution, and whether sedentary behavior clusters can be distinguished? METHODS: This was a secondary analysis of original accelerometry data from adults with stroke living in the community. We conducted data-driven clustering analyses to identify unique accumulation patterns of sedentary time across participants, followed by multinomial logistical regression to determine the association between the clusters, and the total amount of sedentary time, age, gender, body mass index (BMI), walking speed, and wake time. RESULTS: Participants in the highest quartile of total sedentary time accumulated a significantly higher proportion of their sedentary time in prolonged bouts (P < 0.001). Six unique accumulation patterns were identified, all of which were characterized by high sedentary time. Total sedentary time, age, gender, BMI, and walking speed were significantly associated with the probability of a person being in a specific accumulation pattern cluster, P < 0.001 - P = 0.002. DISCUSSION AND CONCLUSIONS: Although unique accumulation patterns were identified, there is not just one accumulation pattern for high sedentary time. This suggests that interventions to reduce sedentary time must be individually tailored.Video Abstract available for more insight from the authors (see the Video Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A343).

Reduced Density Matrix Functional Theory for Bosons.

Based on a generalization of Hohenberg-Kohn's theorem, we propose a ground state theory for bosonic quantum systems. Since it involves the one-particle reduced density matrix γ as a variable but still recovers quantum correlations in an exact way it is particularly well suited for the accurate description of Bose-Einstein condensates. As a proof of principle we study the building block of optical lattices. The solution of the underlying v-representability problem is found and its peculiar form identifies the constrained search formalism as the ideal starting point for constructing accurate functional approximations: The exact functionals F[γ] for this N-boson Hubbard dimer and general Bogoliubov-approximated systems are determined. For Bose-Einstein condensates with N_{BEC}≈N condensed bosons, the respective gradient forces are found to diverge, ∇_{γ}F∝1/sqrt[1-N_{BEC}/N], providing a comprehensive explanation for the absence of complete condensation in nature.

Seroprevalence and Risk Factors Possibly Associated with Emerging Zoonotic Vaccinia Virus in a Farming Community, Colombia.

In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.

Circulating microvesicles are less procoagulant and carry different miRNA cargo in myelodysplasia.

BACKGROUND AND AIMS: Myelodysplasia (MDS) is characterised by abnormal haematopoiesis and increased risk of bleeding. Microvesicles (MV) play a key role in coagulation and their impact in MDS is unknown. METHODS: Platelet free plasma from 35 red-cell transfusion-dependent MDS patients and 15 controls were analysed. Pro-coagulant function was assessed by the XaCT assay and by thrombin generation (ETP). Total MV were enumerated by nano-tracking analysis. MV subsets were quantified by flow cytometry after staining with specific antibodies for various endovascular cell types. Small RNA was quantitated and sequenced. The MV measurements were correlated with MDS clinical risk scores and level of transfusion dependence. RESULTS: The pro-coagulant function of MV was significantly lower in MDS. All the MV subtypes, as measured by flow cytometric markers, were also significantly lower. The small RNA and miRNA cargo were significantly higher in MDS. The miRNA profile showed that mir-28 and mir-LETD7 were under expressed whilst mir-584J and mir-4485 were over expressed in MV from MDS. CONCLUSIONS: Circulating MV in MDS show reduced pro-coagulant functional activity, reduced subtypes by flow cytometry and significantly different miRNA content. However, the levels or subtypes of MV did not predict the clinical phenotype or level of transfusion dependence.

On the time evolution of fermionic occupation numbers.

We derive an approximate equation for the time evolution of the natural occupation numbers for fermionic systems. The evolution of such numbers is connected with the symmetry-adapted generalized Pauli exclusion principle, as well as with the evolution of the natural orbitals and a set of many-body relative phases. We then relate the evolution of these phases to a geometrical and a dynamical term attached to some of the Slater determinants appearing in the configuration-interaction expansion of the wave function. Our approach becomes exact for highly symmetric systems whenever the wave function possesses as many Slater determinants as independent occupation numbers.