Innovative approaches through mobile apps to improve tenure security in subSaharan Africa

Due to the affordances of new digital data technologies in conjunction with policy paradigms of efficiency, participation, transparency, and open government, innovative tools and approaches for tenure documentation have emerged in recent years. This brief paper discusses these apps/tools and experiences in implementation within their respective contexts

Medication education program for Indian children with asthma: A feasibility study

Objective: It is postulated that children with asthma who receive an interactive, comprehensive,  culturally relevant education program would improve their asthma knowledge (AK), asthma control, and adherence compared with children receiving usual care. The aim of this study was to develop, implement, and evaluate the efficacy of a culturally relevant asthma education intervention for children with asthma and their parents in India.Methods: Children with asthma (7.12 years) and their parents were recruited from an outpatient clinic in a Chest Diseases Hospital in New Delhi, and were randomly assigned to either an intervention or usual care group. At baseline, outcome data collected included pediatric asthma caregiver quality of life (PACQL, primary outcome), AK, asthma control, adherence, inhaler technique, action plan ownership, and goal achievement. These data were collected again at 1 and 6 months after baseline. Outcomes were compared within and between groups using ANOVA techniques.Results: Forty parent.child pairs were recruited. Of these, 24 pairs of children with asthma and their parents received the educational intervention. The PACQL significantly improved from baseline to 6 months in the intervention (5.87 } 0.94.7.00 } 0.03) versus the usual care group (5.90 } 0.52.6.34 } 0.56) (P < 0.001). Other outcomes such as the parentsf and childfs AK, childfs asthma control and inhaler technique were significantly improved in the intervention group across the study. All the participants possessed a written asthma action plan at the end of the intervention. Eighty.five goals were set by children with asthma across all the visits and were achieved by completion.Conclusion: An asthma educator delivered interactive program simultaneously involving children with asthma and their parents, improved quality of life, empowered and promoted better self.management skills.Key words: Asthma education, asthma knowledge, asthma usual care, caregiver quality of life, childhood asthma, hospital.based program, program evaluatio

A family history of breast cancer will not predict female early onset breast cancer in a population-based setting

ABSTRACT: BACKGROUND: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting. METHODS: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer. RESULTS: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30. CONCLUSION: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age

Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes

© 2017 The Authors Human astrocytes network with neurons in dynamic ways that are still poorly defined. Our ability to model this relationship is hampered by the lack of relevant and convenient tools to recapitulate this complex interaction. To address this barrier, we have devised efficient coculture systems utilizing 3D organoid-like spheres, termed asteroids, containing pre-differentiated human pluripotent stem cell (hPSC)-derived astrocytes (hAstros) combined with neurons generated from hPSC-derived neural stem cells (hNeurons) or directly induced via Neurogenin 2 overexpression (iNeurons). Our systematic methods rapidly produce structurally complex hAstros and synapses in high-density coculture with iNeurons in precise numbers, allowing for improved studies of neural circuit function, disease modeling, and drug screening. We conclude that these bioengineered neural circuit model systems are reliable and scalable tools to accurately study aspects of human astrocyte-neuron functional properties while being easily accessible for cell-type-specific manipulations and observations. In this article, Krencik and colleagues show that high-density cocultures of pre-differentiated human astrocytes with induced neurons, from pluripotent stem cells, elicit mature characteristics by 3–5 weeks. This provides a faster and more defined alternative method to organoid cultures for investigating human neural circuit function.This work has been supported by the Paul G. Allen Family Foundation Award, SFARI Award 345471, NIMH ( R01MH099595-01 ), That Man May See, NIH-NEI ( EY002162 ) Core Grant for Vision Research, and the Research to Prevent Blindness Unrestricted Grant

Increased accumulation of doxorubicin and doxorubicinol in cardiac tissue of mice lacking mdr1a P-glycoprotein

To gain more insight into the pharmacological role of endogenous P-glycoprotein in the metabolism of the widely used substrate drug doxorubicin, we have studied the plasma pharmacokinetics, tissue distribution and excretion of this compound in mdr1a(–/– and wild-type mice. Doxorubicin was administered as an i.v. bolus injection at a dose level of 5 mg kg−1. Drug and metabolite concentrations were determined in plasma, tissues, urine and faeces by high-performance liquid chromatography. In comparison with wild-type mice, the terminal half-life and the area under the plasma concentration–time curve of doxorubicin in it>mdr1a(–/–) mice were 1.6- and 1.2-fold higher respectively.The retention of both doxorubicin and its metabolite doxorubicinol in the hearts of mdr1a(–/–) mice was substantially prolonged. In addition, a significantly increased drug accumulation was observed in the brain and the liver of mdr1a(–/–) mice. The relative accumulation in most other tissues was not or only slightly increased. The differences in cumulative faecal and urinary excretion of doxorubicin and metabolites between both types of mice were small. These experiments demonstrate that the absence of mdr1a P-glycoprotein only slightly alters the plasma pharmacokinetics of oxorubicin. Furthermore, the substantially prolonged presence of both doxorubicin and doxorubicinol in cardiac tissue of mdr1a(–/–) mice suggests that a blockade of endogenous P-glycoprotein in patients, for example by a reversal agent, may enhance the risk of cardiotoxicity upon administration of doxorubicin. © 1999 Cancer Research Campaig

Paediatric Acute Respiratory Distress Syndrome Neuromuscular Blockade study (PAN-study):a phase IV randomised controlled trial of early neuromuscular blockade in moderate-to-severe paediatric acute respiratory distress syndrome

BACKGROUND: Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40–50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU). METHODS: This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H(2)O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS. TRIAL REGISTRATION: ClinicalTrials.govNCT02902055. Registered on September 15, 2016

Sequential biomolecular, macrofossil, and microfossil extraction from coprolites for reconstructing past behavior and environments

The study of macroscopic, microscopic, and biomolecular remains recovered from coprolites can provide a wide range of information on past human and animal behavior and environments. In earlier studies, research tended to focus on one or two proxies, but multiproxy approaches combining data from all remains within coprolites are becoming more common. Multiproxy analyses have demonstrated value for strengthening our understanding of the past and reducing equifinality. Here we present a sequential biomolecular, macrofossil, and microfossil extraction protocol that separates all different coprolite components and is intended as a best-practice guideline for coprolite analysis. We demonstrate the effectiveness of this method by applying it to an assemblage of coprolites from the Paisley Caves, Oregon, USA. By combining a wide range of proxies, this study provides important information on the taxonomy and behavior of organisms in the past as well as the paleoecological context of behavior

The role of termite CH4 emissions on the ecosystem scale: a case study in the Amazon rainforest.

The magnitude of termite methane (CH4) emissions is still an uncertain part of the global CH4 budget and current emission estimates are based on limited field studies. We present in situ CH4 emission measurements of termite mounds and termite mound subsamples performed in the Amazon rainforest. Emissions from five termite mounds of the species Neocapritermes brasiliensis were measured by use of a large flux chamber connected to a portable gas analyser measuring CH4 and CO2. In addition, the emissions of mound subsamples were measured, after which the termites were counted so that a termite CH4 and CO2 emission factor could be determined. Mound emissions were found to range between 17.0 and for CH4 and between 1.1 and for CO2. A termite emission factor of was found, which is almost twice as high as the only other reported value for the Amazon. By combining mound emission measurements with the termite emission factor, colony sizes could be estimated, which were found to range between 55?125 thousand individuals. Estimates were similar to literature values, and we therefore propose that this method can be used as a quick non-intrusive method to estimate termite colony size in the field. The role of termites in the ecosystem's CH4 budget was evaluated by use of two approaches. Termite mound emission values were combined with local mound density numbers, leading to an estimate of , on average, emitted by termite mounds. In addition, the termite CH4 emission factor from this study was combined with termite biomass numbers, resulting in an estimate of termite-emitted CH4 of . Considering the relatively low net CH4 emissions previously measured at this ecosystem, we expect that termites play an important role in the CH4 budget of this terra firme ecosystem

A simple method for co-segregation analysis to evaluate the pathogenicity of unclassified variants; BRCA1 and BRCA2 as an example

BACKGROUND: Assessment of the clinical significance of unclassified variants (UVs) identified in BRCA1 and BRCA2 is very important for genetic counselling. The analysis of co-segregation of the variant with the disease in families is a powerful tool for the classification of these variants. Statistical methods have been described in literature but these methods are not always easy to apply in a diagnostic setting. METHODS: We have developed an easy to use method which calculates the likelihood ratio (LR) of an UV being deleterious, with penetrance as a function of age of onset, thereby avoiding the use of liability classes. The application of this algorithm is publicly available http://www.msbi.nl/cosegregation. It can easily be used in a diagnostic setting since it requires only information on gender, genotype, present age and/or age of onset for breast and/or ovarian cancer. RESULTS: We have used the algorithm to calculate the likelihood ratio in favour of causality for 3 UVs in BRCA1 (p.M18T, p.S1655F and p.R1699Q) and 5 in BRCA2 (p.E462G p.Y2660D, p.R2784Q, p.R3052W and p.R3052Q). Likelihood ratios varied from 0.097 (BRCA2, p.E462G) to 230.69 (BRCA2, p.Y2660D). Typing distantly related individuals with extreme phenotypes (i.e. very early onset cancer or old healthy individuals) are most informative and give the strongest likelihood ratios for or against causality. CONCLUSION: Although co-segregation analysis on itself is in most cases insufficient to prove pathogenicity of an UV, this method simplifies the use of co-segregation as one of the key features in a multifactorial approach considerably