Neighborhood disadvantage across the transition from adolescence to adulthood and risk of metabolic syndrome

This study investigates the association between neighborhood disadvantage from adolescence to young adulthood and metabolic syndrome using a life course epidemiology framework. Data from the United States-based National Longitudinal Study of Adolescent to Adult Health (n = 9500)and a structural equation modeling approach were used to test neighborhood disadvantage across adolescence, emerging adulthood, and young adulthood in relation to metabolic syndrome. Adolescent neighborhood disadvantage was directly associated with metabolic syndrome in young adulthood. Evidence supporting an indirect association between adolescent neighborhood disadvantage and adult metabolic syndrome was not supported. Efforts to improve cardiometabolic health may benefit from strategies earlier in life

Predicting function from sequence in a large multifunctional toxin family

Venoms contain active substances with highly specific physiological effects and are increasingly being used as sources of novel diagnostic, research and treatment tools for human disease. Experimental characterisation of individual toxin activities is a severe rate-limiting step in the discovery process, and in-silico tools which allow function to be predicted from sequence information are essential. Toxins are typically members of large multifunctional families of structurally similar proteins that can have different biological activities, and minor sequence divergence can have significant consequences. Thus, existing predictive tools tend to have low accuracy. We investigated a classification model based on physico-chemical attributes that can easily be calculated from amino-acid sequences, using over 250 (mostly novel) viperid phospholipase A2 toxins. We also clustered proteins by sequence profiles, and carried out in-vitro tests for four major activities on a selection of isolated novel toxins, or crude venoms known to contain them. The majority of detected activities were consistent with predictions, in contrast to poor performance of a number of tested existing predictive methods. Our results provide a framework for comparison of active sites among different functional sub-groups of toxins that will allow a more targeted approach for identification of potential drug leads in the future

Adiabatic following criterion, estimation of the nonadiabatic excitation fraction and quantum jumps

An accurate theory describing adiabatic following of the dark, nonabsorbing state in the three-level system is developed. An analytical solution for the wave function of the particle experiencing Raman excitation is found as an expansion in terms of the time varying nonadiabatic perturbation parameter. The solution can be presented as a sum of adiabatic and nonadiabatic parts. Both are estimated quantitatively. It is shown that the limiting value to which the amplitude of the nonadiabatic part tends is equal to the Fourier component of the nonadiabatic perturbation parameter taken at the Rabi frequency of the Raman excitation. The time scale of the variation of both parts is found. While the adiabatic part of the solution varies slowly and follows the change of the nonadiabatic perturbation parameter, the nonadiabatic part appears almost instantly, revealing a jumpwise transition between the dark and bright states. This jump happens when the nonadiabatic perturbation parameter takes its maximum value.Comment: 33 pages, 8 figures, submitted to PRA on 28 Oct. 200

Patella malalignment, pain and patellofemoral progression: the Health ABC Study

SummaryObjectivePatellofemoral (PF) joint osteoarthritis (OA) is strongly correlated with lower extremity disability and knee pain. Risk factors for pain and structural progression in PF OA are poorly understood. Our objective was to determine the association between patella malalignment and its relation to pain severity, and PF OA disease progression.MethodsWe conducted an analysis of data from the Health ABC knee OA study. Health ABC is a community based, multi-center cohort study of 3075 Caucasian and Black men and women aged 70–79 at enrollment. Weight bearing skyline knee X-rays were obtained in a subset (595) of subjects, with and without knee pain, at year 2 and year 5 (mean follow-up 36 months). Films were read paired, and PF osteophytes (OST) and joint space narrowing (JSN) were scored on a 0–3 scale using the Osteoarthritis Research Society International atlas. We defined progression of PF OA as any increase in JSN score. Three measures of patella malalignment were made: sulcus angle; patella tilt angle; and patella subluxation medially or laterally (bisect offset). Knee symptoms were assessed using a knee specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain subscale. We assessed the relationship between baseline patella malalignment and pain severity (linear regression for WOMAC) and compartment specific PF OA progression (logistic regression for dichotomous outcomes). We classified continuous measures of patella alignment into quartile groups. We performed multivariable adjusted logistic regression models, including age, gender and body mass index (BMI) to assess the relation of baseline patella alignment to the occurrence of PF JSN progression using generalized estimating equations (GEE).ResultsThe subjects had a mean age 73.6 (SD 2.9), BMI 28.8 (SD 4.9), 40.3% male, and 46% were Black. Medial displacement of the patella predisposed to medial JSN progression; odds for each quartile 1, 1.2, 1.2, 2.2 (P for trend=0.03), whilst protecting from lateral JSN progression; odds for each quartile 1, 0.7, 0.6, 0.4 (P for trend=0.0004). Increasing patella tilt protected from medial JSN progression; odds for each quartile 1, 0.8, 0.5, 0.2 (P<0.0001) and trended to increasing pain severity (P=0.09).ConclusionPatella malalignment is associated with PF disease progression. Medial displacement and tilt of the patella predisposes to medial JSN progression, whilst lateral displacement is predictive of lateral JSN progression. The influence of patella malalignment has important implications since it is potentially modifiable through footwear, taping and/or knee bracing

B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage

B-1a cells are long-lived, self-renewing innate-like B cells that predominantly inhabit the peritoneal and pleural cavities. In contrast to conventional B-2 cells, B-1a cells have a receptor repertoire that is biased towards bacterial and self-antigens, promoting a rapid response to infection and clearing of apoptotic cells. Although B-1a cells are known to primarily originate from fetal tissues, the mechanisms by which they arise has been a topic of debate for many years. Here we show that in the fetal liver versus bone marrow environment, reduced IL-7R/STAT5 levels promote immunoglobulin kappa gene recombination at the early pro-B cell stage. As a result, differentiating B cells can directly generate a mature B cell receptor (BCR) and bypass the requirement for a pre-BCR and pairing with surrogate light chain. This 'alternate pathway' of development enables the production of B cells with self-reactive, skewed specificity receptors that are peculiar to the B-1a compartment. Together our findings connect seemingly opposing lineage and selection models of B-1a cell development and explain how these cells acquire their unique properties

Empirical Evidence on the Use of Credit Scoring for Predicting Insurance Losses with Psycho-social and Biochemical Explanations

An important development in personal lines of insurance in the United States is the use of credit history data for insurance risk classification to predict losses. This research presents the results of collaboration with industry conducted by a university at the request of its state legislature. The purpose was to see the viability and validity of the use of credit scoring to predict insurance losses given its controversial nature and criticism as redundant of other predictive variables currently used. Working with industry and government, this study analyzed more than 175,000 policyholders’ information for the relationship between credit score and claims. Credit scores were significantly related to incurred losses, evidencing both statistical and practical significance. We investigate whether the revealed relationship between credit score and incurred losses was explainable by overlap with existing underwriting variables or whether the credit score adds new information about losses not contained in existing underwriting variables. The results show that credit scores contain significant information not already incorporated into other traditional rating variables (e.g., age, sex, driving history). We discuss how sensation seeking and self-control theory provide a partial explanation of why credit scoring works (the psycho-social perspective). This article also presents an overview of biological and chemical correlates of risk taking that helps explain why knowing risk-taking behavior in one realm (e.g., risky financial behavior and poor credit history) transits to predicting risk-taking behavior in other realms (e.g., automobile insurance incurred losses). Additional research is needed to advance new nontraditional loss prediction variables from social media consumer information to using information provided by technological advances. The evolving and dynamic nature of the insurance marketplace makes it imperative that professionals continue to evolve predictive variables and for academics to assist with understanding the whys of the relationships through theory development.IC2 Institut

Comparative study of density functional theories of the exchange-correlation hole and energy in silicon

We present a detailed study of the exchange-correlation hole and exchange-correlation energy per particle in the Si crystal as calculated by the Variational Monte Carlo method and predicted by various density functional models. Nonlocal density averaging methods prove to be successful in correcting severe errors in the local density approximation (LDA) at low densities where the density changes dramatically over the correlation length of the LDA hole, but fail to provide systematic improvements at higher densities where the effects of density inhomogeneity are more subtle. Exchange and correlation considered separately show a sensitivity to the nonlocal semiconductor crystal environment, particularly within the Si bond, which is not predicted by the nonlocal approaches based on density averaging. The exchange hole is well described by a bonding orbital picture, while the correlation hole has a significant component due to the polarization of the nearby bonds, which partially screens out the anisotropy in the exchange hole.Comment: 16 pages, 5 figures, RevTeX, added conten

Decay of the metastable phase in d=1 and d=2 Ising models

We calculate perturbatively the tunneling decay rate $\Gamma$ of the metastable phase in the quantum d=1 Ising model in a skew magnetic field near the coexistence line $0<h_{x}<1, h_{z}\to -0$ at T=0. It is shown that $\Gamma$ oscillates in the magnetic field $h_{z}$ due to discreteness of the excitation energy spectrum. After mapping of the obtained results onto the extreme anisotropic d=2 Ising model at $T<T_c$, we verify in the latter model the droplet theory predictions for the free energy analytically continued to the metastable phase. We find also evidence for the discrete-lattice corrections in this metastable phase free energy.Comment: 4 pages, REVTe