Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial

BACKGROUND The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. METHODS The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. DISCUSSION This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. TRIAL REGISTRATION NCT01689077.

The function of socialization in social evolution

Mode of access: Internet.

¿Es su casa mi casa? Latinos, Socialization, and the Catholic Church

Thesis (Ph.D.)--University of Washington, 2016-06

HFE genotyping demonstrates a significant incidence of hemochromatosis in up differentiated arthritis

Objective Hereditary hemochromatosis is a common autosomal recessive disorder of iron metabolism. Among Northern Europeans the carrier frequency is estimated to be I in 10, while up to 1 in 200 is affected by the disease. Arthropathy is one early clinical manifestation of this disease, but the articular features are often misdiagnosed. In this study the two frequent mutations of the HLA-linked hemochromatosis gene (HFE) were investigated, in a rheumatology clinic population. Methods Two hundred and six consecutive patients (mean age 57.7 years; 38 male/168 female) attending a rheumatology clinic over a period of 14 months were screened for HFE mutations (C282Y and H63D). All standard diagnostic procedures were used to identify the aetiology: of the arthropathy. Mutations were evaluated by separation on PAGE of digested PCR amplificates of DNA (by SnapI and Bcl-I, for C282Y and H63D, respectively) obtained from PBMCs. Results The C282Y and H63D allele frequencies were 4.5 and 12.8 inpatients with rheumatic diseases. Five patients were homozygote for H63D (2.4%), and one,for C282Y (0.5%). Five patients were compound heterozygous (2.4%). The observed C282Y allele frequency in rheumatic patients with undifferentiated arthritis was 12.9 and exceeded that of healthy subjects (p = 0.01). Conclusions Determination of the HFE genotype is clinically useful in patients with arthritis of unknown origin, to allow early diagnosis of hemochromatosis.

The role of tissue transglutaminase in 1-methyl-4-phenylpyridinium (MPP+)-induced toxicity in differentiated human SH-SY5Y neuroblastoma cells

Tissue transglutaminase (TG2) can induce post-translational modification of proteins, resulting in protein cross-linking or incorporation of polyamines into substrates, and can also function as a signal transducing G protein. The role of TG2 in the formation of insoluble cross-links has led to its implication in some neurodegenerative conditions. Exposure of pre-differentiated SH-SY5Y cells to the Parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) resulted in significant dose-dependent reductions in TG2 protein levels, measured by probing Western blots with a TG2-specific antibody. Transglutaminase (TG) transamidating activity, on the other hand, monitored by incorporation of a polyamine pseudo-substrate into cellular proteins, was increased. Inhibitors of TG (putrescine) and TG2 (R283) exacerbated MPP+ toxicity, suggesting that activation of TG2 may promote a survival response in this toxicity paradigm.

The impact of buddying on psychological capital, work engagement and turnover intentions:an empirical study of socialization in the professional services sector

This article reports on a study investigating the impact of new employees' satisfaction with buddying on work engagement and explores the role of psychological capital in mediating this relationship. The study took place within a professional services organization wherein data were collected from 78 graduate newcomers in receipt of buddying. Satisfaction with buddying was found to have a positive relationship to both work engagement and psychological capital. The satisfaction with the buddy/work engagement relationship was fully mediated by psychological capital, providing support for Saks & Gruman's (2011) socialization resources theory. The results underscore the valuable role buddying can play as part of organizational socialization from a positive organizational behavior perspective. The research contributes to the growing evidence that positively oriented human resource practices can develop personal resources of newcomers within organizations. Recommendations are made for how the organization can improve and build upon this resource, thus developing the psychological capital of newcomers. © 2012 Wiley Periodicals, Inc.

Bone marrow-derived mesenchymal stem cells become anti-angiogenic when chondrogenically or osteogenically differentiated:implications for bone and cartilage tissue engineering

Osteochondral tissue repair requires formation of vascularized bone and avascular cartilage. Mesenchymal stem cells stimulate angiogenesis both in vitro and in vivo but it is not known if these proangiogenic properties change as a result of chondrogenic or osteogenic differentiation. We investigated the angiogenic/antiangiogenic properties of equine bone marrow-derived mesenchymal stem cells (eBMSCs) before and after differentiation in vitro. Conditioned media from chondrogenic and osteogenic cell pellets and undifferentiated cells was applied to endothelial tube formation assays using Matrigel™. Additionally, the cell secretome was analysed using LC-MS/MS mass spectrometry and screened for angiogenesis and neurogenesis-related factors using protein arrays. Endothelial tube-like formation was supported by conditioned media from undifferentiated eBMSCs. Conversely, chondrogenic and osteogenic conditioned media was antiangiogenic as shown by significantly decreased length of endothelial tube-like structures and degree of branching compared to controls. Undifferentiated cells produced higher levels of angiogenesis-related proteins compared to chondrogenic and osteogenic pellets. In summary, eBMSCs produce an array of angiogenesis-related proteins and support angiogenesis in vitro via a paracrine mechanism. However, when these cells are differentiated chondrogenically or osteogenically, they produce a soluble factor(s) that inhibits angiogenesis. With respect to osteochondral tissue engineering, this may be beneficial for avascular articular cartilage formation but unfavourable for bone formation where a vascularized tissue is desired. © Copyright 2014, Mary Ann Liebert, Inc.

The Role of Price Floor in a Differentiated Product Retail Market

The ability of a manufacturer to enhance competition among its retailers by imposing a price floor was recently introduced in the literature. The purpose of this article is to revisit this anti-collusive explanation of the retail price maintenance in a more general model in which we introduce asymmetric retailers. We find that a manufacturer can amplify the retail market’s competition by imposing a price foor when retailers sell differentiated products. This result contradicts the prevailing concept of retail price maintenance.

Exclusive contracts with vertically differentiated products

In this paper we develop a simple model to analyze the effects of exclusive contracts in vertically integrated markets where both the upstream and the downstream market are characterized as oligopolies and manufacturers produce vertically differentiated products. We find that firms prefer to deal exclusively with retailers. If the extent of consumers' heterogeneity is small, manufacturers offer exclusive contracts unilaterally. On the other hand, if consumers' valuations differ significantly both manufacturers engage in exclusive contracting.

Exclusive contracts with private information in successive differentiated oligopolies

The purpose of this article is to analyze the incentives of manufacturers to deal exclusively with retailers in bilaterally duopolistic industries with brand differentiation by manufacturers. In contrast with the previous literature, exclusive contracts are shown to generate higher profits for manufacturers and retailers selling highly differentiated products, who thus have an incentive to insist on exclusive contracting. However, if the products are close substitutes no exclusivity will emerge in equilibrium. Furthermore, we show that exclusive contracts decrease both consumer and social welfare.

The effects of cultural distance on student socialization and departure decisions

Organizational socialization theory and university student retention literature support the concept that social integration influences new recruits' level of satisfaction with the organization and their decision to remain. This three-phase study proposes and tests a Cultural Distance Model of student retention based on Tinto's (1975) Student Integration Model, Louis' (1980) Model of Newcomer Experience, and Kuh and Love's (2000) theory relating cultural distance to departure from the organization. ^ The main proposition tested in this study was that the greater the cultural distance, the greater the likelihood of early departure from the organization. Accordingly, it was inferred that new recruits entering the university culture experience some degree of social and psychological distance. The extent of the distance correspondingly influences satisfaction with the institution and intent to remain for subsequent years. ^ The model was tested through two freshman student surveys designed to examine the effects of cultural distance on non-Hispanics at a predominantly Hispanic, urban, public university. The first survey was administered eight weeks into their first Fall semester and the second at the end of their first year. Student retention was determined through their re-enrollment for the second Fall semester. Path analysis tested the viability of the hypothesis relating cultural distance to satisfaction and retention as suggested in the model. Logistic regression tested the model's predictive power. ^ Correlations among variables were significant, accounting for 54% of variance in students' decisions to return for the second year with 96% prediction accuracy. Initial feelings of high cultural distance were related to increased dissatisfaction with social interactions and institutional choice at the end of the first year and students' intention not to re-enroll. Path analysis results supported the view that the construct of culture distance incorporates both social and psychological distance, and is composed of beliefs of institutional fit with one's cultural expectations, individual comfort with the fit, and the consequent sense of “belonging” or identifying with the institution. ^