Iron Status and Associated Malaria Risk Among African Children.

BACKGROUND: It remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child's iron status influences their subsequent risk of malaria infection in sub-Saharan Africa. METHODS: We assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0-7 years and conducted prospective surveillance for episodes of malaria. Poisson regression models were fitted to determine the effect of iron status on the incidence rate ratio (IRR) of malaria using longitudinal data covering a period of 6 months. Models were adjusted for age, sex, parasitemia, inflammation, and study site. RESULTS: At baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. ID anemia (IDA) affected 23.6% of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with ID (IRR, 0.7; 95% confidence interval [CI], 0.6, 0.8; P < .001) and IDA (IRR, 0.7; 95% CI, 0.6, 0.9; P = .006). Low transferrin saturation (<10%) was similarly associated with lower malaria risk (IRR, 0.8; 95% CI, 0.6, 0.9; P = .016). However, variation in hepcidin, soluble transferrin receptors (sTfR), and hemoglobin/anemia was not associated with altered malaria risk. CONCLUSIONS: ID appears to protect against malaria infection in African children when defined using ferritin and transferrin saturation, but not when defined by hepcidin, sTfR, or hemoglobin. Additional research is required to determine causality. CLINICAL TRIALS REGISTRATION: ISRCTN32849447

Gravitino dark matter in the constrained next-to-minimal supersymmetric standard model with neutralino next-to-lightest superpartner

The viability of a possible cosmological scenario is investigated. The theoretical framework is the constrained next-to-minimal supersymmetric standard model (cNMSSM), with a gravitino playing the role of the lightest supersymmetric particle (LSP) and a neutralino acting as the next-to-lightest supersymmetric particle (NLSP). All the necessary constraints from colliders and cosmology have been taken into account. For gravitino we have considered the two usual production mechanisms, namely out-of equillibrium decay from the NLSP, and scattering processes from the thermal bath. The maximum allowed reheating temperature after inflation, as well as the maximum allowed gravitino mass are determined.Comment: 20 pages, 5 figure

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Direct neutralino searches in the NMSSM with gravitino LSP in the degenerate scenario

In the present work a two-component dark matter model is studied adopting the degenerate scenario in the R-parity conserving NMSSM. The gravitino LSP and the neutralino NLSP are extremely degenerate in mass, avoiding the BBN bounds and obtaining a high reheating temperature for thermal leptogenesis. In this model both gravitino (absolutely stable) and neutralino (quasi-stable) contribute to dark matter, and direct detection searches for neutralino are discussed. Points that survive all the constraints correspond to a singlino-like neutralino

An investigation into aripiprazole's partial D(2) agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory. Objectives: We probed the implications of the partial D2 receptor agonist actions of aripiprazole within the DLPFC during working memory. Investigations were carried out in healthy volunteers to eliminate confounds of illness or medication status. Aripiprazole’s prefrontal actions were compared with the D2/5-HT2A blocker risperidone to separate aripiprazole’s unique prefrontal D2 agonist actions from its serotinergic and striatal D2 actions that it shares with risperidone. Method: A double-blind, placebo-controlled, parallel design was implemented. Participants received a single dose of either 5 mg aripiprazole, 1 mg risperidone or placebo before performing the n-back task whilst undergoing fMRI scanning. Results: Compared with placebo, the aripiprazole group demonstrated enhanced DLPFC activation associated with a trend for improved discriminability (d’) and speeded reaction times. In contrast to aripiprazole’s neural effects, the risperidone group demonstrated a trend for reduced DLPFC recruitment. Unexpectedly, the risperidone group demonstrated similar effects to aripiprazole on d’ and additionally had reduced errors of commission compared with placebo. Conclusion: Aripiprazole has unique DLPFC actions attributed to its prefrontal D2 agonist action. Risperidone’s serotinergic action that results in prefrontal dopamine release may have protected against any impairing effects of its prefrontal D2 blockade

Iron status and associated malaria risk among African children

Background It remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child’s iron status influences their subsequent risk of malaria infection in sub-Saharan Africa. Methods We assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0 - 7 years and conducted prospective surveillance for episodes of malaria. Poisson regression models were fitted to determine the effect of iron status on the incidence rate ratio of malaria using longitudinal data covering a period of 6 months. Models were adjusted for age, sex, parasitemia, inflammation and study site. Results At baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. Iron deficiency anemia (IDA) affected 23.6% of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with ID (IRR = 0.7; 95% CI: 0.6, 0.8; p≺0.001) and IDA (IRR = 0.7; 95% CI: 0.6, 0.9; p=0.006). Low transferrin saturation (≺10%) was similarly associated with lower malaria risk (IRR = 0.8; 95% CI: 0.6, 0.9; p=0.016). However, variation in hepcidin, soluble transferrin receptors (sTfR) and hemoglobin / anemia was not associated with altered malaria risk. Conclusions ID appears to protect against malaria infection in African children when defined using ferritin and transferrin saturation, but not when defined by hepcidin, sTfR or hemoglobin. Further research is required to determine causality

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Estimating the burden of iron deficiency among African children.

BACKGROUND: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. METHODS: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8?years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin <?12??g/L or <?30??g/L in the presence of inflammation in children <?5?years old or <?15??g/L in children ??5?years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. RESULTS: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation <?11% most closely predicted the prevalence of ID according to the regression-correction gold standard. CONCLUSIONS: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa

Implementing the LifeSkills Training drug prevention program: factors related to implementation fidelity

<p>Abstract</p> <p>Background</p> <p>Widespread replication of effective prevention programs is unlikely to affect the incidence of adolescent delinquency, violent crime, and substance use until the quality of implementation of these programs by community-based organizations can be assured.</p> <p>Methods</p> <p>This paper presents the results of a process evaluation employing qualitative and quantitative methods to assess the extent to which 432 schools in 105 sites implemented the LifeSkills Training (LST) drug prevention program with fidelity. Regression analysis was used to examine factors influencing four dimensions of fidelity: adherence, dosage, quality of delivery, and student responsiveness.</p> <p>Results</p> <p>Although most sites faced common barriers, such as finding room in the school schedule for the program, gaining full support from key participants (i.e., site coordinators, principals, and LST teachers), ensuring teacher participation in training workshops, and classroom management difficulties, most schools involved in the project implemented LST with very high levels of fidelity. Across sites, 86% of program objectives and activities required in the three-year curriculum were delivered to students. Moreover, teachers were observed using all four recommended teaching practices, and 71% of instructors taught all the required LST lessons. Multivariate analyses found that highly rated LST program characteristics and better student behavior were significantly related to a greater proportion of material taught by teachers (adherence). Instructors who rated the LST program characteristics as ideal were more likely to teach all lessons (dosage). Student behavior and use of interactive teaching techniques (quality of delivery) were positively related. No variables were related to student participation (student responsiveness).</p> <p>Conclusion</p> <p>Although difficult, high implementation fidelity by community-based organizations can be achieved. This study suggests some important factors that organizations should consider to ensure fidelity, such as selecting programs with features that minimize complexity while maximizing flexibility. Time constraints in the classroom should be considered when choosing a program. Student behavior also influences program delivery, so schools should train teachers in the use of classroom management skills. This project involved comprehensive program monitoring and technical assistance that likely facilitated the identification and resolution of problems and contributed to the overall high quality of implementation. Schools should recognize the importance of training and technical assistance to ensure quality program delivery.</p