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The B-lymphocyte accessory molecule Ig-alpha (Ig-α) is encoded by the mouse B cell-specific gene (mb-1), and along with the Ig-beta (Ig-β) molecule and a membrane bound immunoglobulin (mIg) makes up the B-cell receptor (BCR). Ig-α and Ig-β form a heterodimer structure that upon antigen binding and receptor clustering primarily initiates and controls BCR intracellular signaling via a phosphorylation cascade, ultimately triggering an effector response. The signaling capacity of Ig-α is contained within its immunoreceptor tyrosine-based activation motif (ITAM), which is also a key component for intracellular signaling initiation in other immune cell-specific receptors. Although numerous studies have been devoted to the mb-1 gene product, Ig-α, and its signaling mechanism, an evolutionary analysis of the mb-1 gene has been lacking until now. In this study, mb-1 coding sequences from 19 species were compared using Bayesian inference. Analysis revealed a gene phylogeny consistent with an expected species divergence pattern, clustering species from the primate order separate from lower mammals and other species. In addition, an overall comparison of non-synonymous and synonymous nucleotide mutational changes suggests that the mb-1 gene has undergone purifying selection throughout its evolution.

Background: Heart failure (HF) patients often depend on driving for access to specialty care. We analyzed a public-use copy of the Cardiovascular Health Study (CHS) data to determine if HF is a risk factor for driving cessation and to identify other risk factors for driving cessation among those with HF., Methods and Results: Of the 5,383 community-dwelling drivers aged ≥65 years (mean age 73 years, 55% women, 13% African American), 839 had HF: 246 had baseline prevalent HF and 593 developed incident HF before driving cessation during 9 years of follow-up. Incident driving cessation occurred at rates of 3,980 and 3,709 per 10,000 person-years of follow-up for those with and without HF, respectively (unadjusted hazard ratio [HR] associated with HF as a time-varying variable: 2.13, 95% confidence interval [CI] 1.83-2.47; P < .001). This association remained unchanged after multivariable risk adjustment (HR 1.43, 95% CI 1.21-1.68; P < .001). Among the 839 older drivers with HF, independent predictors for incident driving cessation were age ≥75 years (HR 1.99, 95% CI 1.44-2.73; P < .001), female gender (HR 1.93, 95% CI 1.37-2.74; P < .001), difficulty walking half a mile (HR 1.47 (1.04-2.08); P = .028), vision problems (HR 1.47, 95% CI 1.07-2.02; P = .018), and stroke as a time-varying covariate (HR 1.96, 95% CI 1.38-2.79; P < .001)., Conclusions: HF is an independent risk factor for incident driving cessation among community-dwelling older drivers. Several patient characteristics predicted driving cessation in older HF patients, which may be targets for interventions to prevent driving cessation among these patients., (Published by Elsevier Inc.)

Background and Purpose: Accurate conformal radiotherapy treatment requires manual delineation of target volumes and organs at risk (OAR) that is both time-consuming and subject to large inter-user variability. One solution is atlas-based automatic segmentation (ABAS) where a priori information is used to delineate various organs of interest. The aim of the present study is to establish the accuracy of one such tool for the head and neck (H&N) using two different evaluation methods., Materials and Methods: Two radiotherapy centres were provided with an ABAS tool that was used to outline the brainstem, parotids and mandible on several patients. The results were compared to manual delineations for the first centre (EM1) and reviewed/edited for the second centre (EM2), both of which were deemed as equally valid gold standards. The contours were compared in terms of their volume, sensitivity and specificity with the results being interpreted using the Dice similarity coefficient and a receiver operator characteristic (ROC) curve., Results: Automatic segmentation took typically approximately 7min for each patient on a standard PC. The results indicated that the atlas contour volume was generally within +/-1SD of each gold standard apart from the parotids for EM1 and brainstem for EM2 that were over- and under-estimated, respectively (within +/-2SD). The similarity of the atlas contours with their respective gold standard was satisfactory with an average Dice coefficient for all OAR of 0.68+/-0.25 for EM1 and 0.82+/-0.13 for EM2. All data had satisfactory sensitivity and specificity resulting in a favourable position in ROC space., Conclusions: These tests have shown that the ABAS tool exhibits satisfactory sensitivity and specificity for the OAR investigated. There is, however, a systematic over-segmentation of the parotids (EM1) and under-segmentation of the brainstem (EM2) that require careful review and editing in the majority of cases. Such issues have been discussed with the software manufacturer and a revised version is due for release.

Background: Stopping driving has significant negative consequences for older adults, but there is no simple, reliable screening tool to predict driving cessation. We sought to determine if self-rated health (SRH) was an independent predictor of driving cessation among older adults., Methods: Data on SRH (poor, fair, good, very good, or excellent), medical diagnoses, physical performance, visual acuity, driving status, and other relevant covariates were collected from 649 community-dwelling older Alabama drivers during in-home interviews. Using multivariable logistic regression analyses, we estimated the association of SRH with driving cessation 2 years later., Results: Participants had a mean age of 74 years; 43% were women, 41% African American, and 48% rural. Overall, 36% reported poor to fair SRH at baseline, and 11% had stopped driving after 2 years. Compared to 8% of drivers with good to excellent SRH, 17% with poor to fair health stopped driving (adjusted odds ratio [OR], 1.93; 95% confidence interval [CI], 1.09-3.41; p=.025). Lower Short Physical Performance Battery (SPPB) scores (adjusted OR, 0.86; 95% CI, 0.78-0.95; p=.001) and older age (adjusted OR, 1.06 per year; 95% CI, 1.01-1.11; p=.010) were also associated with driving cessation. Receiver operating characteristics curves documented similar predictive discrimination (c statistics) for SRH (0.72), the SPPB (0.70), and a count of comorbidities based on the Charlson Comorbidity Index (0.73)., Conclusions: Poor to fair SRH predicted incident driving cessation after 2 years in a cohort of older adults. SRH can be easily obtained during clinic visits to identify at-risk drivers.

Background: The appropriate roles for generalists and cardiologists in the care of patients with heart failure (HF) are unknown. The objective of this retrospective cohort study was to determine whether consultation between generalists and cardiologists was associated with better quality and outcomes of HF care., Methods: We studied left ventricular function evaluation (LVFE) and angiotensin-converting enzyme inhibitor (ACEI) use and 90-day readmission and 90-day mortality rates in patients with HF who were hospitalized. Patient care was categorized into cardiologist (solo), generalist (solo), or consultative cares. The processes and outcomes of care were compared by care category using logistic regression analyses fit with generalized linear mixed models to adjust for hospital-related clustering., Results: Of the 1075 patients studied, 13% received cardiologist care, 55% received generalist care, and 32% received consultative care. More patients who received consultative care (75%) received LVFE than patients who received generalist care (36%) and cardiologist care (53%; P <.001). Fewer patients who received solo care (54% each) received ACEI compared with 71% of patients who received consultative care (P <.001). After multivariable adjustment, consultative care was associated with higher odds of LVFE than generalist care (adjusted odds ratio [OR], 6.06; 95% CI, 3.97-9.26) or cardiologist care (adjusted OR, 2.96; 95% CI, 1.70-5.13) care. Consultation was also associated with higher odds of ACEI use compared with generalist (adjusted OR, 2.42; 95% CI, 1.42-4.12) or cardiologist (adjusted OR, 2.32; 95% CI, 1.14-4.72) care. Compared with patients who received generalist care, patients who received consultative care had lower odds of 90-day readmission (adjusted OR, 0.54; 95% CI, 0.34-0.86)., Conclusion: Collaboration between generalists and cardiologists, rather than solo care by either, was associated with better HF processes and outcomes of care.