A Randomized Depression Prevention Trial Comparing Interpersonal Psychotherapy—Adolescent Skills Training To Group Counseling In Schools

Given the rise in depression disorders in adolescence, it is important to develop and study depression prevention programs for this age group. The current study examined the efficacy of Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), a group prevention program for adolescent depression, in comparison to group programs that are typically delivered in school settings. In this indicated prevention trial, 186 adolescents with elevated depression symptoms were randomized to receive IPT-AST delivered by research staff or group counseling (GC) delivered by school counselors. Hierarchical linear modeling examined differences in rates of change in depressive symptoms and overall functioning from baseline to the 6-month follow-up assessment. Cox regression compared rates of depression diagnoses. Adolescents in IPT-AST showed significantly greater improvements in self-reported depressive symptoms and evaluator-rated overall functioning than GC adolescents from baseline to the 6-month follow-up. However, there were no significant differences between the two conditions in onset of depression diagnoses. Although both intervention conditions demonstrated significant improvements in depressive symptoms and overall functioning, results indicate that IPT-AST has modest benefits over groups run by school counselors which were matched on frequency and duration of sessions. In particular, IPT-AST outperformed GC in reduction of depressive symptoms and improvements in overall functioning. These findings point to the clinical utility of this depression prevention program, at least in the short-term. Additional follow-up is needed to determine the long-term effects of IPT-AST, relative to GC, particularly in preventing depression onset

INFLUENCES OF WATERSHED URBANIZATION AND INSTREAM HABITAT ON MACROINVERTEBRATES IN COLD WATER STREAMS 1

We analyzed data from riffle and snag habitats for 39 small cold water streams with different levels of watershed urbanization in Wisconsin and Minnesota to evaluate the influences of urban land use and instream habitat on macroinvertebrate communities. Multivariate analysis indicated that stream temperature and amount of urban land use in the watersheds were the most influential factors determining macroinvertebrate assemblages. The amount of watershed urbanization was nonlinearly and negatively correlated with percentages of Ephemeroptera-Plecoptera-Trichoptera (EPT) abundance, EPT taxa, filterers, and scrapers and positively correlated with Hilsenhoff biotic index. High quality macroinvertebrate index values were possible if effective imperviousness was less than 7 percent of the watershed area. Beyond this level of imperviousness, index values tended to be consistently poor. Land uses in the riparian area were equal or more influential relative to land use elsewhere in the watershed, although riparian area consisted of only a small portion of the entire watershed area. Our study implies that it is extremely important to restrict watershed impervious land use and protect stream riparian areas for reducing human degradation on stream quality in low level urbanizing watersheds. Stream temperature may be one of the major factors through which human activities degrade cold-water streams, and management efforts that can maintain a natural thermal regime will help preserve stream quality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72139/1/j.1752-1688.2003.tb03701.x.pd

Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Four small puzzles that Rosetta doesn't solve

A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular "puzzles" should serve as useful model systems for developers wishing to make foundational improvements to this powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special Collectio

Percutaneous mitral valve edge-to-edge Repair: In-hospital results and 1-year follow-up of 628 patients of the 2011-2012 pilot European Sentinel Registry

The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited

Measurement of the CKM Matrix Element ∣Vcb∣|V_{cb}| from B0→D∗−ℓ+νℓB^{0} \to D^{*-} \ell^+ \nu_\ell at Belle

We present a new measurement of the CKM matrix element $|V_{cb}|$ from $B^{0} \to D^{*-} \ell^+ \nu_\ell$ decays, reconstructed with the full Belle data set of $711 \, \rm fb^{-1}$ integrated luminosity. Two form factor parameterizations, originally conceived by the Caprini-Lellouch-Neubert (CLN) and the Boyd, Grinstein and Lebed (BGL) groups, are used to extract the product $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|$ and the decay form factors, where $\mathcal{F}(1)$ is the normalization factor and $\eta_{\rm EW}$ is a small electroweak correction. In the CLN parameterization we find $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}| = (35.06 \pm 0.15 \pm 0.56) \times 10^{-3}$, $\rho^{2}=1.106 \pm 0.031 \pm 0.007$, $R_{1}(1)=1.229 \pm 0.028 \pm 0.009$, $R_{2}(1)=0.852 \pm 0.021 \pm 0.006$. For the BGL parameterization we obtain $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|= (34.93 \pm 0.23 \pm 0.59)\times 10^{-3}$, which is consistent with the World Average when correcting for $\mathcal{F}(1)\eta_{\rm EW}$. The branching fraction of $B^{0} \to D^{*-} \ell^+ \nu_\ell$ is measured to be $\mathcal{B}(B^{0}\rightarrow D^{*-}\ell^{+}\nu_{\ell}) = (4.90 \pm 0.02 \pm 0.16)\%$. We also present a new test of lepton flavor universality violation in semileptonic $B$ decays, $\frac{{\cal B }(B^0 \to D^{*-} e^+ \nu)}{{\cal B }(B^0 \to D^{*-} \mu^+ \nu)} = 1.01 \pm 0.01 \pm 0.03~$. The errors correspond to the statistical and systematic uncertainties respectively. This is the most precise measurement of $\mathcal{F}(1)\eta_{\rm EW}|V_{cb}|$ and form factors to date and the first experimental study of the BGL form factor parameterization in an experimental measurement

Personalized Feedback on Staff Dose in Fluoroscopy-Guided Interventions: A New Era in Radiation Dose Monitoring

Radiation safety and protection are a key component of fluoroscopy-guided interventions. We hypothesize that providing weekly personal dose feedback will increase radiation awareness and ultimately will lead to optimized behavior. Therefore, we designed and implemented a personalized feedback of procedure and personal doses for medical staff involved in fluoroscopy-guided interventions. Medical staff (physicians and technicians, n = 27) involved in fluoroscopy-guided interventions were equipped with electronic personal dose meters (PDMs). Procedure dose data including the dose area product and effective doses from PDMs were prospectively monitored for each consecutive procedure over an 8-month period (n = 1082). A personalized feedback form was designed displaying for each staff individually the personal dose per procedure, as well as relative and cumulative doses. This study consisted of two phases: (1) 1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months: Staff received weekly individual dose feedback (n = 381). An anonymous evaluation was performed on the feedback and occupational dose. Personalized feedback was scored valuable by 76% of the staff and increased radiation dose awareness for 71%. 57 and 52% reported an increased feeling of occupational safety and changing their behavior because of personalized feedback, respectively. For technicians, the normalized dose was significantly lower in the feedback phase compared to the prefeedback phase: [median (IQR) normalized dose (phase 1) 0.12 (0.04-0.50) A mu Sv/Gy cm(2) versus (phase 2) 0.08 (0.02-0.24) A mu Sv/Gy cm(2), p = 0.002]. Personalized dose feedback increases radiation awareness and safety and can be provided to staff involved in fluoroscopy-guided interventions

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package