The Role of Underutilization of Protective Behavioral Strategies in the Relation of Social Anxiety with Risky Drinking

Social anxiety is prominent among undergraduates and increases the risk of experiencing alcohol problems. In fact, social anxiety more than quadruples the risk of developing an alcohol use disorder, yet it is inconsistently related to heavier drinking. Inconsistent findings may be due to lack of attention on protective behavioral strategies (PBS) among socially anxious drinkers. PBS are cognitive-behavioral strategies to reduce drinking and alcohol-related harm. Due to the nature of social anxiety, affected individuals may be especially vulnerable to PBS underutilization, leading to heavier and more problematic drinking. The current study examined the mediating role of PBS in the relationships of social anxiety with past-month drinking and alcohol problems using cross-sectional data among current (past-month) heavy undergraduate drinkers (N = 431). Social anxiety was significantly positively related to past-month alcohol problems and peak drinking. Social anxiety was significantly negatively related to typical drinking, drinking frequency, and PBSS Manner of Drinking. Social anxiety was indirectly (via PBSS Manner of Drinking) related to greater past-month peak drinks and more drinking problems. Findings suggest that socially anxious persons may be vulnerable to heavier and more problematic drinking due to PBS underutilization. Treatment implications are discussed

The trans-activation domain of the sporulation response regulator Spo0A revealed by X-ray crystallography

Sporulation in Bacillus involves the induction of scores of genes in a temporally and spatially co-ordinated programme of cell development. Its initiation is under the control of an expanded two-component signal transduction system termed a phosphorelay. The master control element in the decision to sporulate is the response regulator, Spo0A, which comprises a receiver or phosphoacceptor domain and an effector or transcription activation domain. The receiver domain of Spo0A shares sequence similarity with numerous response regulators, and its structure has been determined in phosphorylated and unphosphorylated forms. However, the effector domain (C-Spo0A) has no detectable sequence similarity to any other protein, and this lack of structural information is an obstacle to understanding how DNA binding and transcription activation are controlled by phosphorylation in Spo0A. Here, we report the crystal structure of C-Spo0A from Bacillus stearothermophilus revealing a single alpha -helical domain comprising six alpha -helices in an unprecedented fold. The structure contains a helix-turn-helix as part of a three alpha -helical bundle reminiscent of the catabolite gene activator protein (CAP), suggesting a mechanism for DNA binding. The residues implicated in forming the sigma (A)-activating region clearly cluster in a flexible segment of the polypeptide on the opposite side of the structure from that predicted to interact with DNA. The structural results are discussed in the context of the rich array of existing mutational data

Fluctuation Dominated Josephson Tunneling with a Scanning Tunneling Microscope

We demonstrate Josephson tunneling in vacuum tunnel junctions formed between a superconducting scanning tunneling microscope tip and a Pb film, for junction resistances in the range 50-300 k$\Omega$. We show that the superconducting phase dynamics is dominated by thermal fluctuations, and that the Josephson current appears as a peak centered at small finite voltages. In the presence of microwave fields (f=15.0 GHz) the peak decreases in magnitude and shifts to higher voltages with increasing rf power, in agreement with theory.Comment: 4 pages, REVTeX, submitted to PR

Further explorations of illness uncertainty: Carer’s experiences of Parkinson’s disease

Objective: Dominant models of illness uncertainty define uncertainty as ‘an inability to determine the meaning of illness-related events’. Recent research has shown patient uncertainty to be multidimensional encompassing personal issues indirectly affected by illness. The nature of carer uncertainty has yet to be fully explored. The present study aimed to investigate the nature of illness uncertainty in the carers of patients with Parkinson’s disease (PD). Design: Eighteen carers of a spouse with PD participated in semi-structured interviews. Transcripts were thematically analysed, statements were coded as uncertain if they reflected ‘a lack of certainty, or a state of limited knowledge, understanding or worry regarding an existing or future outcome’. Results: The domains of uncertainty expressed by carers closely fitted the five domain framework of patient uncertainty: symptoms and prognosis, medical management, self-management, social functioning and impact. An additional ‘carer-role’ domain was identified. Conclusions: Carer uncertainty about PD went beyond issues directly related to the illness. The findings have implications for research into uncertainty suggesting that widely used measures may not be accurately capturing the nature of carer uncertainty about chronic illness. The breadth of uncertainty reported has implications for the provision of appropriate support to improve caregiver well-being

Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study

OBJECTIVE: The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. METHODS: The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. RESULTS: Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). CONCLUSION: The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA

The Politics of Commerce : The Congress of Chambers of Commerce of the Empire, 1886-1914

Peer reviewedPublisher PD

NCCTG Study N9741: Leveraging Learning from an NCI Cooperative Group Phase III Trial

N9741 is a clinical trial in patients with metastatic colorectal cancer that was originally written in 1997 and completed patient accrual in 2004. One thousand seven hundred thirty-one patients were enrolled in the study. During the conduct of the trial, N9741 was repeatedly modified to adapt to toxicity findings, to add evaluation of oxaliplatin to what was originally a trial examining various schedules of irinotecan-based therapy, and to ask evolving questions. The trial led to a new U.S. Food and Drug Administration indication for 5-fluorouracil, leucovorin, and oxaliplatin as indicated for the treatment of previously untreated patients with metastatic colorectal cancer and helped to change the standard of care for the disease in the U.S. and worldwide. The data from the trial have been used to study multiple regimens, pharmacogenetics, and quality of life issues, to correlate plasma protein levels with outcomes, to inform trial methodology, and to perform economic analyses. To date nearly 30 papers and an even larger number of abstracts have been based upon data arising from the study. The history of the trial and the major findings are summarized in this review

Pulse Sequence Resilient Fast Brain Segmentation

Accurate automatic segmentation of brain anatomy from $T_1$-weighted~($T_1$-w) magnetic resonance images~(MRI) has been a computationally intensive bottleneck in neuroimaging pipelines, with state-of-the-art results obtained by unsupervised intensity modeling-based methods and multi-atlas registration and label fusion. With the advent of powerful supervised convolutional neural networks~(CNN)-based learning algorithms, it is now possible to produce a high quality brain segmentation within seconds. However, the very supervised nature of these methods makes it difficult to generalize them on data different from what they have been trained on. Modern neuroimaging studies are necessarily multi-center initiatives with a wide variety of acquisition protocols. Despite stringent protocol harmonization practices, it is not possible to standardize the whole gamut of MRI imaging parameters across scanners, field strengths, receive coils etc., that affect image contrast. In this paper we propose a CNN-based segmentation algorithm that, in addition to being highly accurate and fast, is also resilient to variation in the input $T_1$-w acquisition. Our approach relies on building approximate forward models of $T_1$-w pulse sequences that produce a typical test image. We use the forward models to augment the training data with test data specific training examples. These augmented data can be used to update and/or build a more robust segmentation model that is more attuned to the test data imaging properties. Our method generates highly accurate, state-of-the-art segmentation results~(overall Dice overlap=0.94), within seconds and is consistent across a wide-range of protocols.Comment: Accepted at MICCAI 201

Multidimensional heritability analysis of neuroanatomical shape

In the dawning era of large-scale biomedical data, multidimensional phenotype vectors will play an increasing role in examining the genetic underpinnings of brain features, behaviour and disease. For example, shape measurements derived from brain MRI scans are multidimensional geometric descriptions of brain structure and provide an alternate class of phenotypes that remains largely unexplored in genetic studies. Here we extend the concept of heritability to multidimensional traits, and present the first comprehensive analysis of the heritability of neuroanatomical shape measurements across an ensemble of brain structures based on genome-wide SNP and MRI data from 1,320 unrelated, young and healthy individuals. We replicate our findings in an extended twin sample from the Human Connectome Project (HCP). Our results demonstrate that neuroanatomical shape can be significantly heritable, above and beyond volume, and can serve as a complementary phenotype to study the genetic determinants and clinical relevance of brain structure.National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41EB015896)United States. National Institutes of Health (S10RR023043)United States. National Institutes of Health (S10RR023401)United States. National Institutes of Health (K25CA181632)United States. National Institutes of Health (K01MH099232)United States. National Institutes of Health (K99MH101367)United States. National Institutes of Health (R21AG050122-01A1)United States. National Institutes of Health (R41AG052246-01)United States. National Institutes of Health (1K25EB013649-01)United States. National Institutes of Health (K24MH094614)United States. National Institutes of Health (R01MH101486