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Predicting suicides after outpatient mental health visits in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).
The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines (VA/DoD CPG) require comprehensive suicide risk assessments for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessments. Given that clinician-based assessments are not known to be strong predictors of suicide, we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among outpatients. We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides. Four machine learning classifiers (naive Bayes, random forests, support vector regression and elastic net penalized regression) were explored. Of the Army suicides in 2004-2009, 41.5% occurred among 12.0% of soldiers seen as outpatient by mental health specialists, with risk especially high within 26 weeks of visits. An elastic net classifier with 10-14 predictors optimized sensitivity (45.6% of suicide deaths occurring after the 15% of visits with highest predicted risk). Good model stability was found for a model using 2004-2007 data to predict 2008-2009 suicides, although stability decreased in a model using 2008-2009 data to predict 2010-2012 suicides. The 5% of visits with highest risk included only 0.1% of soldiers (1047.1 suicides/100 000 person-years in the 5 weeks after the visit). This is a high enough concentration of risk to have implications for targeting preventive interventions. An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk mandated by the VA/DoD CPG to be recorded
Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA
In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action
The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.Methods: A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes ( birth weight, small for gestational age and preterm births), in a two-level hierarchical model.Results: We found effects of both individual ( education, race, prenatal care index) and area-based ( median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income.Conclusion: Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.This work is supported by the Harvard Environmental Protection Agency (EPA) Center,
Grants R827353 and R-832416, and National Institute for Environmental Health Science (NIEHS) ES-0002
The cardiac work-loop technique:An in vitro model for identifying and profiling drug-induced changes in inotropy using rat papillary muscles
Turbulence and galactic structure
Interstellar turbulence is driven over a wide range of scales by processes
including spiral arm instabilities and supernovae, and it affects the rate and
morphology of star formation, energy dissipation, and angular momentum transfer
in galaxy disks. Star formation is initiated on large scales by gravitational
instabilities which control the overall rate through the long dynamical time
corresponding to the average ISM density. Stars form at much higher densities
than average, however, and at much faster rates locally, so the slow average
rate arises because the fraction of the gas mass that forms stars at any one
time is low, ~10^{-4}. This low fraction is determined by turbulence
compression, and is apparently independent of specific cloud formation
processes which all operate at lower densities. Turbulence compression also
accounts for the formation of most stars in clusters, along with the cluster
mass spectrum, and it gives a hierarchical distribution to the positions of
these clusters and to star-forming regions in general. Turbulent motions appear
to be very fast in irregular galaxies at high redshift, possibly having speeds
equal to several tenths of the rotation speed in view of the morphology of
chain galaxies and their face-on counterparts. The origin of this turbulence is
not evident, but some of it could come from accretion onto the disk. Such high
turbulence could help drive an early epoch of gas inflow through viscous
torques in galaxies where spiral arms and bars are weak. Such evolution may
lead to bulge or bar formation, or to bar re-formation if a previous bar
dissolved. We show evidence that the bar fraction is about constant with
redshift out to z~1, and model the formation and destruction rates of bars
required to achieve this constancy.Comment: in: Penetrating Bars through Masks of Cosmic Dust: The Hubble Tuning
Fork strikes a New Note, Eds., K. Freeman, D. Block, I. Puerari, R. Groess,
Dordrecht: Kluwer, in press (presented at a conference in South Africa, June
7-12, 2004). 19 pgs, 5 figure
Holographic Geometry of Entanglement Renormalization in Quantum Field Theories
We study a conjectured connection between the AdS/CFT and a real-space
quantum renormalization group scheme, the multi-scale entanglement
renormalization ansatz (MERA). By making a close contact with the holographic
formula of the entanglement entropy, we propose a general definition of the
metric in the MERA in the extra holographic direction, which is formulated
purely in terms of quantum field theoretical data. Using the continuum version
of the MERA (cMERA), we calculate this emergent holographic metric explicitly
for free scalar boson and free fermions theories, and check that the metric so
computed has the properties expected from AdS/CFT. We also discuss the cMERA in
a time-dependent background induced by quantum quench and estimate its
corresponding metric.Comment: 42pages, 9figures, reference added, minor chang
Nonthermal Emission from Star-Forming Galaxies
The detections of high-energy gamma-ray emission from the nearby starburst
galaxies M82 & NGC253, and other local group galaxies, broaden our knowledge of
star-driven nonthermal processes and phenomena in non-AGN star-forming
galaxies. We review basic aspects of the related processes and their modeling
in starburst galaxies. Since these processes involve both energetic electrons
and protons accelerated by SN shocks, their respective radiative yields can be
used to explore the SN-particle-radiation connection. Specifically, the
relation between SN activity, energetic particles, and their radiative yields,
is assessed through respective measures of the particle energy density in
several star-forming galaxies. The deduced energy densities range from O(0.1)
eV/cm^3 in very quiet environments to O(100) eV/cm^3 in regions with very high
star-formation rates.Comment: 17 pages, 5 figures, to be published in Astrophysics and Space
Science Proceeding
Functional compensation of glutathione S-transferase M1 (GSTM1) null by another GST superfamily member,GSTM2
The gene for glutathione-S-transferase (GST) M1 (GSTM1), a member of the GST-superfamily, is widely studied in cancer risk with regard to the homozygous deletion of the gene (GSTM1 null), leading to a lack of corresponding enzymatic activity. Many of these studies have reported inconsistent findings regarding its association with cancer risk. Therefore, we employed in silico, in vitro, and in vivo approaches to investigate whether the absence of a functional GSTM1 enzyme in a null variant can be compensated for by other family members. Through the in silico approach, we identified maximum structural homology between GSTM1 and GSTM2. Total plasma GST enzymatic activity was similar in recruited individuals, irrespective of their GSTM1 genotype (positive/null). Furthermore, expression profiling using real-time PCR, western blotting,
and GSTM2 overexpression following transient knockdown of GSTM1 in HeLa cells confirmed that the absence of GSTM1 activity can be compensated for by the overexpression of GSTM
Patients’ Perceptions of Memory Functioning Before and After Surgical Intervention to Treat Medically Refractory Epilepsy.
Purpose:One risk associated with epilepsy surgery is memory loss, but perhaps more important is how patients perceive changes in their memories. This longitudinal study evaluated changes in memory self-reports and investigated how self-reports relate to changes on objective memory measures in temporal or extratemporal epilepsy patients who underwent surgery.
Methods: Objective memory (Wechsler Memory Scale–Revised) and subjective memory self-reports (Memory Assessment Clinics Self-Rating Scale) were individually assessed for 136 patients ∼6 months before and 6 months after surgery. A measure of depressive affect (Beck Depression Inventory–2nd Edition) was used to control variance attributable to emotional distress.
Results: Despite a lack of significant correlational relationships between objective and subjective memory for the entire sample, significant correlations between objective memory scores and self-reports did emerge for a subset of patients who evidenced memory decline. Differences also were found in the subjective memory ratings of temporal lobe versus extratemporal patients. Temporal lobe patients rated their memories more negatively than did extratemporal patients and were more likely to report significant improvements in their memory after surgery.
Conclusions: In general, patients were not accurate when rating their memories compared to other adults. However, patients with significant declines in their memories were sensitive to actual changes in their memories over time relative to their own personal baselines
Boundaries of Semantic Distraction: Dominance and Lexicality Act at Retrieval
Three experiments investigated memory for semantic information with the goal of determining boundary conditions for the manifestation of semantic auditory distraction. Irrelevant speech disrupted the free recall of semantic category-exemplars to an equal degree regardless of whether the speech coincided with presentation or test phases of the task (Experiment 1) and occurred regardless of whether it comprised random words or coherent sentences (Experiment 2). The effects of background speech were greater when the irrelevant speech was semantically related to the to-be-remembered material, but only when the irrelevant words were high in output dominance (Experiment 3). The implications of these findings in relation to the processing of task material and the processing of background speech is discussed
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