Chronic psychosocial and financial burden accelerates 5-year telomere shortening: findings from the Coronary Artery Risk Development in Young Adults Study.

Leukocyte telomere length, a marker of immune system function, is sensitive to exposures such as psychosocial stressors and health-maintaining behaviors. Past research has determined that stress experienced in adulthood is associated with shorter telomere length, but is limited to mostly cross-sectional reports. We test whether repeated reports of chronic psychosocial and financial burden is associated with telomere length change over a 5-year period (years 15 and 20) from 969 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a longitudinal, population-based cohort, ages 18-30 at time of recruitment in 1985. We further examine whether multisystem resiliency, comprised of social connections, health-maintaining behaviors, and psychological resources, mitigates the effects of repeated burden on telomere attrition over 5 years. Our results indicate that adults with high chronic burden do not show decreased telomere length over the 5-year period. However, these effects do vary by level of resiliency, as regression results revealed a significant interaction between chronic burden and multisystem resiliency. For individuals with high repeated chronic burden and low multisystem resiliency (1 SD below the mean), there was a significant 5-year shortening in telomere length, whereas no significant relationships between chronic burden and attrition were evident for those at moderate and higher levels of resiliency. These effects apply similarly across the three components of resiliency. Results imply that interventions should focus on establishing strong social connections, psychological resources, and health-maintaining behaviors when attempting to ameliorate stress-related decline in telomere length among at-risk individuals

Predicting the location of the hip joint centres, impact of age group and sex

Clinical gait analysis incorporating three-dimensional motion analysis plays a key role in planning surgical treatments in people with gait disability. The position of the Hip Joint Centre (HJC) within the pelvis is thus critical to ensure accurate data interpretation. The position of the HJC is determined from regression equations based on anthropometric measurements derived from relatively small datasets. Current equations do not take sex or age into account, even though pelvis shape is known to differ between sex, and gait analysis is performed in populations with wide range of age. Three dimensional images of 157 deceased individuals (37 children, 120 skeletally matured) were collected with computed tomography. The location of the HJC within the pelvis was determined and regression equations to locate the HJC were developed using various anthropometrics predictors. We determined if accuracy improved when age and sex were introduced as variables. Statistical analysis did not support differentiating the equations according to sex. We found that age only modestly improved accuracy. We propose a range of new regression equations, derived from the largest dataset collected for this purpose to date

Impact of High Mathematics Education on the Number Sense

In adult number processing two mechanisms are commonly used: approximate estimation of quantity and exact calculation. While the former relies on the approximate number sense (ANS) which we share with animals and preverbal infants, the latter has been proposed to rely on an exact number system (ENS) which develops later in life following the acquisition of symbolic number knowledge. The current study investigated the influence of high level math education on the ANS and the ENS. Our results showed that the precision of non-symbolic quantity representation was not significantly altered by high level math education. However, performance in a symbolic number comparison task as well as the ability to map accurately between symbolic and non-symbolic quantities was significantly better the higher mathematics achievement. Our findings suggest that high level math education in adults shows little influence on their ANS, but it seems to be associated with a better anchored ENS and better mapping abilities between ENS and ANS

Electrical characterization and nanoscale surface morphology of optimized Ti/Al/Ta/Au ohmic contact for AlGaN/GaN HEMT

Good ohmic contacts with low contact resistance, smooth surface morphology, and a well-defined edge profile are essential to ensure optimal device performances for the AlGaN/GaN high electron mobility transistors [HEMTs]. A tantalum [Ta] metal layer and an SiNx thin film were used for the first time as an effective diffusion barrier and encapsulation layer in the standard Ti/Al/metal/Au ohmic metallization scheme in order to obtain high quality ohmic contacts with a focus on the thickness of Ta and SiNx. It is found that the Ta thickness is the dominant factor affecting the contact resistance, while the SiNx thickness affects the surface morphology significantly. An optimized Ti/Al/Ta/Au ohmic contact including a 40-nm thick Ta barrier layer and a 50-nm thick SiNx encapsulation layer is preferred when compared with the other conventional ohmic contact stacks as it produces a low contact resistance of around 7.27 × 10-7 Ω·cm2 and an ultra-low nanoscale surface morphology with a root mean square deviation of around 10 nm. Results from the proposed study play an important role in obtaining excellent ohmic contact formation in the fabrication of AlGaN/GaN HEMTs

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GRNesCre), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress

System Dynamics to Model the Unintended Consequences of Denying Payment for Venous Thromboembolism after Total Knee Arthroplasty

Background: The Hospital Acquired Condition Strategy (HACS) denies payment for venous thromboembolism (VTE) after total knee arthroplasty (TKA). The intention is to reduce complications and associated costs, while improving the quality of care by mandating VTE prophylaxis. We applied a system dynamics model to estimate the impact of HACS on VTE rates, and potential unintended consequences such as increased rates of bleeding and infection and decreased access for patients who might benefit from TKA. Methods and Findings: The system dynamics model uses a series of patient stocks including the number needing TKA, deemed ineligible, receiving TKA, and harmed due to surgical complication. The flow of patients between stocks is determined by a series of causal elements such as rates of exclusion, surgery and complications. The number of patients harmed due to VTE, bleeding or exclusion were modeled by year by comparing patient stocks that results in scenarios with and without HACS. The percentage of TKA patients experiencing VTE decreased approximately 3-fold with HACS. This decrease in VTE was offset by an increased rate of bleeding and infection. Moreover, results from the model suggest HACS could exclude 1.5% or half a million patients who might benefit from knee replacement through 2020. Conclusion: System dynamics modeling indicates HACS will have the intended consequence of reducing VTE rates. However, an unintended consequence of the policy might be increased potential harm resulting from over administration of prophylaxis, as well as exclusion of a large population of patients who might benefit from TKA