2,512 research outputs found

    Malaria vaccine research and development: the role of the WHO MALVAC committee.

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    The WHO Malaria Vaccine Advisory Committee (MALVAC) provides advice to WHO on strategic priorities, activities and technical issues related to global efforts to develop vaccines against malaria. MALVAC convened a series of meetings to obtain expert, impartial consensus views on the priorities and best practice for vaccine-related research and development strategies. The technical areas covered during these consultations included: guidance on clinical trial design for candidate sporozoite and asexual blood stage vaccines; measures of efficacy of malaria vaccines in Phase IIb and Phase III trials; standardization of immunoassays; the challenges of developing assays and designing trials for interventions against malaria transmission; modelling impact of anti-malarial interventions; whole organism malaria vaccines, and Plasmodium vivax vaccine-related research and evaluation. These informed discussions and opinions are summarized here to provide guidance on harmonization of strategies to help ensure high standards of practice and comparability between centres and the outcome of vaccine trials

    Long Distance Paths as Catalysts for Local Development: The Role of Parish Councils

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    Long distance paths are local resources, but previous research by the author suggested that they are not fully exploited by many rural communities. The continuing debate on rural governance following the publication of the Rural White Paper in November 2000, together with a curiosity as to the potential development role of parish councils resulted in the current research. This had three clear objectives. • What socio-cultural, environmental and economic benefits could be derived for local people from the presence of a long distance path? • Do parish councils assist in unlocking this potential, and if so, how? • Could this process be improved if parish councils acted differently? A two-phase research approach was adopted. Initially telephone interviews were used to conduct a broad based seeping study. This identified many relevant issues and provided introductions that led to the second phase when three case study locations were explored in greater depth. Here data was collected primarily through face-to-face semi structured interviews supplemented with documentary evidence. It was confirmed that there were minimal disbenefits but that the benefits were potentially considerable. At least half of the parish councils contributing to the research were found to participate in relevant local development to greater or lesser degrees. However it appears that not all parish councils are willing or able to accept responsibility for local development initiatives related to long distance paths. Some thought that local businesses or other agencies should promote and lead projects, whilst others were too busy dealing with routine matters. In addition parish councils were not always receptive to suggestions for collaborative working with other organisations. In all instances it was found that this local resource was not fully exploited by parish councils. Local authorities have more recently acknowledged the potential benefits brought by long distance paths. Thus during the last ten years new routes have been devised and it was found that parish councils were always consulted during the development phases, whilst historically the reason for, and the method of development of long distance routes was completely divorced from parish councils. In these latter instances parish councils needed to adopt a proactive approach to harness maximum community benefits. Generally however their activities were inhibited by several identified constraints. These were concerned with a lack of representation, skills and positive attitude towards local development initiatives. Examples of successful local development were identified that maximised endogenous resources and one of these is local people. It is suggested that if parish councils are to be successful the Government should first allocate sufficient resources for the capacity building of councillors and clerks which would enable them to take a more positive role in local development initiatives

    Effects of NaBu at different concentrations on the maturation rates of mouse GV stage oocytes.

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    Effects of NaBu at different concentrations on the maturation rates of mouse GV stage oocytes.</p

    Effect of age, GV transfer and modified nucleocytoplasmic ratio on PKCα in mouse oocytes and early embryos

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    SummaryProtein kinase C (PKC) is a family of Ser/Thr protein kinases that can be activated by Ca2+, phospholipid and diacylglycerol. There is evidence that PKC plays key roles in the meiotic maturation and activation of mammalian oocytes. The present study aimed to monitor the effect of age, germinal vesicle (GV) transfer and modified nucleoplasmic ratio on the subcellular distribution profile of PKCα, an important isozyme of PKC, in mouse oocytes undergoing meiotic maturation and following egg activation. Germinal vesicle oocytes were collected from 6–8-week-old and 12-month-old mice. Germinal vesicle-reconstructed oocytes and GV oocytes with one-half or one-third of the original oocyte volume were created using micromanipulation and electrofusion. The subcellular localization of PKCα was detected by immunocytochemistry and laser confocal microscopy. Our study showed that PKCα had a similar location pattern in oocytes and early embryos from young and old mice. PKCα was localized evenly in ooplasm, with weak staining in GV at the GV stage, and present in the entire meiosis II (MII) spindle at the MII stage. In pronuclear and 2-cell embryos, PKCα was concentrated in the nucleus except for the nucleolus. After the GV oocytes were reconstructed, the resultant MII oocytes and embryos showed a similar distribution of PKCα between reconstructed and unreconstructed controls. After one-half or two-thirds of the cytoplasm was removed from the GV oocytes, PKCα still had a similar location pattern in MII oocytes and early embryos from the GV oocytes with modified nucleoplasmic ratio. Our study showed that age, GV transfer and modified nucleocytoplasmic ratio does not affect distribution of PKCα during mouse oocyte maturation, activation, and early embryonic mitosis.</jats:p

    Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients.

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    Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality.Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve.4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813-0.834, P< 0.001) and 0.738 (95% CI: 0.725-0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001).We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group

    Correlation Between Blood Urea Nitrogen and Short- and Long-Term Glycemic Variability in Elderly Patients with Type 2 Diabetes Mellitus Who Were hospitalized:A Retrospective Study

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    Lining Huang,1 Zhaoxiang Wang,1 Ying Pan,1 Kaixin Zhou,2 Shao Zhong1 1Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China; 2Guangzhou Laboratory, Guangzhou, 510005, People’s Republic of ChinaCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email [email protected]: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and progressively impaired insulin secretion resulting in dynamic fluctuations in glucose levels.High blood urea nitrogen (BUN) levels have been linked to decreased insulin sensitivity, suppressed insulin synthesis and increased risk of incident diabetes mellitus in humans as well as insulin use in patients with T2DM.This study characterize the association between BUN levels and short-term and long-term glycemic variability(GV) in the elderly patients with T2DM who were hospitalized.Methods: A total of 927 elderly patients with T2DM were included in the study. The short-term GV was quantified using parameters such as standard deviation (SD), coefficient of variation (CV), time in range (TIR), and mean amplitude of glycemic excursions (MAGE), based on multi-point fingertip blood glucose monitoring. The long-term GV was quantified using parameters such as SD, CV, variation independent of the mean (VIM), and average successive variability (ARV), based on fasting blood glucose(FPG). The relationship between BUN levels and short-term and long-term GV in elderly T2DM who were hospitalized was explored using methods such as Spearman correlation coefficient, linear regression analysis, logistic regression analysis, and interaction tests.Results: In elderly patients with T2DM were hospitalized, there is a significant correlation between BUN levels and both short-term and long-term GV. BUN is negatively correlated with the GV parameter TIR (r=− 0.12, P=0.000), and positively correlated with SD (r=0.12, P=0.000), CV (r=0.07, P=0.026), MAGE (r=0.11, P=0.001), FPG-SD (r=0.08, P=0.013), and FPG-CV (r=0.08, P=0.014).Furthermore, the association remains consistent across different age, gender, BMI, and haemoglobin A1c (HbA1c) subgroups (P interaction > 0.05).Conclusion: In elderly patients with T2DM were hospitalized, BUN levels were positively associated with GV.Therefore, monitoring BUN levels were beneficial in assessing the degree of GV.Keywords: diabetes mellitus, glycemic variability, vascular lesions of diabetes mellitus, glycemic variability parameter

    Analysis of risk factors of long-term complications in congenital diaphragmatic hernia: A single institutions experience

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    To establish better management practices to reduce morbidities in survivors with congenital diaphragmatic hernia (CDH). Of 60 patients treated for CDH at our institution between 1991 and 2011, 49 patients without severe anomalies were retrospectively reviewed. Since 2004, gentle ventilation (GV) has been the main treatment for CDH. Patients were divided into the following two groups: the non-GV group (n = 29) who were treated before GV treatment was implemented, and the GV group (n = 20). The overall survival rate was 62.1% (18/29) and 95% (19/20) in the non-GV and GV groups, respectively (p = 0.016). Despite the high survival rate, the incidence of long-term complications in survivors was still high (14/19, 73.7%) in the GV group. In the GV group, liver-up (p = 0.106) and the need for patch repair (p = 0.257) tended to be associated with the development of long-term complications, but did not reach statistical significance. The presence of perioperative complications was associated with the development of long-term complications (p = 0.045) in the GV group. Patients who developed short-term complications seemed to be at risk of long-term complications. Therefore, to minimize long-term morbidities in CDH survivors, the prevention of short-term complications might be important

    Analysis of risk factors of long-term complications in congenital diaphragmatic hernia: A single institution's experience

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    SummaryObjectiveTo establish better management practices to reduce morbidities in survivors with congenital diaphragmatic hernia (CDH).MethodsOf 60 patients treated for CDH at our institution between 1991 and 2011, 49 patients without severe anomalies were retrospectively reviewed.ResultsSince 2004, gentle ventilation (GV) has been the main treatment for CDH. Patients were divided into the following two groups: the non-GV group (n = 29) who were treated before GV treatment was implemented, and the GV group (n = 20). The overall survival rate was 62.1% (18/29) and 95% (19/20) in the non-GV and GV groups, respectively (p = 0.016). Despite the high survival rate, the incidence of long-term complications in survivors was still high (14/19, 73.7%) in the GV group. In the GV group, liver-up (p = 0.106) and the need for patch repair (p = 0.257) tended to be associated with the development of long-term complications, but did not reach statistical significance. The presence of perioperative complications was associated with the development of long-term complications (p = 0.045) in the GV group.ConclusionPatients who developed short-term complications seemed to be at risk of long-term complications. Therefore, to minimize long-term morbidities in CDH survivors, the prevention of short-term complications might be important
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