2-(4-Chloro­benzo­yl)-1-(diamino­methyl­ene)hydrazinium chloride monohydrate

In the cation of the title compound, C8H10ClN4O+·Cl−·H2O, the guanidinium group is planar (maximum deviation = 0.0001 Å) and nearly perpendicular to carboxamide group, making a dihedral angle of 87.0 (3)°. The N atoms of the guanidine fragment have a planar trigonal configuration and the N atom of the carboxamide group adopts a pyramidal configuration. In the crystal structure, inter­molecular N—H⋯O, N—H⋯Cl and O—H⋯Cl hydrogen bonds link the cations, anions and water mol­ecules into layers parallel to the bc plane

The Expression of PHOSPHO1, nSMase2 and TNAP is Coordinately Regulated by Continuous PTH Exposure in Mineralising Osteoblast Cultures

Sustained exposure to high levels of parathyroid hormone (PTH), as observed in hyperparathyroidism, are catabolic to bone. The increase in the RANKL/OPG ratio in response to continuous PTH, resulting in increased osteoclastogenesis is well established. However, the effects of prolonged PTH exposure on key regulators of skeletal mineralisation has yet to be investigated. This study sought to examine the temporal expression of PHOSPHO1, TNAP and nSMase2 in mineralising osteoblast-like cell cultures and to investigate the effects of continuous PTH exposure on the expression of these genes in vitro. PHOSPHO1, nSMase2 and TNAP expression in cultured MC3T3-C14 cells significantly increased from day 0 to day 10. PTH induced a rapid downregulation of Phospho1 and Smpd3 gene expression in MC3T3-C14 cells and cultured hemi-calvariae. Alpl was differentially regulated by PTH, displaying upregulation in cultured MC3T3-C14 cells and downregulation in hemi-calvariae. The effects of PTH on Phospho1 expression were mimicked with the cAMP agonist forskolin, and blocked by the PKA inhibitor PKI (5-24), highlighting a role for the cAMP/PKA pathway in this regulation. The potent down-regulation of Phospho1 and Smpd3 in osteoblasts in response to continuous PTH may provide a novel explanation for the catabolic effects on the skeleton of such an exposure. Furthermore, our findings support the hypothesis that PHOSPHO1, nSMase2 and TNAP function cooperatively in the initiation of skeletal mineralisation

Regularizing Portfolio Optimization

The optimization of large portfolios displays an inherent instability to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification "pressure". This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade-off between the two, depending on the size of the available data set

Diffusion of e-health innovations in 'post-conflict' settings: a qualitative study on the personal experiences of health workers.

BACKGROUND: Technological innovations have the potential to strengthen human resources for health and improve access and quality of care in challenging 'post-conflict' contexts. However, analyses on the adoption of technology for health (that is, 'e-health') and whether and how e-health can strengthen a health workforce in these settings have been limited so far. This study explores the personal experiences of health workers using e-health innovations in selected post-conflict situations. METHODS: This study had a cross-sectional qualitative design. Telephone interviews were conducted with 12 health workers, from a variety of cadres and stages in their careers, from four post-conflict settings (Liberia, West Bank and Gaza, Sierra Leone and Somaliland) in 2012. Everett Roger's diffusion of innovation-decision model (that is, knowledge, persuasion, decision, implementation, contemplation) guided the thematic analysis. RESULTS: All health workers interviewed held positive perceptions of e-health, related to their beliefs that e-health can help them to access information and communicate with other health workers. However, understanding of the scope of e-health was generally limited, and often based on innovations that health workers have been introduced through by their international partners. Health workers reported a range of engagement with e-health innovations, mostly for communication (for example, email) and educational purposes (for example, online learning platforms). Poor, unreliable and unaffordable Internet was a commonly mentioned barrier to e-health use. Scaling-up existing e-health partnerships and innovations were suggested starting points to increase e-health innovation dissemination. CONCLUSIONS: Results from this study showed ICT based e-health innovations can relieve information and communication needs of health workers in post-conflict settings. However, more efforts and investments, preferably driven by healthcare workers within the post-conflict context, are needed to make e-health more widespread and sustainable. Increased awareness is necessary among health professionals, even among current e-health users, and physical and financial access barriers need to be addressed. Future e-health initiatives are likely to increase their impact if based on perceived health information needs of intended users

Impact of age norms and stereotypes on managers' hiring decisions of retirees

Purpose -Our study investigates the role of managers in the re-employment of early retirees and asks what the effect is of managers’ age norms and stereotypes on managers’ employment decisions. Design/methodology/approach- A combination of a factorial study and a survey was conducted. First, information on the age norms and stereotypes was collected. Secondly, profiles of hypothetical retired job applicants were presented to the employers, who were asked to make a specific hiring decision. The information collected during both studies was combined in the analysis and multilevel models were estimated. Findings -The results indicate that higher age norms result in a higher propensity to hire an early retiree. Stereotypes, by contrast, do not influence managers’ decisions. Early retirees’ chances for re-employment are also related to their own circumstances (physical appearance and relevant experience) and organisational forces, as they are hired when organisations face labour force shortages. Research limitation / implications – with the use of vignettes study we deal with hypothetical hiring situation. Originality value- Although the effect of age norms and age stereotypes has been often suggested, not much empirical evidence was presented to support this notion. Our study estimates the effect of age norms and stereotypes on hiring decision. key words: bridge employment; early retirees; age norms; age stereotypes; multilevel models.

MEPE is a novel regulator of growth plate cartilage mineralization

Matrix extracellular phosphoglycoprotein (MEPE) belongs to the SIBLING protein family which play key roles in biomineralization. Although the growth plates of MEPE-overexpressing mice display severe morphological disruption, the expression and function of MEPE in growth plate matrix mineralization remains largely undefined. Here we show MEPE and its cleavage product, the acidic serine aspartate-rich MEPE-associated motif (ASARM) peptide, to be localised to the hypertrophic zone of the growth plate. We also demonstrate that the phosphorylated (p)ASARM peptide inhibits ATDC5 chondrocyte matrix mineralization. Stable MEPE-overexpressing ATDC5 cells also had significantly reduced matrix mineralization in comparison to the control cells. Interestingly, we show that the addition of the non-phosphorylated (np)ASARM peptide promoted mineralization in the ATDC5 cells. The peptides and the overexpression of MEPE did not affect the differentiation of the ATDC5 cells. For a more physiologically relevant model, we utilized the metatarsal organ culture model. We show the pASARM peptide to inhibit mineralization at two stages of development, as shown by histological and ?CT analysis. Like in the ATDC5 cells, the peptides did not affect the differentiation of the metatarsals indicating that the effects seen on mineralization are direct, as is additionally confirmed by no change in alkaline phosphatase activity or mRNA expression. In the metatarsal organ cultures, the pASARM peptide also reduced endothelial cell markers and vascular endothelial growth factor mRNA expression. Taken together these results show MEPE to be an important regulator of growth plate chondrocyte matrix mineralization through its cleavage to an ASARM peptide

A multinuclear solid state NMR, density functional theory and X-Ray diffraction study of hydrogen bonding in Group I hydrogen dibenzoates

An NMR crystallographic approach incorporating multinuclear solid state NMR (SSNMR), X-ray structure determinations and density functional theory (DFT) are used to characterise the H bonding arrangements in benzoic acid (BZA) and the corresponding Group I alkali metal hydrogen dibenzoates (HD) systems. Since the XRD data often cannot precisely confirm the proton position within the hydrogen bond, the relationship between the experimental SSNMR parameters and the ability of gauge included plane augmented wave (GIPAW) DFT to predict them becomes a powerful constraint that can assist with further structure refinement. Both the 1H and 13C MAS NMR methods provide primary descriptions of the H bonding via accurate measurements of the 1H and 13C isotropic chemical shifts, and the individual 13C chemical shift tensor elements; these are unequivocally corroborated by DFT calculations, which together accurately describe the trend of the H bonding strength as the size of the monovalent cation changes. In addition, 17O MAS and DOR NMR form a powerful combination to characterise the O environments, with the DOR technique providing highly resolved 17O NMR data which helps verify unequivocally the number of inequivalent O positions for the conventional 17O MAS NMR to process. Further multinuclear MAS and static NMR studies involving the quadrupolar 7Li, 39K, 87Rb and 133Cs nuclei, and the associated DFT calculations, provide trends and a corroboration of the H bond geometry which assist in the understanding of these arrangements. Even though the crystallographic H positions in each H bonding arrangement reported from the single crystal X-ray studies are prone to uncertainty, the good corroboration between the measured and DFT calculated chemical shift and quadrupole tensor parameters for the Group I alkali species suggest that these reported H positions are reliable

Evidence-based practice educational intervention studies: A systematic review of what is taught and how it is measured

Abstract Background Despite the established interest in evidence-based practice (EBP) as a core competence for clinicians, evidence for how best to teach and evaluate EBP remains weak. We sought to systematically assess coverage of the five EBP steps, review the outcome domains measured, and assess the properties of the instruments used in studies evaluating EBP educational interventions. Methods We conducted a systematic review of controlled studies (i.e. studies with a separate control group) which had investigated the effect of EBP educational interventions. We used citation analysis technique and tracked the forward and backward citations of the index articles (i.e. the systematic reviews and primary studies included in an overview of the effect of EBP teaching) using Web of Science until May 2017. We extracted information on intervention content (grouped into the five EBP steps), and the outcome domains assessed. We also searched the literature for published reliability and validity data of the EBP instruments used. Results Of 1831 records identified, 302 full-text articles were screened, and 85 included. Of these, 46 (54%) studies were randomised trials, 51 (60%) included postgraduate level participants, and 63 (75%) taught medical professionals. EBP Step 3 (critical appraisal) was the most frequently taught step (63 studies; 74%). Only 10 (12%) of the studies taught content which addressed all five EBP steps. Of the 85 studies, 52 (61%) evaluated EBP skills, 39 (46%) knowledge, 35 (41%) attitudes, 19 (22%) behaviours, 15 (18%) self-efficacy, and 7 (8%) measured reactions to EBP teaching delivery. Of the 24 instruments used in the included studies, 6 were high-quality (achieved ≥3 types of established validity evidence) and these were used in 14 (29%) of the 52 studies that measured EBP skills; 14 (41%) of the 39 studies that measured EBP knowledge; and 8 (26%) of the 35 studies that measured EBP attitude. Conclusions Most EBP educational interventions which have been evaluated in controlled studies focus on teaching only some of the EBP steps (predominantly critically appraisal of evidence) and did not use high-quality instruments to measure outcomes. Educational packages and instruments which address all EBP steps are needed to improve EBP teaching