Operational Issues and Trends Associated with the Pilot Introduction of Zinc for Childhood Diarrhoea in Bougouni District, Mali

Zinc for the treatment of childhood diarrhoea was introduced in a pilot area in southern Mali to prepare for a cluster-randomized effectiveness study and to inform policies on how to best introduce and promote zinc at the community level. Dispersible zinc tablets in 14-tablet blister packs were provided through community health centres and drug kits managed by community health workers (CHWs) in two health zones in Bougouni district, Mali. Village meetings and individual counselling provided by CHWs and head nurses at health centres were the principal channels of communication. A combination of methods were employed to (a) detect problems in communication about the benefits of zinc and its mode of administration; (b) identify and resolve obstacles to implementation of zinc through existing health services; and (c) describe household-level constraints to the adoption of appropriate home-management practices for diarrhoea, including administration of both zinc and oral rehydration solution (ORS). Population-based household surveys with caretakers of children sick in the previous two weeks were carried out before and four months after the introduction of zinc supplementation. Household follow-up visits with children receiving zinc from the health centres and CHWs were conducted on day 3 and 14 after treatment for a subsample of children. A qualitative process evaluation also was conducted to investigate operational issues. Preliminary evidence from this study suggests that the introduction of zinc does not reduce the use of ORS and may reduce inappropriate antibiotic use for childhood diarrhoea. Financial access to treatments, management of concurrent diarrhoea and fever, and high use of unauthorized drug vendors were identified as factors affecting the effectiveness of the intervention in this setting. The introduction of zinc, if not appropriately integrated with other disease-control strategies, has the potential to decrease the appropriate presumptive treatment of childhood malaria in children with diarrhoea and fever in malaria-endemic areas

Examining the association of life course neurocognitive ability with real-world functioning in schizophrenia-spectrum disorders

There is considerable variability in neurocognitive functioning within schizophrenia-spectrum disorders, and neurocognitive performance ranges from severe global impairment to normative performance. Few investigations of neurocognitive clusters have considered the degree to which deterioration relative to premorbid neurocognitive abilities is related to key illness characteristics. Moreover, while neurocognition and community functioning are strongly related, understanding of the sources of variability in the association between these two domains is also limited; it is unknown what proportion of participants would over-perform or under-perform the level of functioning expected based on current neurocognitive performance vs. lifelong attainment. This study examined data from 954 outpatients with schizophrenia-spectrum disorders across three previous studies. Neurocognition, community functioning, and symptoms were assessed. Neurocognitive subgroups were created based on current neurocognition, estimated premorbid IQ, and degree of deterioration from premorbid using z-score cut-offs; functional subgroups were created with cluster analysis based on the Specific Level of Functioning Scale and current neurocognition. The sample was neurocognitively heterogeneous; 65% displayed current neurocognitive impairment and 84% experienced some level of deterioration. Thirty percent of our sample was relatively higher functioning despite significant neurocognitive impairment. Individuals with better community functioning, regardless of neurocognitive performance, had lower symptom severity compared to those with worse functioning. These results highlight the variability in neurocognition and its role in functioning. Understanding individual differences in neurocognitive and functional profiles and the interaction between prior and current cognitive functioning can guide individualized treatment and selection of participants for clinical treatment studies

The telomere of human chromosome 1p contains at least two independent autosomal dominant congenital cataract genes.

AIMS: Multiple genetic causes of congenital cataract have been identified, both as a component of syndromes and in families that present with isolated congenital cataract. Linkage analysis was used to map the genetic locus in a six generation Australian family presenting with total congenital cataract. METHODS: Microsatellite markers located across all known autosomal dominant congenital cataract loci were genotyped in all recruited family members of the Tasmanian family. Both two point and multipoint linkage analysis were used to assess each locus under an autosomal dominant model. RESULTS: Significant linkage was detected at the telomere of the p arm of chromosome 1, with a maximum two point LOD of 4.21 at marker D1S507, a maximum multipoint exact LOD of 5.44, and an estimated location score of 5.61 at marker D1S507. Haplotype analysis places the gene inside a critical region between D1S228 and D1S199, a distance of approximately 6 megabases. The candidate gene PAX7 residing within the critical interval was excluded by direct sequencing in affected individuals. CONCLUSION: This is the third report of congenital cataract linkage to 1ptel. The critical region as defined by the shared haplotype in this family is clearly centromeric from the Volkmann cataract locus identified through study of a Danish family, indicating that two genes causing autosomal dominant congenital cataract map to the telomeric region of chromosome 1p

Factors associated with mosquito net use by individuals in households owning nets in Ethiopia

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Ownership of insecticidal mosquito nets has dramatically increased in Ethiopia since 2006, but the proportion of persons with access to such nets who use them has declined. It is important to understand individual level net use factors in the context of the home to modify programmes so as to maximize net use. Methods Generalized linear latent and mixed models (GLLAMM) were used to investigate net use using individual level data from people living in net-owning households from two surveys in Ethiopia: baseline 2006 included 12,678 individuals from 2,468 households and a sub-sample of the Malaria Indicator Survey (MIS) in 2007 included 14,663 individuals from 3,353 households. Individual factors (age, sex, pregnancy); net factors (condition, age, net density); household factors (number of rooms [2006] or sleeping spaces [2007], IRS, women's knowledge and school attendance [2007 only], wealth, altitude); and cluster level factors (rural or urban) were investigated in univariate and multi-variable models for each survey. Results In 2006, increased net use was associated with: age 25-49 years (adjusted (a) OR = 1.4, 95% confidence interval (CI) 1.2-1.7) compared to children U5; female gender (aOR = 1.4; 95% CI 1.2-1.5); fewer nets with holes (Ptrend = 0.002); and increasing net density (Ptrend < 0.001). Reduced net use was associated with: age 5-24 years (aOR = 0.2; 95% CI 0.2-0.3). In 2007, increased net use was associated with: female gender (aOR = 1.3; 95% CI 1.1-1.6); fewer nets with holes (aOR [all nets in HH good] = 1.6; 95% CI 1.2-2.1); increasing net density (Ptrend < 0.001); increased women's malaria knowledge (Ptrend < 0.001); and urban clusters (aOR = 2.5; 95% CI 1.5-4.1). Reduced net use was associated with: age 5-24 years (aOR = 0.3; 95% CI 0.2-0.4); number of sleeping spaces (aOR [per additional space] = 0.6, 95% CI 0.5-0.7); more old nets (aOR [all nets in HH older than 12 months] = 0.5; 95% CI 0.3-0.7); and increasing household altitude (Ptrend < 0.001). Conclusion In both surveys, net use was more likely by women, if nets had fewer holes and were at higher net per person density within households. School-age children and young adults were much less likely to use a net. Increasing availability of nets within households (i.e. increasing net density), and improving net condition while focusing on education and promotion of net use, especially in school-age children and young adults in rural areas, are crucial areas for intervention to ensure maximum net use and consequent reduction of malaria transmission.Peer Reviewe

A method for successful collection of multicores and gravity cores from Antarctic subglacial lakes

During the 2018–2019 Antarctic field season, the Subglacial Antarctic Lakes Scientific Access project team cleanly accessed Mercer Subglacial Lake, West Antarctica, to sample water and sediments beneath 1087 m of overlying ice. A multicorer was successful in sampling the sediment–water interface, with 4 deployments retrieving 10 cores between 0.3 and 0.4 m in length. Gravity coring was also successful, retrieving cores of 0.97 and 1.78 m in glacial diamict. However, sediment cores retrieved by the gravity cores were shorter than the core barrel penetration (as measured by mud streaks on the outside of the coring system), indicating that the system can likely be improved. This manuscript describes the design, implementation, successes, and lessons learned while coring sediments in a subglacial lake

Operational Issues and Trends Associated with the Pilot Introduction of Zinc for Childhood Diarrhoea in Bougouni District, Mali

Zinc for the treatment of childhood diarrhoea was introduced in a pilot area in southern Mali to prepare for a cluster-randomized effectiveness study and to inform policies on how to best introduce and promote zinc at the community level. Dispersible zinc tablets in 14-tablet blister packs were provided through community health centres and drug kits managed by community health workers (CHWs) in two health zones in Bougouni district, Mali. Village meetings and individual counselling provided by CHWs and head nurses at health centres were the principal channels of communication. A combination of methods were employed to (a) detect problems in communication about the benefits of zinc and its mode of administration; (b) identify and resolve obstacles to implementation of zinc through existing health services; and (c) describe household-level constraints to the adoption of appropriate home-management practices for diarrhoea, including administration of both zinc and oral rehydration solution (ORS). Population-based household surveys with caretakers of children sick in the previous two weeks were carried out before and four months after the introduction of zinc supplementation. Household follow-up visits with children receiving zinc from the health centres and CHWs were conducted on day 3 and 14 after treatment for a subsample of children. A qualitative process evaluation also was conducted to investigate operational issues. Preliminary evidence from this study suggests that the introduction of zinc does not reduce the use of ORS and may reduce inappropriate antibiotic use for childhood diarrhoea. Financial access to treatments, management of concurrent diarrhoea and fever, and high use of unauthorized drug vendors were identified as factors affecting the effectiveness of the intervention in this setting. The introduction of zinc, if not appropriately integrated with other disease-control strategies, has the potential to decrease the appropriate presumptive treatment of childhood malaria in children with diarrhoea and fever in malaria-endemic areas

Getting It Right: Being Smarter about Clinical Trials

A major NIH meeting led to recommendations for conducting better clinical trials

Hyperpolarized 13C-MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer

Purpose: To compare hyperpolarized carbon-13 (13C)-MRI with dynamic contrast-enhanced MRI (DCE-MRI) for detecting early treatment response in breast cancer. Materials and Methods: In this institutional review board-approved prospective study, one woman with triple-negative breast cancer (age 49) underwent 13C-MRI following injection of hyperpolarized [1-13C]pyruvate and DCE-MRI at 3 T at baseline and after a single cycle of neoadjuvant therapy. The 13C-lactate/13C-pyruvate ratio derived from hyperpolarized 13C-MRI and the pharmacokinetic parameters Ktrans and kep derived from DCE-MRI were compared, before and after treatment. Results: Exchange of the 13C-label between injected hyperpolarized [1-13C]pyruvate and the endogenous lactate pool was demonstrated, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the 13C-lactate/13C-pyruvate ratio was shown to correctly identify the patient as a responder to therapy, which was subsequently confirmed by a complete pathologic response. However, DCE-MRI showed an increase in the pharmacokinetic parameters Ktrans (132%) and kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized 13C-MRI successfully identified response in breast cancer after a single cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI.This work was supported by a Wellcome Trust Strategic Award, Cancer Research UK (CRUK; Grants C8742/A18097, C19212/ A16628, C19212/A911376, and C197/A16465), the Austrian Science Fund (Grant J4025-B26), the CRUK Cambridge Centre, the CRUK & Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, the Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre (Grant C9685/A25177), CRUK National Cancer Imaging Translational Accelerator Award, Addenbrooke’s Charitable Trust, the National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, and Cambridge University Hospitals National Health Service Foundation Trust

Imaging breast cancer using hyperpolarized carbon-13 MRI.

Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia