Search

Aim: Elevated C‐reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity. Materials and Methods: This cross‐sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline. Linear regression models explored the extent to which CRP concentrations were elevated in each condition, unadjusted; adjusted for sociodemographic confounders and lifestyle and body mass index (BMI) in a series of models; or adjusted for BMI and waist circumference together or for adiposity alone. Results: After exclusion of participants with a potential acute infection at baseline, we tested the association in 292 772 UK Biobank participants. Linear regression showed that elevated CRP concentration was associated with all included conditions. After adjustment for sociodemographic confounders, lifestyle and BMI, chronic kidney disease, heart failure, liver disease, psoriasis, rheumatoid arthritis and chronic obstructive pulmonary disease were still associated with elevated CRP. In contrast, the association between prevalent diabetes, prior myocardial infarction (MI), hypertension and sleep apnoea and CRP could be mostly explained by adiposity alone. For example, the 42% higher CRP concentrations in diabetes compared to those without diabetes in the unadjusted model (lnCRP β: 0.35; 95% confidence interval [CI]: 0.32–0.37, p < 0.001) were completely attenuated after adjustment for BMI (lnCRP β: −0.07; 95% CI: −0.09−0.05, p < 0.001). Conclusions/Interpretation: In diabetes, MI, hypertension and sleep apnoea and elevated CRP appears to be accounted for by the greater adiposity typically evident in these conditions. However, for the other conditions, systemic inflammation cannot be explained by excess adiposity alone. [ABSTRACT FROM AUTHOR]

Public authority addresses how actors, ranging from officials to gang leaders, and cultural innovators, interact via cooperation, competition and conflict to generate shifting degrees of social order within territories. This paper summarises four key components that directly relate to power. First, power underlies public authority. Second, public authority entails and engenders institutional bricolage. Third, public authorities utilise functions, structures, ideas and symbols of statehood. Fourth, public authorities seek legitimacy. A systematic exposition of power informs analysing public authority—notably the degree to which it facilitates inclusive or exclusive participation and distribution of benefits. This paper outlines a conceptual framework, with attention to basic elements of power, using a triadic approach that incorporates seven basic formats (or strategic templates) for exercising such power. This framework can inform subsequent inquiry and policy analysis. [ABSTRACT FROM AUTHOR]

Background: Recently, a data‐driven regression analysis method was developed to utilize the resting‐state (rs) blood oxygenation level–dependent signal for cerebrovascular reactivity (CVR) mapping (rs‐CVR), which was previously optimized by comparing with the CO2 inhalation‐based method in health subjects and patients with neurovascular diseases. Purpose: To investigate the agreement of rs‐CVR and the CVR mapping with breath‐hold MRI (bh‐CVR) in patients with gliomas. Study Type: Retrospective. Population: Twenty‐five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas. Field Strength/Sequence: Dynamic T2*‐weighted gradient‐echo echo‐planar imaging during a breath‐hold paradigm and during the rs on a 3‐T scanner. Assessment: rs‐CVR with various frequency ranges and resting‐state fluctuation amplitude (RSFA) were assessed. The agreement between each rs‐based CVR measurement and bh‐CVR was determined by voxel‐wise correlation and Dice coefficient in the whole brain, gray matter, and the lesion region of interest (ROI). Statistical Tests: Voxel‐wise Pearson correlation, Dice coefficient, Fisher Z‐transformation, repeated‐measure analysis of variance and post hoc test with Bonferroni correction, and nonparametric repeated‐measure Friedman test and post hoc test with Bonferroni correction were used. Significance was set at P < 0.05. Results: Compared with bh‐CVR, the highest correlations were found at the frequency bands of 0.04–0.08 Hz and 0.02–0.04 Hz for rs‐CVR in both whole brain and the lesion ROI. RSFA had significantly lower correlations than did rs‐CVR of 0.02–0.04 Hz and a wider frequency range (0–0.1164 Hz). Significantly higher correlations and Dice coefficient were found in normal tissues than in the lesion ROI for all three methods. Data Conclusion: The optimal frequency ranges for rs‐CVR are determined by comparing with bh‐CVR in patients with gliomas. The rs‐CVR method outperformed the RSFA. Significantly higher correlation and Dice coefficient between rs‐ and bh‐CVR were found in normal tissue than in the lesion. Level of Evidence: 3 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Background: Sarcopenia often co‐occurs with osteoporosis in cross‐sectional studies. However, this association has rarely been studied in prospective studies. This study aimed to investigate the association between sarcopenia categories—along with its individual components—and incident osteoporosis in both middle‐aged and older men and women from the UK Biobank study. Methods: A total of 168,682 participants (48.8% women, aged 37 to 70 years at baseline) were included in this prospective study. Categories of sarcopenia (pre‐sarcopenia and sarcopenia), and its individual components, were defined according to the EWGSOP2 criteria (2019). Associations with incident osteoporosis by sex were investigated using Cox‐proportional hazard models adjusted for socio‐demographic, lifestyle and health‐related factors, and morbidity count. Associations between categories of sarcopenia and incident osteoporosis were also investigated by age‐groups and subtype of osteoporosis (with and without pathological fractures). Results: After a median follow‐up of 7.4 years, 6296 participants were diagnosed with osteoporosis. When the analyses were adjusted for a range of relevant confounding factors, pre‐sarcopenia was associated with 1.3‐times higher risk of osteoporosis in men (HR: 1.30 [95% CI: 1.03 to 1.63]) but not in women, and sarcopenia was associated with 1.66‐times increased osteoporosis risk in women (HR: 1.66 [95% CI: 1.33 to 2.08]) but not in men compared with people without sarcopenia or pre‐sarcopenia. A similar magnitude of associations was found in osteoporosis without pathological fractures but weaker for those with pathological fractures. Within the individual components, low muscle mass (HRwomen: 1.36 [95% CI: 1.22 to 1.51] and HRmen: 3.07 [95% CI: 1.68 to 5.59]), followed by slow gait speed (HRwomen: 1.30 [95% CI: 1.17 to 1.45] and HRmen: 1.70 [95% CI: 1.43 to 2.02]), were associated with a higher risk of incident osteoporosis in both sexes. Low grip strength was associated with a higher risk of incident osteoporosis in men (HR: 1.38 [95% CI: 1.15 to 1.65]), but not in women. No significant interaction between the exposures and incident osteoporosis by age groups were identified. Conclusions: Our findings demonstrated that pre‐sarcopenic men and sarcopenic women had a higher risk of developing osteoporosis even after adjustment for a large range of potential confounders. Considering that sarcopenia could be prevented, health interventions to improve physical capability may delay or prevent the onset of osteoporosis. [ABSTRACT FROM AUTHOR]

Music has been a therapeutic strategy proposed to improve impaired movement performance, but there remains a lack of understanding of how music impacts motor cortical activity. Thus, the purpose of this study is to use a time–frequency analysis (i.e., wavelet) of electroencephalographic (EEG) data to determine differences in motor and auditory cortical activity when moving to music at two different rates. Twenty healthy young adults tapped their index finger while electroencephalography was collected. There were three conditions (tapping in time with a tone and with two contrasting music styles), and each condition was repeated at two different rates (70 and 140 beats per minute). A time–frequency Morlet wavelet analysis was completed for electrodes of interest over the sensorimotor areas (FC3, FC4, FCz, C3, C4, Cz) and the primary auditory areas (T7, T8). Cluster‐based permutation testing was applied to the electrodes of interest for all conditions. Results showed few differences between cortical oscillations when moving to music versus a tone. However, the two music conditions elicited a variety of distinct responses, particularly at the slower movement rate. These results suggest that music style and movement rate should be considered when designing therapeutic applications that include music to target motor performance. [ABSTRACT FROM AUTHOR]

Human learning, at least in part, appears to be dependent on the evaluation of how outcomes of our actions align with our expectations. Over the past 23 years, electroencephalography (EEG) has been used to probe the neural signatures of feedback processing. Seminal work demonstrated a difference in the human event‐related potential (ERP) dependent on whether people were processing correct or incorrect feedback. Since then, these feedback evoked ERPs have been associated with reinforcement learning and conflict monitoring, tied to subsequent behavioral adaptations, and shown to be sensitive to a wide range of factors (e.g., Parkinson's disease). Recently, research has turned to frequency decomposition techniques to examine how changes in the EEG power spectra are related to underlying learning mechanisms. Although the literature on the neural correlates of feedback processing is vast, there are still methodological discrepancies and differences in results across studies. Here, we provide reference results and an investigation of methodological considerations for the ERP (reward positivity) and frequency (delta and theta power) correlates of feedback evaluation with a large sample size. Specifically, participants (n = 500) performed a two‐armed bandit task while we recorded EEG. Our findings provide key information about the data characteristics and relationships that exist between the neural signatures of feedback evaluation. Additionally, we conclude with selected methodological recommendations for standardization of future research. All data and scripts are freely provided to facilitate open science. While there is an abundance of EEG research probing the neural basis of feedback evaluation, there are differences in results and no consensus on methods across studies. We sought to resolve these issues in a large sample study (n = 500). Our findings provide reference data to inform future research into the EEG correlates of feedback processing, reconcile the relationship between the ERP and frequency correlates of feedback processing, and detail selected methodological guidelines for analysis. [ABSTRACT FROM AUTHOR]

Purpose: Resting‐state functional MRI (rs‐FMRI) has shown potential for presurgical mapping of eloquent cortex when a patient's performance on task‐based FMRI is compromised. The seed‐based analysis is a practical approach for detecting rs‐FMRI functional networks; however, seed localization remains challenging for presurgical language mapping. Therefore, we proposed a data‐driven approach to guide seed localization for presurgical rs‐FMRI language mapping. Methods: Twenty‐six patients with brain tumors located in left perisylvian regions had undergone task‐based FMRI and rs‐FMRI before tumor resection. For the seed‐based rs‐FMRI language mapping, a seeding approach that integrates regional homogeneity and meta‐analysis maps (RH+MA) was proposed to guide the seed localization. Canonical and task‐based seeding approaches were used for comparison. The performance of the 3 seeding approaches was evaluated by calculating the Dice coefficients between each rs‐FMRI language mapping result and the result from task‐based FMRI. Results: With the RH+MA approach, selecting among the top 6 seed candidates resulted in the highest Dice coefficient for 81% of patients (21 of 26) and the top 9 seed candidates for 92% of patients (24 of 26). The RH+MA approach yielded rs‐FMRI language mapping results that were in greater agreement with the results of task‐based FMRI, with significantly higher Dice coefficients (P <.05) than that of canonical and task‐based approaches within putative language regions. Conclusion: The proposed RH+MA approach outperformed the canonical and task‐based seed localization for rs‐FMRI language mapping. The results suggest that RH+MA is a robust and feasible method for seed‐based functional connectivity mapping in clinical practice. [ABSTRACT FROM AUTHOR]

While most strategic group research has focused on performance implications, we consider the relationship between strategic group membership and reputation. Using strategic group identity and domain consensus concepts, we propose strategic groups have different reputations. We find significant differences exist in reputation across three identified strategic groups of U.S. property/casualty insurers, supporting our contention that reputation is a multilevel concept. Post hoc analyses suggest strategic groups with higher reputation also have higher performance on some critical measures, indicating reputation may be a mobility barrier beneficial to members of certain groups. Practitioner implications include challenges of within-group differentiation in firm reputation. [ABSTRACT FROM AUTHOR]

The relationship between organizational configurations and performance has been a frequent albeit controversial subject of research in the field of strategic management Many studies have failed to find a link between configurations and performance leading prominent researchers to question the value of the concept of organizational configurations. Before the concept can be discarded, however, other plausible explanations for the lack of findings should be examined This paper examines the possible role of statistical power. Specifically, it may be that the sample sizes in many studies are too small to detect relationships between configurations and performance when such links are in fact, present Analysis of 24 tests of the configurations- performance link revealed that only 8 percent had samples large enough to detect all important relationships. Thus, there is reason to suspect that insufficient statistical power may help to explain extant results. Given these findings, suggestions are presented for improving the ability of configurational studies to detect relationships. [ABSTRACT FROM AUTHOR]

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next‐generation sequencing with a targeted 47‐gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors. The analyzed population included: 16,999 unmatched primary tumor and/or metastasis samples: 8,178 nonsmall cell lung cancers (5,098 primaries; 2,787 systemic metastases; 293 brain metastases), 7,064 breast cancers (3,496 primaries; 3,469 systemic metastases; 99 brain metastases) and 1,757 melanomas (660 primaries; 996 systemic metastases; 101 brain metastases). TOP2A expression was increased in brain metastases from all 3 cancers, and brain metastases overexpressed multiple proteins clustering around functions critical to DNA synthesis and repair and implicated in chemotherapy resistance, including RRM1, TS, ERCC1 and TOPO1. cMET was overexpressed in melanoma brain metastases relative to primary skin specimens. Brain metastasis patients may particularly benefit from therapeutic targeting of enzymes associated with DNA synthesis, replication and/or repair. What's new? Brain metastases are difficult to treat and generally lethal. Here, the authors sought clues to possible treatment targets by comparing the molecular characteristics of lung, breast, and skin cancers with those of brain metastases. They analyzed DNA sequence, protein expression, and gene amplification on over 17,000 samples, the largest metastases cohort ever studied. They found that the enzyme TOP2A, involved in DNA transcription, was enriched in the metastatic cells relative to the primary tumor cells. Other enzymes, involved in DNA synthesis, repair, and replication were also overexpressed in metastases, and could potentially be useful therapeutic targets. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Studies show that white men have a higher prevalence of Type 2 diabetes mellitus than women at a given age and BMI, but equivalent standardized data for other ethnic groups in the UK are sparse. Methods: This cross‐sectional study analysed UK Biobank data from 489 079 participants to compare the prevalence of diabetes mellitus across four major ethnic groups including: 471 700 (96.4%) white, 7871 (1.6%) South Asian, 7974 (1.6%) black and 1534 (0.3%) Chinese participants, before and after standardizing for age, socio‐economic status (SES), BMI and lifestyle factors including physical activity, TV viewing, fruit and vegetable intake, processed meat, red meat, oily fish, alcohol intake and smoking. A subgroup analysis of South Asians was also undertaken. Results: Crude diabetes prevalence was higher in men across all four ethnicities. After standardizing for age, SES, BMI and lifestyle factors, a significant sex difference in diabetes prevalence persisted in white (men 6.0% vs. women 3.6%), South Asian (21.0% vs. 13.8%) and black individuals (13.3% vs. 9.7%) (P < 0.0001); there was a non‐significant difference between Chinese men and women (7.1% vs. 5.5%) (P = 0.211). Sex differences persisted across South Asian subgroups. Conclusions: Men across a range of major ethnic groups including white, South Asian and black, have a higher prevalence of diabetes compared with women of similar age, BMI, SES and lifestyle in the UK. [ABSTRACT FROM AUTHOR]

During the past few years, research focused on individuals who identify as gay, lesbian, bisexual, and transgender (LGBT) have increased. However, much of this literature focuses on White LGBT individuals, and less on individuals who have intersected identities, such as being both gay/lesbian and a person of color. Consequently, this population becomes obscured in scholarly discourses, thus being made 'invisible' with regard to theory, research, and clinical interventions, with the result that clinicians are provided little or no knowledge of theories or best practices when working with individuals who are both sexual minority and people of color. This article discusses an integrated theoretical and treatment process when working with clients who are navigating multiple oppressed identities. [ABSTRACT FROM AUTHOR]

Background Atrial fibrillation (AF) is often treated with catheter ablation, which induces scar formation to isolate misfiring electrical signals in the left atrium. Successful ablation restores sinus rhythm at the cost of replacing viable myocardium with scar. The impact of ablation scar on mechanical function of the left atrium is poorly understood. Objective We used a computational model to simulate various ablation patterns and determine their effect on atrial global and regional mechanical function. Methods A coupled finite-element and hemodynamic circuit model of the left atrium that represents the regional and global mechanics in paroxysmal AF patients was modified to simulate different ablation patterns: step-wise pulmonary vein isolation (PVI), wide area circumferential ablation (WACA), and a posterior ablation developed by nContact, Inc (Morrisville, NC, USA). Atrial pressure-volume relationships and regional wall motion were compared among the models. Results Ablation increased passive stiffness and decreased active work performed by the atrium. Active emptying volume decreased with increasing scar by up to 44% (11 mL) at a scar volume of 31%. At matched scar volumes, WACA decreased active emptying more severely than PVI and nContact. Similarly, wall motion was depressed most in the WACA model because WACA involved portions of the lateral wall with higher baseline motion. Conclusion Simulated ablation depressed atrial mechanical function to an extent that depended on both scar volume and location, primarily through reducing active emptying. Placing ablation scar in regions with high baseline motion resulted in greater depression of active function, while ablation of the posterior wall was less disruptive. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the safety and therapeutic efficacy of percutaneous microwave ablation (MWA) for colorectal pulmonary metastases.Methods: Retrospective review of CT-guided lung MWA at a single tertiary institution. Adverse events within 30 days of MWA were considered procedure-related complications. Imaging follow-up was with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT and contrast-enhanced CT. Response of index tumours was assessed using modified response evaluation criteria in solid tumours (mRECIST).Results: The CT-guided lung MWA was performed in 14 patients with treatment of 20 colorectal pulmonary metastases during 19 procedures. Mean follow-up from completion of the treatment protocol was 24.4 ± 11.8 months. Primary and secondary technique effectiveness rates were 75% and 50% respectively. Mean pre- and post-procedural carcino-embryonic antigen (CEA) levels were 7.9 ± 10.8 µg/L and 2.5 ± 2.1 µg/L respectively. Procedure-related complications were major in three procedures (15.8%) and minor in six procedures (31.6%). No procedure-related deaths occurred.Conclusion: Microwave ablation is safe and efficacious in the local control of colorectal pulmonary metastases. The frequent systemic disease progression despite local control would favour a minimally invasive treatment option over invasive surgery in the setting of oligometastatic disease. [ABSTRACT FROM AUTHOR]

Catheter Ablation of Arrhythmia During Pregnancy Cardiac arrhythmia as a complication of pregnancy can be problematic to maternal health and fetal life and development. Catheter ablation of tachyarrhythmias during pregnancy has been successfully performed in selected patients with limited experience. Techniques to limit maternal and fetal radiation exposure, including intracardiac echo and electroanatomic mapping systems, are particularly important in this setting. Specific accommodations are necessary in the care of the gravid patient during catheter ablation. [ABSTRACT FROM AUTHOR]

Major Complications Following EP Procedures Background Despite growing attention to performance and quality measures, national standards for reporting of outcomes after all electrophysiology (EP) procedures have not yet been developed. We sought to characterize the incidence and timing of adverse events up to 30 days after EP procedures at a tertiary academic medical center. Methods and Results We prospectively followed all patients undergoing EP procedures between January 2010 and September 2012. All were followed for 30 days postprocedure either in clinic or by telephone. Major complications were defined as events related to the procedure that led to prolongation of hospital stay or readmission, required additional procedural intervention, or resulted in death or significant injury. These were further categorized as intraprocedure, postprocedure, or postdischarge events. Seven EP physicians collectively adjudicated whether complications were directly related to the procedure. A total of 3,213 procedures were performed. Major complications occurred in 2.2% of patients; 49% of these events occurred after discharge. Death occurred in 0.6% of patients; 73% of these deaths were found to be secondary to worsening of the patient's underlying comorbid conditions and unrelated to the procedure. Conclusions When considering national standards for reporting outcomes of all EP procedures, continued follow-up after discharge is important. In our cohort, half of major complications occurring within 30 days occurred after discharge. In addition, three-quarters of deaths within 30 days were not directly related to the procedure and caution should be used in using all-cause mortality as an outcome measure for EP procedures. [ABSTRACT FROM AUTHOR]

Screening of protein variants requires specific detection methods to assay protein levels and stability in crude mixtures. Many strategies apply fluorescence-detection size-exclusion chromatography (FSEC) using green fluorescent protein (GFP) fusion proteins to qualitatively monitor expression, stability, and monodispersity. However, GFP fusion proteins have several important disadvantages; including false-positives, protein aggregation after proteolytic removal of GFP, and reductions in protein yields without the GFP fusion. Here we describe a FSEC screening strategy based on a fluorescent multivalent NTA probe that interacts with polyhistidine-tags on target proteins. This method overcomes the limitations of GFP fusion proteins, and can be used to rank protein production based on qualitative and quantitative parameters. Domain boundaries of the human G-protein coupled adenosine A2a receptor were readily identified from crude detergent-extracts of a library of construct variants transiently produced in suspension-adapted HEK293-6E cells. Well expressing clones of MraY, an important bacterial infection target, could be identified from a library of 24 orthologs. This probe provides a highly sensitive tool to detect target proteins to expression levels down to 0.02 mg/L in crude lysate, and requires minimal amounts of cell culture. [ABSTRACT FROM AUTHOR]

Dairy cow bone phosphorus (P) mobilization and deposition and their influence on P requirements were studied over the lactation cycle. Thirty Holsteins received a common diet during the dry period and one of the following three dietary treatments that varied in P percentage during the subsequent lactation (44 weeks): (i) 0.36 throughout (constant P, 0.36-0.36-0.36), (ii) 0.36 for 30 weeks then 0.29 for 14 weeks (P changed once, 0.36-0.36-0.29), and (iii) 0.43 for 10 weeks, 0.36 for 20 weeks, and 0.29 for 14 weeks (P changed twice, 0.43-0.36-0.29). Six P balance studies were conducted during the experiment, including one during the dry period and five along lactation, based on P intake, faecal P, urinary P and milk P, when appropriate. Blood samples were taken during balance to analyse bone formation (osteocalcin) and resorption (pyridinoline) marker concentrations and rib biopsies performed to determine bone P content. Phosphorus balance was negative during weeks −4 to −1 relative to lactation for all groups and remained negative for cows fed 0.36% P during weeks 1-5, but showed a positive value for cows that received 0.43% P. The balance was close to zero for all groups at weeks 19-23 and showed a clear retention during weeks 38-42; by the end of lactation, cows re-stored most of the P mobilized earlier. The pattern in P balance was consistent with changes in blood bone metabolism marker concentrations, rib bone P content, and faecal and urinary P concentrations over the experiment, indicating that cows, irrespective of the dietary P treatments received, mobilized P from bone during the late dry period when fed a low-Ca diet and early lactation, and re-stored P in late lactation. This dynamic of P metabolism can have important implications for dietary P requirements and ration formulations. [ABSTRACT FROM AUTHOR]

Cardiovascular disease remains a major source of morbidity and mortality in type 2 diabetes mellitus. This article examines the recent evidence from trials and related meta-analyses on the effects of glycaemic control on cardiovascular disease (and, to a lesser extent, microvascular outcomes) in diabetes, and compares this with evidence accrued from blood pressure and statin trials. On the basis of such evidence, as well as pragmatic considerations, it is clear that clinicians should place stronger emphasis on lipid and blood pressure management to lessen cardiovascular risks. At the same time, cardiovascular disease benefits of glycaemia reduction appear less pronounced, with patient characteristics critically influencing risk to benefit ratio. Recent guidelines now reflect recent observations on glycaemic control (with relaxed targets in specific patient groups), whereas future guidelines should encourage physicians to prioritize lipid-lowering and blood pressure management in patients with diabetes. [ABSTRACT FROM AUTHOR]