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Background: Incidence of methicillin-sensitive Staphylococcus aureus (MSSA) bloodstream infections (BSIs) in the United States during 2012–2017 has been reported to have been stable for hospital-onset BSIs and to have increased 3.9% per year for community-onset BSIs. We sought to determine whether these trends continued in more recent years and whether there were further differences within subgroups of community-onset BSIs. Methods: We analyzed CDC Emerging Infections Program active, population- and laboratory-based surveillance data during 2016–2019 for MSSA BSIs from 8 counties in 5 states. BSI cases were defined as isolation of MSSA from blood in a surveillance area resident. Cases were considered hospital onset (HO) if culture was obtained >3 days after hospital admission and healthcare-associated community-onset (HACO) if culture was obtained on or after day 3 of hospitalization and was associated with dialysis, hospitalization, surgery, or long-term care facility residence within 1 year prior or if a central venous catheter was present ≤2 days prior. Cases were otherwise considered community-associated (CA). Annual rates per 100,000 census population were calculated for each epidemiologic classification; rates of HACO cases among chronic dialysis patients per 100,000 dialysis patients were calculated using US Renal Data System data. Annual increases were modeled using negative binomial or Poisson regression and accounting for changes in the overall population age group, and sex. Descriptive analyses were performed. Results: Overall, 8,344 MSSA BSI cases were reported. From 2016–2019 total MSSA BSI rates increased from 23.9 per 100,000 to 28.5 per 100,000 (6.6% per year; P < .01). MSSA BSI rates also increased significantly among all epidemiologic classes. HO cases increased from 2.5 per 100,000 to 3.2 per 100,000 (7.9% per year; P = .01). HACO cases increased from 12.7 per 100,000 to 14.7 per 100,000 (7.0% per year; P = .01). CA cases increased from 8.4 per 100,000 to 10.4 per 100,000 (6.7% per year; P < .01) (Fig. 1). Significant increases in MSSA BSI rates were also observed for nondialysis HACO cases (9.3 per 100,000 to 11.1 per 100,000; 7.8% per year; P < .01) but not dialysis HACO cases (1,823.2 per 100,000 to 1,857.4 per 100,000; 1.4% per year; P = .59). Healthcare risk factors for HACO cases were hospitalization in the previous year (82%), surgery (31%), dialysis (27%), and long-term care facility residence (19%). Conclusions: MSSA BSI rates increased from 2016–2019 overall, among all epidemiologic classes, and among nondialysis HACO cases. Efforts to prevent MSSA BSIs among individuals with healthcare risk factors, particularly those related to hospitalization, might have an impact on MSSA BSI rates.
Microfoundations allow the unpacking of processes by which dynamic capabilities are created. Along this line, managerial cognition has been proposed as a variable related to the dynamic capabilities. However, the high number of cognitive variables reported hinders the theoretical contributions. Thus, this study classifies the managerial cognitive variables of chief executive officers (CEOs) into three types of dynamic managerial capabilities: (1) managerial sensing, (2) managerial seizing, and (3) managerial reconfiguration. We estimate the correlation of these managerial capabilities with firms' dynamic capabilities. We use a three-level random effects model to synthesize 101 correlations reported from 2007 to 2021, representing 6,153 CEOs around the world. This meta-analysis reveals a positive relationship between CEOs' managerial cognition and dynamic capabilities, especially with respect to those cognitive variables that support managerial sensing as the perception of opportunities and entrepreneurial alertness.
Higher inflammation has been linked to poor physical and mental health outcomes, and mortality, but few studies have rigorously examined whether changes in perceived stress and depressive symptoms are associated with increased inflammation within family caregivers and non-caregivers in a longitudinal design.
REasons for Geographic And Racial Differences in Stroke cohort study.
Participants included 239 individuals who were not caregivers at baseline but transitioned to providing substantial and sustained caregiving over time. They were initially matched to 241 non-caregiver comparisons on age, sex, race, education, marital status, self-rated health, and history of cardiovascular disease. Blood was drawn at baseline and approximately 9.3 years at follow-up for both groups.
Perceived Stress Scale, Center for Epidemiological Studies-Depression, inflammatory biomarkers, including high-sensitivity C-reactive protein, D dimer, tumor necrosis factor alpha receptor 1, interleukin (IL)-2, IL-6, and IL-10 taken at baseline and follow-up.
Although at follow-up, caregivers showed significantly greater worsening in perceived stress and depressive symptoms compared to non-caregivers, there were few significant associations between depressive symptoms or perceived stress on inflammation for either group. Inflammation, however, was associated with multiple demographic and health variables, including age, race, obesity, and use of medications for hypertension and diabetes for caregivers and non-caregivers.
These findings illustrate the complexity of studying the associations between stress, depressive symptoms, and inflammation in older adults, where these associations may depend on demographic, disease, and medication effects. Future studies should examine whether resilience factors may prevent increased inflammation in older caregivers.
We propose here a method to experimentally quantify unsteady leading-edge flow separation on aerofoils with finite thickness. The methodology relies on the computation of a leading-edge suction parameter based on measured values of the partial circulation around the leading edge and the stagnation point location. We validate the computation of the leading-edge suction parameter for both numerical and experimental data under steady and unsteady flow conditions. The leading-order approximation of the definition of the leading-edge suction parameter is proven to be sufficiently accurate for the application to thin aerofoils such as the NACA0009 without a priori knowledge of the stagnation point location. The higher-order terms including the stagnation point location are required to reliably compute the leading-edge suction parameter on thicker aerofoils such as the NACA0015. The computation of the leading-edge suction parameter from inviscid flow theory does not assume the Kutta condition to be valid at the trailing edge which allows us to compute its value for separated flows. The relation between the leading-edge suction parameter and the evolution of the shear layer height is studied in two different unsteady flow conditions, a fixed aerofoil in a fluctuating free-stream velocity and a pitching aerofoil in a steady free stream. We demonstrate here that the instantaneous value of the leading-edge suction parameter based on the partial circulation around the leading edge is unambiguously defined for a given flow field and can serve as a directly quantitative measure of the degree of unsteady flow separation at the leading edge.
Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
Adverse drug reactions (ADRs) are associated with increased morbidity, mortality, and resource utilization. Drug interactions (DDIs) are among the most common causes of ADRs, and estimates have cited that up to 22% of patients take interacting medications. DDIs are often due to the propensity for agents to induce or inhibit enzymes responsible for the metabolism of concomitantly administered drugs. However, this phenomenon is further complicated by genetic variants of such enzymes. The aim of this study is to quantify and describe potential drug-drug, drug-gene, and drug-drug-gene interactions in a community-based patient population.
A regional pharmacy with retail outlets in Arkansas provided deidentified prescription data from March 2020 for 4761 individuals. Drug-drug and drug-drug-gene interactions were assessed utilizing the logic incorporated into GenMedPro, a commercially available digital gene-drug interaction software program that incorporates variants of 9 pharmacokinetic (PK) and 2 pharmacodynamic (PD) genes to evaluate DDIs and drug-gene interactions. The data were first assessed for composite drug-drug interaction risk, and each individual was stratified to a risk category using the logic incorporated in GenMedPro. To calculate the frequency of potential drug-gene interactions, genotypes were imputed and allocated to the cohort according to each gene’s frequency in the general population. Potential genotypes were randomly allocated to the population 100 times in a Monte Carlo simulation. Potential drug-drug, gene-drug, or gene-drug-drug interaction risk was characterized as minor, moderate, or major.
Based on prescription data only, the probability of a DDI of any impact (mild, moderate, or major) was 26% [95% CI: 0.248-0.272] in the population. This probability increased to 49.6% [95% CI: 0.484-0.507] when simulated genetic polymorphisms were additionally assessed. When assessing only major impact interactions, there was a 7.8% [95% CI: 0.070-0.085] probability of drug-drug interactions and 10.1% [95% CI: 0.095-0.108] probability with the addition of genetic contributions. The probability of drug-drug-gene interactions of any impact was correlated with the number of prescribed medications, with an approximate probability of 77%, 85%, and 94% in patients prescribed 5, 6, or 7+ medications, respectively. When stratified by specific drug class, antidepressants (19.5%), antiemetics (21.4%), analgesics (16%), antipsychotics (15.6%), and antiparasitics (49.7%) had the highest probability of major drug-drug-gene interaction.
In a community-based population of outpatients, the probability of drug-drug interaction risk increases when genetic polymorphisms are attributed to the population. These data suggest that pharmacogenetic testing may be useful in predicting drug interactions, drug-gene interactions, and severity of interactions when proactively evaluating patient medication profiles.
The dwarf planet Ceres has unique geomorphology, different from airless silicate objects like the Moon or asteroid Vesta, but also different from the icy outer planet satellites. All four primary planetary geologic processes [impact cratering, tectonism, volcanism, and gradation (weathering, erosion, and deposition of loose material)] are visible on Ceres’ surface. Ceres’ low albedo, heavily cratered surface displays craters <300 km in diameter, in which the lack of larger, multi-ring basins suggests resurfacing event(s) early in the dwarf planet’s history. Ejecta blankets in the youngest craters display bluish ejecta and rays, and lobate deposits in and around craters suggest impact slurries, ice-rich landslides, or cryovolcanic flows. Some landslides have exposed water ice, in less than a dozen locations on the surface. Tectonic features include impact-induced secondary crater chains and non-impact-related pit chains and fractures. Several impact craters have heavily fractured floors akin to those on the Moon. The distinctive mountain Ahuna Mons appears to be a cryovolcanic edifice, composed of a viscous, salt-rich, carbonate-bearing material. Ceres distinctive bright spots, Cerealia and Vinalia Faculae within Occator crater, are composed of salt-rich liquids containing carbonates, and were likely emplaced by some combination of deep brines extrusion and hydrothermal (shallow brines) processes.
We present the case of a 4-month-old, former 23-week premature baby who underwent patent ductus arteriosus device closure in the cardiac catheterisation lab with an Amplatzer Piccolo™ device at 12 weeks of life. This was complicated by late migration of the device into the aorta resulting in severe obstruction and requiring surgical intervention.
CHD is an important phenotypic feature of chromosome 22q11.2 copy number variants. Biventricular repair is usually possible, however there are rare reports of patients with chromosome 22q copy number variants and functional single ventricle cardiac disease.
This is a single centre retrospective review of patients with chromosome 22q copy number variants who underwent staged single ventricle reconstructive surgery between 1 July, 1984 and 31 December, 2020.
Seventeen patients met inclusion criteria. The most common diagnosis was hypoplastic left heart syndrome (n = 8) and vascular anomalies were present in 13 patients. A microdeletion of the chromosome 22 A-D low-copy repeat was present in 13 patients, and the remaining had a duplication. About half of the patients had documented craniofacial abnormalities and/or hypocalcaemia, and developmental delay was very common. Fifteen patients had a Norwood operation, 10 patients had a superior cavopulmonary anastomosis, and 7 patients had a Fontan. Two patients had cardiac transplantation after Fontan. Overall survival is 64% at 1 year, and 58% at 5 and 10 years. Most deaths occurred following Norwood operation (n = 5).
CHD necessitating single ventricle reconstruction associated with chromosome 22q copy number variants is not common, but typically occurs as a variant of hypoplastic left heart syndrome with the usual cytogenetic microdeletion. The most common neonatal surgical intervention performed is the Norwood, where most of the mortality burden occurs. Associated anomalies and medical issues may cause additional morbidity after cardiac surgery, but survival is similar to infants with other types of single ventricle disease.
Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood.
We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18–76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology.
The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32–16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3–36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases.
Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.
CEO social capital has shown a positive association with dynamic capabilities, although correlations have considerable heterogeneity among them. This meta-analysis estimates the correlation between CEO social capital and dynamic capabilities, and analyses moderator variables in explaining the heterogeneity in the results. Moderators are classified across four levels from macro to micro variables: country variables, firm environment, firm characteristics, and CEO variables. We apply a systematic search for studies in the Web of Science, Scopus, EBSCO, ProQuest, and Google Scholar databases. Additionally, we used a three-level random-effect meta-analysis on 89 correlations published between 2008 and 2021 from 9,272 CEOs. Findings indicate a positive correlation between CEO social capital and dynamic capabilities. Furthermore, we identified a moderator effect in the country and firm environment level. We found that the country of the study, the perception of transparency and legality in the country, and the environmental dynamism in the market moderate the size of the correlations. We also reject other moderators, including the individualism-collectivism national culture, firm size, the sources of social capital (business or political ties), and the dimension of the social capital (structural, relational or cognitive). This study contributes to the exploration of the sources of dynamic capabilities from the micro-foundation, identifies moderator variables that explain the heterogeneity in the results, and highlights the social nature of management activities which always evolve in a social context.
Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.
Praziquantel (PZQ) remains the only drug of choice for the treatment of schistosomiasis, caused by parasitic flatworms. The widespread use of PZQ in schistosomiasis endemic areas for about four decades raises concerns about the emergence of resistance of Schistosoma spp. to PZQ under drug selection pressure. This reinforces the urgency in finding alternative therapeutic options that could replace or complement PZQ. We explored the potential of medicinal plants commonly used by indigenes in Kenya for the treatment of various ailments including malaria, pneumonia, and diarrhoea for their antischistosomal properties. Employing the Soxhlet extraction method with different solvents, seven medicinal plants Artemisia annua, Ajuga remota, Bredilia micranta, Cordia africana, Physalis peruviana, Prunus africana and Senna didymobotrya were extracted. Qualitative phytochemical screening was performed to determine the presence of various phytochemicals in the plant extracts. Extracts were tested against Schistosoma mansoni newly transformed schistosomula (NTS) and adult worms and the schistosomicidal activity was determined by using the adenosine triphosphate quantitation assay. Phytochemical analysis of the extracts showed different classes of compounds such as alkaloids, tannins, terpenes, etc., in plant extracts active against S. mansoni worms. Seven extracts out of 22 resulted in <20% viability against NTS in 24 h at 100 μg/ml. Five of the extracts with inhibitory activity against NTS showed >69.7% and ≥72.4% reduction in viability against adult worms after exposure for 24 and 48 h, respectively. This study provides encouraging preliminary evidence that extracts of Kenyan medicinal plants deserve further study as potential alternative therapeutics that may form the basis for the development of the new treatments for schistosomiasis.
A national survey characterized training and career development for translational researchers through Clinical and Translational Science Award (CTSA) T32/TL1 programs. This report summarizes program goals, trainee characteristics, and mentorship practices.
A web link to a voluntary survey was emailed to 51 active TL1 program directors and administrators. Descriptive analyses were performed on aggregate data. Qualitative data analysis used open coding of text followed by an axial coding strategy based on the grounded theory approach.
Fifty out of 51 (98%) invited CTSA hubs responded. Training program goals were aligned with the CTSA mission. The trainee population consisted of predoctoral students (50%), postdoctoral fellows (30%), and health professional students in short-term (11%) or year-out (9%) research training. Forty percent of TL1 programs support both predoctoral and postdoctoral trainees. Trainees are diverse by academic affiliation, mostly from medicine, engineering, public health, non-health sciences, pharmacy, and nursing. Mentor training is offered by most programs, but mandatory at less than one-third of them. Most mentoring teams consist of two or more mentors.
CTSA TL1 programs are distinct from other NIH-funded training programs in their focus on clinical and translational research, cross-disciplinary approaches, emphasis on team science, and integration of multiple trainee types. Trainees in nearly all TL1 programs were engaged in all phases of translational research (preclinical, clinical, implementation, public health), suggesting that the CTSA TL1 program is meeting the mandate of NCATS to provide training to develop the clinical and translational research workforce.