A comparison of walk-in counselling and the wait list model for delivering counselling services

Background: Walk-in counselling has been used to reduce wait times but there are few controlled studies to compare outcomes between walk-in and the traditional model of service delivery. Aims: To compare change in psychological distress by clients receiving services from two models of service delivery, a walk-in counselling model and a traditional counselling model involving a wait list Method: Mixed methods sequential explanatory design including quantitative comparison of groups with one pre-test and two follow ups, and qualitative analysis of interviews with a subsample. 524 participants 16 years and older were recruited from two Family Counselling Agencies; the General Health Questionnaire assessed change in psychological distress; prior use of other mental health and instrumental services was also reported. Results: Hierarchical linear modelling revealed clients of the walk-in model improved faster and were less distressed at the 4-week follow-up compared to the traditional service delivery model. At the 10-week follow-up, both groups had improved and were similar. Participants receiving instrumental services prior to baseline improved more slowly. Qualitative interviews confirmed participants valued the accessibility of the walk-in model. Conclusions: This study improves methodologically on previous studies of walk-in counselling, an approach to service delivery that is not conducive to randomized controlled trials

On the discovery of continuous truth: a semi-supervised approach with partial ground truths

In many applications, the information regarding to the same object can be collected from multiple sources. However, these multi-source data are not reported consistently. In the light of this challenge, truth discovery is emerged to identify truth for each object from multi-source data. Most existing truth discovery methods assume that ground truths are completely unknown, and they focus on the exploration of unsupervised approaches to jointly estimate object truths and source reliabilities. However, in many real world applications, a set of ground truths could be partially available. In this paper, we propose a semi-supervised truth discovery framework to estimate continuous object truths. With the help of ground truths, even a small amount, the accuracy of truth discovery can be improved. We formulate the semi-supervised truth discovery problem as an optimization task where object truths and source reliabilities are modeled as variables. The ground truths are modeled as a regularization term and its contribution to the source weight estimation can be controlled by a parameter. The experiments show that the proposed method is more accurate and efficient than the existing truth discovery methods

The connection between superconducting phase correlations and spin excitations in YBa2_2Cu3_3O6.6_{6.6}: A magnetic field study

One of the most striking universal properties of the high-transition-temperature (high-$T_c$) superconductors is that they are all derived from the hole-doping of their insulating antiferromagnetic (AF) parent compounds. From the outset, the intimate relationship between magnetism and superconductivity in these copper-oxides has intrigued researchers. Evidence for this link comes from neutron scattering experiments that show the unambiguous presence of short-range AF correlations (excitations) in cuprate superconductors. Even so, the role of such excitations in the pairing mechanism and superconductivity is still a subject of controversy. For YBa$_2$Cu$_3$O$_{6+x}$, where $x$ controls the hole-doping level, the most prominent feature in the magnetic excitations spectra is the ``resonance''. Here we show that for underdoped YBa$_2$Cu$_3$O$_{6.6}$, where $x$ and $T_c$ are below the optimal values, modest magnetic fields suppress the resonance significantly, much more so for fields approximately perpendicular rather than parallel to the CuO$_2$ planes. Our results indicate that the resonance measures pairing and phase coherence, suggesting that magnetism plays an important role in the superconductivity of cuprates. The persistence of a field effect above $T_c$ favors mechanisms with preformed pairs in the normal state of underdoped cuprates.Comment: 12 pages, 4 figures, Nature (in press

Peptidases compartmentalized to the Ascaris suum intestinal lumen and apical intestinal membrane

The nematode intestine is a tissue of interest for developing new methods of therapy and control of parasitic nematodes. However, biological details of intestinal cell functions remain obscure, as do the proteins and molecular functions located on the apical intestinal membrane (AIM), and within the intestinal lumen (IL) of nematodes. Accordingly, methods were developed to gain a comprehensive identification of peptidases that function in the intestinal tract of adult female Ascaris suum. Peptidase activity was detected in multiple fractions of the A. suum intestine under pH conditions ranging from 5.0 to 8.0. Peptidase class inhibitors were used to characterize these activities. The fractions included whole lysates, membrane enriched fractions, and physiological- and 4 molar urea-perfusates of the intestinal lumen. Concanavalin A (ConA) was confirmed to bind to the AIM, and intestinal proteins affinity isolated on ConA-beads were compared to proteins from membrane and perfusate fractions by mass spectrometry. Twenty-nine predicted peptidases were identified including aspartic, cysteine, and serine peptidases, and an unexpectedly high number (16) of metallopeptidases. Many of these proteins co-localized to multiple fractions, providing independent support for localization to specific intestinal compartments, including the IL and AIM. This unique perfusion model produced the most comprehensive view of likely digestive peptidases that function in these intestinal compartments of A. suum, or any nematode. This model offers a means to directly determine functions of these proteins in the A. suum intestine and, more generally, deduce the wide array functions that exist in these cellular compartments of the nematode intestine

Novel regulators of PrPC biosynthesis revealed by genome-wide RNA interference

The cellular prion protein PrPC is necessary for prion replication, and its reduction greatly increases life expectancy in animal models of prion infection. Hence the factors controlling the levels of PrPC may represent therapeutic targets against human prion diseases. Here we performed an arrayed whole-transcriptome RNA interference screen to identify modulators of PrPC expression. We cultured human U251-MG glioblastoma cells in the presence of 64'752 unique siRNAs targeting 21'584 annotated human genes, and measured PrPC using a one-pot fluorescence-resonance energy transfer immunoassay in 51'128 individual microplate wells. This screen yielded 743 candidate regulators of PrPC. When downregulated, 563 of these candidates reduced and 180 enhanced PrPC expression. Recursive candidate attrition through multiple secondary screens yielded 54 novel regulators of PrPC, 9 of which were confirmed by CRISPR interference as robust regulators of PrPC biosynthesis and degradation. The phenotypes of 6 of the 9 candidates were inverted in response to transcriptional activation using CRISPRa. The RNA-binding post-transcriptional repressor Pumilio-1 was identified as a potent limiter of PrPC expression through the degradation of PRNP mRNA. Because of its hypothesis-free design, this comprehensive genetic-perturbation screen delivers an unbiased landscape of the genes regulating PrPC levels in cells, most of which were unanticipated, and some of which may be amenable to pharmacological targeting in the context of antiprion therapies

An Electron Fixed Target Experiment to Search for a New Vector Boson A' Decaying to e+e-

We describe an experiment to search for a new vector boson A' with weak coupling alpha' > 6 x 10^{-8} alpha to electrons (alpha=e^2/4pi) in the mass range 65 MeV < m_A' < 550 MeV. New vector bosons with such small couplings arise naturally from a small kinetic mixing of the "dark photon" A' with the photon -- one of the very few ways in which new forces can couple to the Standard Model -- and have received considerable attention as an explanation of various dark matter related anomalies. A' bosons are produced by radiation off an electron beam, and could appear as narrow resonances with small production cross-section in the trident e+e- spectrum. We summarize the experimental approach described in a proposal submitted to Jefferson Laboratory's PAC35, PR-10-009. This experiment, the A' Experiment (APEX), uses the electron beam of the Continuous Electron Beam Accelerator Facility at Jefferson Laboratory (CEBAF) at energies of ~1-4 GeV incident on 0.5-10% radiation length Tungsten wire mesh targets, and measures the resulting e+e- pairs to search for the A' using the High Resolution Spectrometer and the septum magnet in Hall A. With a ~1 month run, APEX will achieve very good sensitivity because the statistics of e+e- pairs will be ~10,000 times larger in the explored mass range than any previous search for the A' boson. These statistics and the excellent mass resolution of the spectrometers allow sensitivity to alpha'/alpha one to three orders of magnitude below current limits, in a region of parameter space of great theoretical and phenomenological interest. Similar experiments could also be performed at other facilities, such as the Mainz Microtron.Comment: 19 pages, 12 figures, 2 table

Dark Force Detection in Low Energy e-p Collisions

We study the prospects for detecting a light boson X with mass m_X < 100 MeV at a low energy electron-proton collider. We focus on the case where X dominantly decays to e+ e- as motivated by recent "dark force" models. In order to evade direct and indirect constraints, X must have small couplings to the standard model (alpha_X 10 MeV). By comparing the signal and background cross sections for the e- p e+ e- final state, we conclude that dark force detection requires an integrated luminosity of around 1 inverse attobarn, achievable with a forthcoming JLab proposal.Comment: 38 pages, 19 figures; v2, references adde

Decaying into the Hidden Sector

The existence of light hidden sectors is an exciting possibility that may be tested in the near future. If DM is allowed to decay into such a hidden sector through GUT suppressed operators, it can accommodate the recent cosmic ray observations without over-producing antiprotons or interfering with the attractive features of the thermal WIMP. Models of this kind are simple to construct, generic and evade all astrophysical bounds. We provide tools for constructing such models and present several distinct examples. The light hidden spectrum and DM couplings can be probed in the near future, by measuring astrophysical photon and neutrino fluxes. These indirect signatures are complimentary to the direct production signals, such as lepton jets, predicted by these models.Comment: 40 pages, 5 figure

Use of Site-Specifically Tethered Chemical Nucleases to Study Macromolecular Reactions

During a complex macromolecular reaction multiple changes in molecular conformation and interactions with ligands may occur. X-ray crystallography may provide only a limited set of snapshots of these changes. Solution methods can augment such structural information to provide a more complete picture of a macromolecular reaction. We analyzed the changes in protein conformation and protein:nucleic acid interactions which occur during transcription initiation by using a chemical nuclease tethered to cysteines introduced site-specifically into the RNA polymerase of bacteriophage T7 (T7 RNAP). Changes in cleavage patterns as the polymerase steps through transcription reveal a series of structural transitions which mediate transcription initiation. Cleavage by tethered chemical nucleases is seen to be a powerful method for revealing the conformational dynamics of macromolecular reactions, and has certain advantages over cross-linking or energy transfer approaches