Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample

BACKGROUND: The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use. METHOD: We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD. RESULTS: Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes. CONCLUSIONS: The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs

RCS2 J232727.6-020437: An Efficient Cosmic Telescope at z=0.6986z=0.6986

We present a detailed gravitational lens model of the galaxy cluster RCS2 J232727.6-020437. Due to cosmological dimming of cluster members and ICL, its high redshift ($z=0.6986$) makes it ideal for studying background galaxies. Using new ACS and WFC3/IR HST data, we identify 16 multiple images. From MOSFIRE follow up, we identify a strong emission line in the spectrum of one multiple image, likely confirming the redshift of that system to $z=2.083$. With a highly magnified ($\mu\gtrsim2$) source plane area of $\sim0.7$ arcmin$^2$ at $z=7$, RCS2 J232727.6-020437 has a lensing efficiency comparable to the Hubble Frontier Fields clusters. We discover four highly magnified $z\sim7$ candidate Lyman-break galaxies behind the cluster, one of which may be multiply-imaged. Correcting for magnification, we find that all four galaxies are fainter than $0.5 L_{\star}$. One candidate is detected at ${>10\sigma}$ in both Spitzer/IRAC [3.6] and [4.5] channels. A spectroscopic follow-up with MOSFIRE does not result in the detection of the Lyman-alpha emission line from any of the four candidates. From the MOSFIRE spectra we place median upper limits on the Lyman-alpha flux of $5-14 \times 10^{-19}\, \mathrm{erg \,\, s^{-1} cm^{-2}}$ ($5\sigma$).Comment: 14 pages, 9 figures, submitted to ApJ on 3/06/201

Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.

Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans

On Vanishing Theorems For Vector Bundle Valued p-Forms And Their Applications

Let $F: [0, \infty) \to [0, \infty)$ be a strictly increasing $C^2$ function with $F(0)=0$. We unify the concepts of $F$-harmonic maps, minimal hypersurfaces, maximal spacelike hypersurfaces, and Yang-Mills Fields, and introduce $F$-Yang-Mills fields, $F$-degree, $F$-lower degree, and generalized Yang-Mills-Born-Infeld fields (with the plus sign or with the minus sign) on manifolds. When $F(t)=t, \frac 1p(2t)^{\frac p2}, \sqrt{1+2t} -1,$ and $1-\sqrt{1-2t},$ the $F$-Yang-Mills field becomes an ordinary Yang-Mills field, $p$-Yang-Mills field, a generalized Yang-Mills-Born-Infeld field with the plus sign, and a generalized Yang-Mills-Born-Infeld field with the minus sign on a manifold respectively. We also introduce the $E_{F,g}-$energy functional (resp. $F$-Yang-Mills functional) and derive the first variational formula of the $E_{F,g}-$energy functional (resp. $F$-Yang-Mills functional) with applications. In a more general frame, we use a unified method to study the stress-energy tensors that arise from calculating the rate of change of various functionals when the metric of the domain or base manifold is changed. These stress-energy tensors, linked to $F$-conservation laws yield monotonicity formulae. A "macroscopic" version of these monotonicity inequalities enables us to derive some Liouville type results and vanishing theorems for $p-$forms with values in vector bundles, and to investigate constant Dirichlet boundary value problems for 1-forms. In particular, we obtain Liouville theorems for $F-$harmonic maps (e.g. $p$-harmonic maps), and $F-$Yang-Mills fields (e.g. generalized Yang-Mills-Born-Infeld fields on manifolds). We also obtain generalized Chern type results for constant mean curvature type equations for $p-$forms on $\Bbb{R}^m$ and on manifolds $M$ with the global doubling property by a different approach. The case $p=0$ and $M=\mathbb{R}^m$ is due to Chern.Comment: 1. This is a revised version with several new sections and an appendix that will appear in Communications in Mathematical Physics. 2. A "microscopic" approach to some of these monotonicity formulae leads to celebrated blow-up techniques and regularity theory in geometric measure theory. 3. Our unique solution of the Dirichlet problems generalizes the work of Karcher and Wood on harmonic map

Multidisciplinary outpatient care program for patients with chronic low back pain: design of a randomized controlled trial and cost-effectiveness study [ISRCTN28478651]

<p>Abstract</p> <p>Background</p> <p>Chronic low back pain (LBP) is a major public and occupational health problem, which is associated with very high costs. Although medical costs for chronic LBP are high, most costs are related to productivity losses due to sick leave. In general, the prognosis for return to work (RTW) is good but a minority of patients will be absent long-term from work. Research shows that work related problems are associated with an increase in seeking medical care and sick leave. Usual medical care of patients is however, not specifically aimed at RTW.</p> <p>The objective is to present the design of a randomized controlled trial, i.e. the BRIDGE-study, evaluating the effectiveness in improving RTW and cost-effectiveness of a multidisciplinary outpatient care program situated in both primary and outpatient care setting compared with usual clinical medical care for patients with chronic LBP.</p> <p>Methods/Design</p> <p>The design is a randomized controlled trial with an economic evaluation alongside. The study population consists of patients with chronic LBP who are completely or partially sick listed and visit an outpatient clinic of one of the participating hospitals in Amsterdam (the Netherlands). Two interventions will be compared. 1. a multidisciplinary outpatient care program consisting of a workplace intervention based on participatory ergonomics, and a graded activity program using cognitive behavioural principles. 2. usual care provided by the medical specialist, the occupational physician, the patient's general practitioner and allied health professionals. The primary outcome measure is sick leave duration until full RTW. Sick leave duration is measured monthly by self-report during one year. Data on sick leave during one-year follow-up are also requested form the employers. Secondary outcome measures are pain intensity, functional status, pain coping, patient satisfaction and quality of life. Outcome measures are assessed before randomization and 3, 6, and 12 months later. All statistical analysis will be performed according to the intension-to-treat principle.</p> <p>Discussion</p> <p>Usual care of primary and outpatient health services isn't directly aimed at RTW, therefor it is desirable to look for care which is aimed at RTW. Research shows that several occupational interventions in primary care are aimed at RTW. They have shown a significant reduction of sick leave for employee with LBP. If a comparable reduction of sick leave duration of patients with chronic LBP of who attend an outpatient clinic can be achieved, such reductions will be obviously substantial for the Netherlands and will have a considerable impact.</p> <p>Trial registration</p> <p>ISRCTN28478651</p

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Reliability of infrared thermography in skin temperature evaluation of wheelchair users

To examine the reliability of infrared thermography (IRT) in wheelchair users (WCUs), as a noninvasive and risk-free technique to detect the natural thermal radiation emitted by human skin and to allow subsequent interpretations of temperature distributions

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Nanostructured Silver Substrates With Stable and Universal SERS Properties: Application to Organic Molecules and Semiconductor Nanoparticles

Nanostructured silver films have been prepared by thermal deposition on silicon, and their properties as SERS substrates investigated. The optimal conditions of the post-growth annealing of the substrates were established. Atomic force microscopy study revealed that the silver films with relatively dense and homogeneous arrays of 60–80-nm high pyramidal nanoislands are the most efficient for SERS of both organic dye and inorganic nanoparticles analytes. The noticeable enhancement of the Raman signal from colloidal nanoparticles with the help of silver island films is reported for the first time