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Health system data incompletely capture the social risk factors for drug overdose. This study aimed to improve the accuracy of a machine-learning algorithm to predict opioid overdose risk by integrating human services and criminal justice data with health claims data to capture the social determinants of overdose risk. This prognostic study included Medicaid beneficiaries (n = 237,259) in Allegheny County, Pennsylvania enrolled between 2015 and 2018, randomly divided into training, testing, and validation samples. We measured 290 potential predictors (239 derived from Medicaid claims data) in 30-day periods, beginning with the first observed Medicaid enrollment date during the study period. Using a gradient boosting machine, we predicted a composite outcome (i.e., fatal or nonfatal opioid overdose constructed using medical examiner and claims data) in the subsequent month. We compared prediction performance between a Medicaid claims only model to one integrating human services and criminal justice data with Medicaid claims (i.e., integrated model) using several metrics (e.g., C-statistic, number needed to evaluate [NNE] to identify one overdose). Beneficiaries were stratified into risk-score decile subgroups. The samples (training = 79,087, testing = 79,086, validation = 79,086) had similar characteristics (age = 38±18 years, female = 56%, white = 48%, having at least one overdose = 1.7% during study period). Using the validation sample, the integrated model slightly improved on the Medicaid claims only model (C-statistic = 0.885; 95%CI = 0.877–0.892 vs. C-statistic = 0.871; 95%CI = 0.863–0.878), with small corresponding improvements in the NNE and positive predictive value. Nine of the top 30 most important predictors in the integrated model were human services and criminal justice variables. Using the integrated model, approximately 70% of individuals with overdoses were members of the top risk decile (overdose rates in the subsequent month = 47/10,000 beneficiaries). Few individuals in the bottom 9 deciles had overdose episodes (0-12/10,000). Machine-learning algorithms integrating claims and social service and criminal justice data modestly improved opioid overdose prediction among Medicaid beneficiaries for a large U.S. county heavily affected by the opioid crisis.

Innovative vaccines against typhoid and other Salmonella diseases that are safe, effective, and inexpensive are urgently needed. In order to address this need, buoyant, self-adjuvating gas vesicle nanoparticles (GVNPs) from the halophilic archaeon Halobacterium sp. NRC-1 were bioengineered to display the highly conserved Salmonella enterica antigen SopB, a secreted inosine phosphate effector protein injected by pathogenic bacteria during infection into the host cell. Two highly conserved sopB gene segments near the 3'-coding region, named sopB4 and B5, were each fused to the gvpC gene, and resulting GVNPs were purified by centrifugally accelerated flotation. Display of SopB4 and B5 antigenic epitopes on GVNPs was established by Western blotting analysis using antisera raised against short synthetic peptides of SopB. Immunostimulatory activities of the SopB4 and B5 nanoparticles were tested by intraperitoneal administration of recombinant GVNPs to BALB/c mice which had been immunized with S. enterica serovar Typhimurium 14028 Delta pmrG-HM-D (DV-STM-07), a live attenuated vaccine strain. Proinflammatory cytokines IFN-gamma, IL-2, and IL-9 were significantly induced in mice boosted with SopB5-GVNPs, consistent with a robust Th1 response. After challenge with virulent S. enterica serovar Typhimurium 14028, bacterial burden was found to be diminished in spleen of mice boosted with SopB4-GVNPs and absent or significantly diminished in liver, mesenteric lymph node, and spleen of mice boosted with SopB5-GVNPs, indicating that the C-terminal portions of SopB displayed on GVNPs elicit a protective response to Salmonella infection in mice. SopB antigen-GVNPs were found to be stable at elevated temperatures for extended periods without refrigeration in Halobacterium cells. The results all together show that bioengineered GVNPs are likely to represent a valuable platform for the development of improved vaccines against Salmonella diseases. (C) 2014 Elsevier Ltd. All rights reserved.

Four guiding principles are suggested to teaching librarians as ways to frame the conversations with ourselves, our partners in the academy, and with our students. True collaboration happens as a consequence of good conversations. Conversations take time, patience, the ability to listen, and the ability to change.

The identification of antigenic targets in the retroocular autoimmune response of Graves' ophthalmopathy is likely to increase our understanding of mechanisms underlying this disorder. While a number of putative autoantigens have been identified on the basis of molecular weight or cell of origin, a determination of the significance of these antigens is contingent upon an identification of the amino acid sequence. Our group has previously identified immunoreactive retroocular fibroblast (ROF) proteins recognized by thyrotropin receptor (hTSH-R) antisera (anti-p1), at molecular weights of 95, 71, 41, and 14-25 kDa. In the present study, proteins detected by anti-p1 and visualized by Ponceau staining were isolated and processed for microsequencing. Ponceau staining revealed dense bands at molecular weights of 14 and 23 kDa, and a weak band at 41 kDa. N-terminal sequencing was performed on the prominent band at approximately 23 kDa, showing it to be manganese superoxide dismutase (MnSOD), a mitochondrial enzyme responsible for protection against oxygen free radical-associated cellular damage. Sequence comparison of MnSOD to the hTSH-R peptide, p1, revealed a linear segment of amino acid homology. Preincubation of anti-p1 with p1 blocked immunodetection of the 23 kDa band corresponding to MnSOD, and immunoprecipitation of ROF protein using anti-pi yielded protein recognized by anti-MnSOD. Autoimmunity against human recombinant MnSOD was further assessed by ELISA. Patients with Graves' disease (n = 53) had significantly higher ELISA indices than normal control subjects (n = 29), while patients with Hashimoto's thyroiditis had intermediate values. These results document MnSOD autoantibodies in patients with Graves' disease and suggest that this may result from an immune cross-reactivity between MnSOD and the TSH-receptor.

Retroocular fibroblast proliferation is believed to be a key component in the pathogenesis of Graves' ophthalmopathy. In the present study, we assessed the ability of superoxide radicals, generated using the xanthine oxidase/hypoxanthine system to induce cellular proliferation in cultured human retroocular fibroblasts obtained from two patients with severe Graves' ophthalmopathy and two control patients undergoing corrective eye surgery. In tissue obtained from patients with Graves' ophthalmopathy, fibroblast proliferation, as assessed by [3H]-thymidine incorporation, was induced by superoxide radicals in a dose-dependent manner. Xanthine oxidase or hypoxanthine alone had no proliferative effect, and control retroocular fibroblasts showed no proliferation in response to superoxide generation. Preincubation with the antithyroid drug methimazole, at concentrations ranging from 0-25 microM, prevented superoxide-induced fibroblast proliferation in a dose-response pattern. Preincubation with the xanthine oxidase inhibitor, allopurinol (1.0 mM) or the antioxidant nicotinamide (10 microM) also inhibited superoxide-induced fibroblast proliferation, whereas propylthiouracil (10 microM) had little effect. These studies suggest a pathway through which oxygen free radicals may contribute to the retroocular fibroblast proliferation observed in patients with Graves' ophthalmopathy.

An audit conducted at UHSM identified the need for a pain assessment tool to help identify pain for people with communication difficulties which led to this small study to test the usefulness of the Bolton Pain Assessment Tool (BPAT). BPAT was developed for patients with communication difficulties and includes a section for the family to be involved in the assessment and provide information specifically relating to the individual.The Bolton Pain Assessment Tool has been introduced and used within four clinical areas of the Trust that were identified as having a proportion of patients with communication difficulties, including dementia.This study helps to address some of the recommendations from the National Dementia Strategy (2009) to improve the care provided in Hospital by addressing the need to recognise, assess and manage pain for all patients admitted to hospital.The aim of the proof of concept study was to assess if the BPAT is useful and helps to identify pain in acute clinical areas. Findings are: • All the staff involved in the evaluation agreed that it was easy to use• The time taken was between half a minute and 5 minutes. Mode was 2 minutes • The use of the BPAT facilitated the process of a review and/ or the administration of analgesia to ensure appropriate / adequate pain management for patients with communication difficulties. • There was limited involvement of the family or close carer of an individual with communication difficulties, but when they were asked they provided relevant information to assist in the assessment and management of pain.• Clinical staff in acute care rated the scale as 8 out of 10 and the majority rated it better or a lot better than other pain assessment tools.Future Plans The intention is to extend the use of BPAT across the organisation and collect further data to support its use.

Apres avoir etudie une partie de la litterature professionnelle des bibliothecaires, l'auteur de cet article propose une methode d'enseignement qui reflete son propre style. Quelques termes resument cet enseignement : la passion et l'enthousiasme, l'humour, le contact et la collectivite, et les etudiants

Distance education is increasingly familiar in higher education, and librarians grapple with ways to effectively reach students who are geographically distant from the main campus and from each other. Although technology has increased access to library resources for many students, using the various systems often poses real obstacles. This paper describes a team-taught research/writing class for adult students who are geographically dispersed across the state. The course is taught in a traditional face-to-face classroom for one weekend and the remainder of the course is conducted over a computer conferencing system. Computer conferencing can supplement and extend human contacts between students and faculty. Linfield College's (Oregon) research/writing class is described, and pros and cons of computer conferencing are discussed.

Autoimmunity against the TSH receptor (hTSH-R) is known to be the proximate cause of thyroidal activation in Graves' disease, but has not been definitively linked to extrathyroidal manifestations of this disorder, such as ophthalmopathy and pretibial myxedema. In an effort to increase our knowledge concerning mechanisms responsible for Graves' ophthalmopathy, we used antiserum directed against a highly immunogenic portion of the hTSH-R (amino acids 352-367; P1) to assess the presence of this receptor or immunologically related protein in cultured human retroocular fibroblasts obtained from patients with Graves' ophthalmopathy. Immunoenzymatic and immunofluorescent studies revealed specific staining of both cytoplasmic and cell membrane-associated protein in discrete vesicles. To further evaluate the immunoreactive species present in these cells, immunoblotting experiments were performed using hTSH-R-specific antisera (anti-P1) and sera obtained from patients with Graves' disease. Several protein bands were identified using both anti-P1 and Graves' disease patient sera, including species at mol wt of 95, 71, and 18 kilodaltons, the possible significance of which is discussed. The results support the hypothesis that immunity against the hTSH-R or related proteins contributes to the ophthalmopathy of Graves' disease.

The Early Aberration Reporting System (EARS) is used by some local health departments (LHDs) to monitor emergency room and clinic data for disease outbreaks. Using actual chief complaint data from local public health clinics, we evaluate how EARS—both the baseline system distributed by the CDC and two variants implemented by one LHD—perform at locally detecting the 2009 influenza A H1N1 pandemic. We also compare the EARS methods to a CUSUM-based method. We find that the baseline EARS system performed poorly in comparison to one of the LHD variants and the CUSUM-based method. These results suggest that changes in how syndromes are defined can substantially improve EARS performance. The results also show that incorporating algorithms that use more historical data will improve EARS performance for routine surveillance by local health departments.

The sulphated octapeptide of cholecystokinin (CCK-8S) was found to cause a dose-dependent increase in the basal release of aspartate, glycine, and gamma-aminobutyric acid from the striatum and the ventromedial nucleus of the hypothalamus (VMH). No effect on amino acid release was observed after electrical (VMH) or potassium (striatum) stimulation. Experiments performed using the CCKB-selective antagonist L-365,260 and the CCKA-selective antagonist L-364,718 suggested that this action of CCK-8S was mediated via the CCKB receptor. The ability of CCK-8S to evoke amino acid release was not dependent on the presence of extracellular calcium, though the effect was abolished by tetrodotoxin. Inhibition of protein kinase activity by staurosporine prevented the excitatory effects of CCK-8S on amino acid release.

Spironolactone and cimetidine are effective antiandrogens in vivo, although they differ by five orders of magnitude in affinity for androgen receptors in vitro. To explore this discrepancy, we directly compared the antiandrogenic potency of these two compounds in vivo using the chicken cockscomb topical bioassay. In this assay, the growth of the androgen sensitive cockscomb of immature chicks after stimulation by various doses of androgen (dihydrotestosterone 5, 20, or 100 micrograms/day sc) is inhibited by antiandrogens in cream vehicle applied topically to the cockscomb itself. At low levels of androgen stimulation (5 micrograms/day), 0.5% topical cimetidine produced maximal suppression of cockscomb growth, while at high levels of androgen stimulation 100 micrograms/day), topical cimetidine in concentrations as high as 4% did not suppress cockscomb growth. In contrast, topical spironolactone in concentrations as low as 0.06% produced maximal inhibition of cockscomb growth at all androgen doses. Using an intermediate androgen dose (20 micrograms/day), the minimally effective antiandrogenic concentration of topical cimetidine was between 0.5 and 1.0%, while that for topical spironolactone was less than 0.001%. We conclude that the chicken cockscomb topical bioassay is a useful method for assessing relative potency of antiandrogens. With this method, spironolactone appears to be at least 500 times as strong an antiandrogen in vivo as cimetidine.

The effects of potassium channel blockade on the spontaneous release of endogenous glutamate from rat cerebellar slices was studied. Tetrapentylammonium (TPeA), 4-aminopyridine and quinine all increased the spontaneous release of glutamate. The effect of TPeA and 4-AP was potentiated in the absence of Ca 2+ from the perfusing fluid. In normal artificial cerebrospinal fluid (ACSF) the Ca 2+ channel antagonist, verapamil, mimicked the effects of TPeA seen in Ca 2+ -free ACSF. The increased release of glutamate produced by TPeA under Ca 2+ -free conditions was inhibited by the sodium channel blocker, tetrodotoxin, and by Ruthenium red, which inhibits mobilizftion of mitochondrialn Ca 2+ . The results suggest that external Ca 2+ is not required in the TPeA-induced release of glutamate. It is proposed that the prolongation of depolarization seen with potassium channel blocking drugs enables sufficient sodium to enter the neurone and release Ca 2+ from intraneuronal stores in order to facilitate transmitter release.

A quasi-experimental, treatment-control group investigation was designed to test the effects of introducing research findings from effective teaching and school leadership into ongoing school settings. Research findings were translated into observable staff developer and teacher behaviors. Following 5 days of training 3 weeks prior to the beginning of school, treatment staff developers implemented self-designed plans to increase effective teaching behaviors. Both staff developers and teachers recorded journal entries, and teachers were observed. Based on staff developer journal entries, a significant treatment effect was found for the transfer of all staff developer behaviors. Based on classroom observations, a significant treatment effect was found for teacher behaviors in 4 of 10 categories of effective teaching behaviors: academic planning and preparation, academic presentation, organizing for classroom management, and presentation of rules and procedures.

Hoffman and his colleagues report the findings from a large scale investigation of two state-mandated beginning teacher programs. The primary goal of their research was to documentthe ways in which beginning teacher programs af fect the transition from student of teach ing to regular classroom teacher. Exten sive data were collected on 16 first year teachers in two states. Data analyses fo cused on the areas of program imple mentation and program effects. The findings are discussed in terms of the research literature on teacher induction and vis-a-vis trends in state policies for teacher certification.

Two new methods of analysing Coulter counter data to give cumulative volume fraction against particle dimension relations are described and discussed together with two previous methods. It is shown that, within the experimental errors possible, there would be no significant difference between the result obtained from the different methods unless reliable mean values are obtained from a large number of runs. In that case one of the new methods would provide a better approximation to the true particle size distribution.

Methods are described for use in the study of potassium-stimulated release of endogenous glutamate and aspartate from perfused cerebellar slices using high performance liquid chromatography (HPLC) with fluorometric detection. Slices were cut at 250 μm in one direction only, and were thus similar to those used for electrophysiological techniques. Details of an easily constructed, simple superfusion system are given. HPLC isocratic separation was used to assay aspartate and glutamate release, glutamate alone showing calcium-dependent release. Repetitive pulses of high potassium-containing artificial cerebrospinal fluid induced release of glutamate (six pulses), demonstrating that the tissue was viable and capable of repeated release.