Genetic variability in barley (Hordeum vulgare L.) landraces from Ethiopia as measured by morphological characters and SDS-page of seed storage proteins

Data on 44 barley landraces comprising collections and farmers’ cultivars from north Shewa, Ethiopia were studied for variability in morphological characters and Sodium Dodecyl Sulphate Polyacrylamide Gel Electophoresis (SDS-PAGE) of seed storage proteins. The phenotypic frequencies of morphological characters (qualitative and quantitative) were analysed by the Shanon Weaver diversity index (H’) to estimate within landrace genetic variability for individual characters. Variability for seed protein banding patterns was assessed by SDS-PAGE. Both morphological and SDS-PAGE data demonstrated the variability existing in the landraces. H’ values pooled over morphological characters ranged from 0.12 to 0.58. Among the qualitative characters, landraces showed higher levels of polymorphism for spike type than for kernel color, spike density and caryopsis type (covered or naked). Caryopsis type was the least diverse character observed. Diversity for quantitative characters pooled over landraces was generally very high especially for number of seeds spike-1 and days to maturity with respective H’ values of 0.90 and 0.98. DS-PAGE data based on representative lines from each landrace showed very low to high within landrace variability for banding patterns. Lines from landraces differed from each other in number and migration distances of bands. Some landraces that looked uniform for spike morphology also showed differences in banding patterns. It was also observed, on the other hand, that some landraces displaying different spike characters and hence assumed to exhibit differences of comparable magnitude in storage protein variability did not reveal much differences. Variability between landraces was higher than within landraces and variability within farmers’ cultivars was lower than within accessions. Clustering results of landraces from SDS-PAGE data were different in composition from those formed by morphological characters. Clustering from morphological data highlighted distinct grouping of landraces based on similarities in morphological characters whereas SDS-PAGE data did not depict such distinctness

Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data

Background Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP). Methods Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data. Results The systematic review identified 169 published and 9 unpublished studies, 126 of which were shared with the WorldWide Antimalarial Resistance Network (WWARN) and 121 trials including 48,840 patients were included in the analysis. Prevalence of gametocytaemia by microscopy at enrolment was 12.1 % (5887/48,589), and increased with decreasing age, decreasing asexual parasite density and decreasing haemoglobin concentration, and was higher in patients without fever at presentation. After ACT treatment, gametocytaemia appeared in 1.9 % (95 % CI, 1.7–2.1) of patients. The appearance of gametocytaemia was lowest after AS-MQ and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24–3.12; P = 0.005 compared to AL) and AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 2.40–6.72; P < 0.001 compared to AL). Among individuals who had gametocytaemia before treatment, gametocytaemia clearance was significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00–1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63–0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio (AOR), 9.05; 95 % CI, 3.74–21.90; P < 0.001) and new (AOR, 3.03; 95 % CI, 1.66–5.54; P < 0.001) infections with asexual-stage parasites were strongly associated with development of gametocytaemia after day 7. Conclusions AS-MQ and AL are more effective than DP and AS-AQ FDC in preventing gametocytaemia shortly after treatment, suggesting that the non-artemisinin partner drug or the timing of artemisinin dosing are important determinants of post-treatment gametocyte dynamics

Bending and Breaking of Stripes in a Charge-Ordered Manganite

In complex electronic materials, coupling between electrons and the atomic lattice gives rise to remarkable phenomena, including colossal magnetoresistance and metal-insulator transitions. Charge-ordered phases are a prototypical manifestation of charge-lattice coupling, in which the atomic lattice undergoes periodic lattice displacements (PLDs). Here we directly map the picometer scale PLDs at individual atomic columns in the room temperature charge-ordered manganite Bi$_{0.35}$Sr$_{0.18}$Ca$_{0.47}$MnO$_3$ using aberration corrected scanning transmission electron microscopy (STEM). We measure transverse, displacive lattice modulations of the cations, distinct from existing manganite charge-order models. We reveal locally unidirectional striped PLD domains as small as $\sim$5 nm, despite apparent bidirectionality over larger length scales. Further, we observe a direct link between disorder in one lattice modulation, in the form of dislocations and shear deformations, and nascent order in the perpendicular modulation. By examining the defects and symmetries of PLDs near the charge-ordering phase transition, we directly visualize the local competition underpinning spatial heterogeneity in a complex oxide.Comment: Main text: 20 pages, 4 figures. Supplemental Information: 27 pages, 14 figure

Commensurate Stripes and Phase Coherence in Manganites Revealed with Cryogenic Scanning Transmission Electron Microscopy

Incommensurate charge order in hole-doped oxides is intertwined with exotic phenomena such as colossal magnetoresistance, high-temperature superconductivity, and electronic nematicity. Here, we map at atomic resolution the nature of incommensurate order in a manganite using scanning transmission electron microscopy at room temperature and cryogenic temperature ($\sim$ 93K). In diffraction, the ordering wavevector changes upon cooling, a behavior typically associated with incommensurate order. However, using real space measurements, we discover that the underlying ordered state is lattice-commensurate at both temperatures. The cations undergo picometer-scale ($\sim$6-11 pm) transverse displacements, which suggests that charge-lattice coupling is strong and hence favors lattice-locked modulations. We further unearth phase inhomogeneity in the periodic lattice displacements at room temperature, and emergent phase coherence at 93K. Such local phase variations not only govern the long range correlations of the charge-ordered state, but also results in apparent shifts in the ordering wavevector. These atomically-resolved observations underscore the importance of lattice coupling and provide a microscopic explanation for putative "incommensurate" order in hole-doped oxides

The effect of dose on the antimalarial efficacy of artemether–lumefantrine: a systematic review and pooled analysis of individual patient data

Background Artemether–lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods We searched PubMed for clinical trials that enrolled and treated patients with artemether–lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. Findings We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4–97·9) at day 28 and 96·0% (95·6–96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86–0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10–15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5–96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1–3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3–96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85–0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation The recommended dose of artemether–lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data

Background Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5–64.9) on day 1 to 6.7 % (95 % CI: 4.8–8.7) on day 2 and 0.9 % (95 % CI: 0.5–1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08–1.25); per 2-fold increase in parasite density, P 37.5 °C) (AOR = 1.50 (95 % CI: 1.06–2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21–3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38–5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14–4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility

Assessing Livestock Water Productivity in Mixed Farming Systems of Gumara Watershed, Ethiopia

A monitoring study was carried out in Gumara watershed, upper Blue Nile basin, with the objective of evaluating livestock water productivity (LWP) using a life cycle assessment method. Sixty two smallholder farmers were selected for the study implemented between November 2006 and February 2008. Data on crop and livestock production were collected to allow assessment of livestock water productivity. Study sites were situated in three different rainfed mixed crop/livestock farming systems; barley/potato based system (BPS), tef/finger-millet based system (TMS), and rice/noug based system (RNS). LWP was found to be significantly lower (p < 0.01) in RNS (0.057 USD m−3 water) than in TMS (0.066 USD m−3 water) or in BPS (0.066 USD m−3 water). Notably, water requirement per kg live weight of cattle increased towards the lower altitude area (in RNS) mainly because of increased evapo-transpiration. As a result, 20% more water was required per kg live weight of cattle in the low ground RNS compared to BPS situated in the upstream parts of the study area. Cattle herd management that involved early offtake increased LWP by 28% over the practice of late offtake. Crop water productivity expressed in monetary units (0.39 USD m−3 water) was higher than LWP (0.063 USD m−3 water) across the mixed farming systems of Gumara watershed. Strategies for improving LWP, from its present low level, could include keeping only the more productive animals, increasing pasture productivity and linking production to marketing. These strategies would also ease the imbalance between the existing high livestock population and the declining carrying capacity of natural pasture.Peer Reviewe

Acute respiratory muscle unloading improves time-to-exhaustion during moderate- and heavy-intensity cycling in obese adolescent males

Obesity significantly impairs breathing during exercise. The aim was to determine, in male obese adolescents (OB), the effects of acute respiratory muscle unloading, obtained by switching the inspired gas from ambient air (AIR) to a normoxic helium + oxygen gas mixture (HeO2) (AIR \u2192 HeO2) during moderate [below gas exchange threshold (GET)] and heavy [above GET] constant work rate cycling. Ten OB [age 16.0 \ub1 2.0\ua0years (mean \ub1 SD); body mass index (BMI) 38.9 \ub1 6.1\ua0kg/m2] and ten normal-weight age-matched controls (CTRL) inspired AIR for the entire exercise task, or underwent AIR \u2192 HeO2 when they were approaching volitional exhaustion. In OB time to exhaustion (TTE) significantly increased in AIR \u2192 HeO2 vs. AIR during moderate [1524 \ub1 480\ua0s vs. 1308 \ub1 408 (P = 0.024)] and during heavy [570 \ub1 306\ua0s vs. 408 \ub1 150 (P = 0.0154)] exercise. During moderate exercise all CTRL completed the 40-min task. During heavy exercise no significant differences were observed in CTRL for TTE (582 \ub1 348\ua0s [AIR \u2192 HeO2] vs. 588 \ub1 252 [AIR]). In OB, but not in CTRL, acute unloading of respiratory muscles increased TTE during both moderate- and heavy-exercise. In OB, but not in CTRL, respiratory factors limit exercise tolerance during both moderate and heavy exercise

“Quality teaches you how to use water. It doesn’t provide a water pump”: a qualitative study of context and mechanisms of action in an Ethiopian quality improvement program

Background Quality improvement collaboratives are a common approach to bridging the quality-of-care gap, but little is known about implementation in low-income settings. Implementers rarely consider mechanisms of change or the role of context, which may explain collaboratives’ varied impacts. Methods To understand mechanisms and contextual influences we conducted 55 in-depth interviews with staff from four health centres and two hospitals involved in quality improvement collaboratives in Ethiopia. We also generated control charts for selected indicators to explore any impacts of the collaboratives. Results The cross facility learning sessions increased the prominence and focus on quality, allowed learning from experts and peers and were motivational through public recognition of success or a desire to emulate peers. Within facilities, new structures and processes were created. These were fragile and sometimes alienating to those outside the improvement team. The trusted and respected mentors were important for support, motivation and accountability. Where mentor visits were infrequent or mentors less skilled, team function was impacted. These mechanisms were more prominent, and quality improvement more functional, in facilities with strong leadership and pre-existing good teamwork; as staff had shared goals, an active approach to problems and were more willing and able to be flexible to implement change ideas. Quality improvement structures and processes were more likely to be internally driven and knowledge transferred to other staff in these facilities, which reduced the impact of staff turnover and increased buy-in. In facilities which lacked essential inputs, staff struggled to see how the collaborative could meaningfully improve quality and were less likely to have functioning quality improvement. The unexpected civil unrest in one region strongly disrupted the health system and the collaborative. These contextual issues were fluid, with multiple interactions and linkages. Conclusions The study confirms the need to carefully consider context in the implementation of quality improvement collaboratives. Facilities that implement quality improvement successfully may be those that already have characteristics that foster quality. Quality improvement may be alienating to those outside of the improvement team and implementers should not assume the organic spread or transfer of quality improvement knowledge