Assessing doctors' competencies using multisource feedback: validating a Japanese version of the Sheffield Peer Review Assessment Tool (SPRAT).

OBJECTIVE: To assess the validity and reliability of the Sheffield Peer Review Assessment Tool (SPRAT) Japanese version for evaluating doctors' competencies using multisource feedback. METHODS: SPRAT, originally developed in the UK, was translated and validated in three phases: (1) an existing Japanese version of SPRAT was back-translated into English; (2) two expert panel meetings were held to develop and assure content validity in a Japanese setting; (3) the newly devised Japanese SPRAT instrument was tested by a multisource feedback survey, validity was tested using principal component factor analysis, and reliability was assessed using generalisability and decision studies based on generalisability theory. RESULTS: 86 doctors who had been practising for between 2 and 33 years participated as assessees and were evaluated with the SPRAT tool. First, the doctors identified 1019 potential assessors who were each sent SPRAT forms (response rate, 81%). The mean number of assessors per doctor was 9.7 (SD=2.5). The decision study showed that 95% CIs of ± 0.5 were achieved with only 5 assessors. 85 of the 86 doctors achieved scores that could be placed with 95% CI above the 4 expected standard. Doctors received lower scores from more senior assessors (p<0.001) and higher scores from those they had known longer (p<0.001). Scores also varied with the job role (p<0.05). CONCLUSIONS: Following translation and content validation, the Japanese instrument behaved similarly to the UK tool. Assessor selection remains a primary concern, as the assessment scores are affected by the seniority of the assessor, the length of the assessor-assessee working relationship, and the assessor's job role. Users of the SPRAT tool need to be aware of these limitations when administering the instrument

Long-Term Effects of Polychlorinated Biphenyls and Dioxins on Pregnancy Outcomes in Women Affected by the Yusho Incident

Background: Maternal exposure to polychlorinated biphenyls (PCBs) is associated with increased proportions of spontaneous abortion and stillbirth in animal studies. In Japan in 1968, accidental human exposure to rice oil contaminated with PCBs and other dioxin-related compounds, such as polychlorinated dibenzofurans (PCDFs), led to the development of what was later referred to as Yusho oil disease. Objective: The aim of this study was to investigated the association of maternal PCB and dioxin exposure with adverse pregnancy outcomes in Yusho women. Methods: In 2004, we interviewed 214 Yusho women (512 pregnancies) about their pregnancy outcomes over the past 36 years. Pregnancy outcomes included induced abortion, spontaneous abortion, preterm delivery, and pregnancy loss. Results: In pregnancy years 1968-1977 (within the first 10 years after exposure), the proportions of induced abortion [adds ration adjusted for age at delivery (ORadj) = 5.93; 95% confidence interval (CI), 2.21-15.91; two-tailed p < 0.001) and preterm delivery (ORadj = 5.70; 95% CI, 1.17-27.79; p = 0.03) were significantly increased compared with the proportions in pregnancy years 1958-1967 (10 years before the incident). Spontaneous abortion (ORadj = 2.09; 95% CI, 0.84-5.18), and pregnancy loss (ORadj = 2.11; 95% CI, 0.92-4.87) were more frequent (OR = 2.18; 95% CI, 1.02-4.66), but these were not significant (p = 0.11 and p = 0.08, respectively) in pregnancy years 1968-1977. We found no significant increases in the proportions of these adverse pregnancy outcomes in pregnancies occurring during 1978-1987 or 1988-2003 compared with those in pregnancies before 1968. Conclusion: High levels of PCB/PCDF exposure had some adverse effects on pregnancy outcome in Yusho women

Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: An International Study

BACKGROUND Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable

Integração da simulação termoenergética nas primeiras fases do processo projetual: o estudo de seis casos

Resumo O artigo tem o objetivo de demonstrar a viabilidade de integração de simulações termoenergéticas ao processo projetual desde as primeiras fases do projeto. Para tanto, apresenta uma sistematização dos procedimentos entre projetista e simulador para seis estudos de caso de edificações em clima quente. Destaca-se a necessidade de compreensão das características do edifício e da programação arquitetônica, incluindo informações, metas e necessidade, além de partido e intenções da solução, que motivaram a montagem de um checklist para melhorar o diálogo entre simulador e projetista. Os resultados também apontam as características da edificação que mais influenciam no consumo energético da edificação, e a interação entre o simulador e o projetista, de acordo com seu perfil, as liberdades e restrições implícitas, e a recorrência das soluções, que poderiam até mesmo dispensar as simulações. Além da confirmação de que é possível integrar simulações desde as primeiras fases, a contribuição principal do artigo é o mapeamento de processos entre projetista e simulador e sua intensidade para demonstrar as potencialidades e limitações das integrações, que podem ser úteis no desenvolvimento de interfaces de ferramentas e no treinamento de especialistas em simulação

Efficient and Directive Generation of Two Distinct Endoderm Lineages from Human ESCs and iPSCs by Differentiation Stage-Specific SOX17 Transduction

The establishment of methods for directive differentiation from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is important for regenerative medicine. Although Sry-related HMG box 17 (SOX17) overexpression in ESCs leads to differentiation of either extraembryonic or definitive endoderm cells, respectively, the mechanism of these distinct results remains unknown. Therefore, we utilized a transient adenovirus vector-mediated overexpression system to mimic the SOX17 expression pattern of embryogenesis. The number of alpha-fetoprotein-positive extraembryonic endoderm (ExEn) cells was increased by transient SOX17 transduction in human ESC- and iPSC-derived primitive endoderm cells. In contrast, the number of hematopoietically expressed homeobox (HEX)-positive definitive endoderm (DE) cells, which correspond to the anterior DE in vivo, was increased by transient adenovirus vector-mediated SOX17 expression in human ESC- and iPSC-derived mesendoderm cells. Moreover, hepatocyte-like cells were efficiently generated by sequential transduction of SOX17 and HEX. Our findings show that a stage-specific transduction of SOX17 in the primitive endoderm or mesendoderm promotes directive ExEn or DE differentiation by SOX17 transduction, respectively

Outer Membrane Vesicles as a Candidate Vaccine against Edwardsiellosis

Infection with Edwardsiella tarda, a Gram-negative bacterium, causes high morbidity and mortality in both marine and freshwater fish. Outer membrane vesicles (OMVs) released from Gram-negative bacteria are known to play important roles in bacterial pathogenesis and host immune responses, but no such roles for E. tarda OMVs have yet been described. In the present study, we investigated the proteomic composition of OMVs and the immunostimulatory effect of OMVs in a natural host, as well as the efficacy of OMVs when used as a vaccine against E. tarda infection. A total of 74 proteins, from diverse subcellular fractions, were identified in OMVs. These included a variety of important virulence factors, such as hemolysin, OmpA, porin, GAPDH, EseB, EseC, EseD, EvpC, EvpP, lipoprotein, flagellin, and fimbrial protein. When OMVs were administrated to olive flounder, significant induction of mRNAs encoding IL-1β, IL-6, TNFα, and IFNγ was observed, compared with the levels seen in fish injected with formalin-killed E. tarda. In a vaccine trial, olive flounder given OMVs were more effectively protected (p<0.0001) than were control fish. Investigation of OMVs may be useful not only for understanding the pathogenesis of E. tarda but also in development of an effective vaccine against edwardsiellosis

Ex Vivo Expansion of Human CD8+ T Cells Using Autologous CD4+ T Cell Help

Background: Using in vivo mouse models, the mechanisms of CD4+ T cell help have been intensively investigated. However, a mechanistic analysis of human CD4+ T cell help is largely lacking. Our goal was to elucidate the mechanisms of human CD4+ T cell help of CD8+ T cell proliferation using a novel in vitro model. Methods/Principal Findings: We developed a genetically engineered novel human cell-based artificial APC, aAPC/mOKT3, which expresses a membranous form of the anti-CD3 monoclonal antibody OKT3 as well as other immune accessory molecules. Without requiring the addition of allogeneic feeder cells, aAPC/mOKT3 enabled the expansion of both peripheral and tumor-infiltrating T cells, regardless of HLA-restriction. Stimulation with aAPC/mOKT3 did not expand Foxp3+ regulatory T cells, and expanded tumor infiltrating lymphocytes predominantly secreted Th1-type cytokines, interferon-γ and IL-2. In this aAPC-based system, the presence of autologous CD4+ T cells was associated with significantly improved CD8+ T cell expansion in vitro. The CD4+ T cell derived cytokines IL-2 and IL-21 were necessary but not sufficient for this effect. However, CD4+ T cell help of CD8+ T cell proliferation was partially recapitulated by both adding IL-2/IL-21 and by upregulation of IL-21 receptor on CD8+ T cells. Conclusions: We have developed an in vitro model that advances our understanding of the immunobiology of human CD4+ T cell help of CD8+ T cells. Our data suggests that human CD4+ T cell help can be leveraged to expand CD8+ T cells in vitro