Successes and challenges of the millennium development goals in Ethiopia: lessons for the sustainable development goals

We analysed the performance of Ethiopia in achieving the health-related millennium development goals (MDGs) with the aim of acquiring lessons for the sustainable development goals (SDGs). Ethiopia achieved most of the health MDGs: a 67% reduction in under-five mortality, a 71% decline in maternal mortality ratio, a 90% decline in new HIV infections, a decrease in malaria-related deaths by 73% and a more than 50% decline in mortality due to tuberculosis. We argue that these achievements are due to implementation of a mix of comprehensive strategies within the health system and across other sectors of the government. Scaling up of interventions by disease control programmes (including the health extension programme) and strengthening of the health system have played important roles towards the achievements. These health gains could not have been realised without progress in the other MDGs: poverty reduction, education, access to safe drinking-water and peace and stability of the country. However, the gains were not equitable, with differences between urban and rural areas, among regions and socioeconomic strata. Ethiopia's remarkable success in meeting most of the targets of the health-related MDGs could be explained by its comprehensive and multisectoral approach for health development. The inequity gap remains a challenge that achieving the health-related SDGs requires the country to implement strategies, which specifically target more marginal populations and geographic areas. This also needs peace and stability, without which it is almost impossible to improve health

Recent ASA presidents and ‘top’ journals: observed publication patterns, alleged cartels and varying careers

It has been common for studies presented as about American sociology as a whole to rely on data compiled from leading journals (American Sociological Review [ASR] and American Journal of Sociology [AJS]), or about presidents of the American Sociological Association [ASA], to represent it. Clearly those are important, but neither can be regarded as providing a representative sample of American sociology. Recently, Stephen Turner has suggested that dominance in the ASA rests with a ‘cartel’ initially formed in graduate school, and that it favors work in a style associated with the leading journals. The adequacy of these ideas is examined in the light of available data on the last 20 years, which show that very few of the presidents were in the same graduate schools at the same time. All presidents have had distinguished academic records, but it is shown that their publication strategies have varied considerably. Some have had no ASR publications except their presidential addresses, while books and large numbers of other journals not normally mentioned in this context have figured in their contributions, as well as being more prominent in citations. It seems clear that articles in the leading journals have not been as closely tied to prestigious careers as has sometimes been suggested, and that if there is a cartel it has not included all the presidents

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Superlattices: problems and new opportunities, nanosolids

Superlattices were introduced 40 years ago as man-made solids to enrich the class of materials for electronic and optoelectronic applications. The field metamorphosed to quantum wells and quantum dots, with ever decreasing dimensions dictated by the technological advancements in nanometer regime. In recent years, the field has gone beyond semiconductors to metals and organic solids. Superlattice is simply a way of forming a uniform continuum for whatever purpose at hand. There are problems with doping, defect-induced random switching, and I/O involving quantum dots. However, new opportunities in component-based nanostructures may lead the field of endeavor to new heights. The all important translational symmetry of solids is relaxed and local symmetry is needed in nanosolids

Variations in the Difference between Mean Sea Level measured either side of Cape Hatteras and Their Relation to the North Atlantic Oscillation

We consider the extent to which the difference in mean sea level (MSL) measured on the North American Atlantic coast either side of Cape Hatteras varies as a consequence of dynamical changes in the ocean caused by fluctuations in the North Atlantic Oscillation (NAO). From analysis of tide gauge data, we know that changes in MSL-difference and NAO index are correlated on decadal to century timescales enabling a scale factor of MSL-difference change per unit change in NAO index to be estimated. Changes in trend in the NAO index have been small during the past few centuries (when measured using windows of order 60–120 years). Therefore, if the same scale factor applies through this period of time, the corresponding changes in trend in MSL-difference for the past few centuries should also have been small. It is suggested thereby that the sea level records for recent centuries obtained from salt marshes (adjusted for long-term vertical land movements) should have essentially the same NAO-driven trends south and north of Cape Hatteras, only differing due to contributions from other processes such as changes in the Meridional Overturning Circulation or ‘geophysical fingerprints’. The salt marsh data evidently support this interpretation within their uncertainties for the past few centuries, and perhaps even for the past millennium. Recommendations are made on how greater insight might be obtained by acquiring more measurements and by improved modelling of the sea level response to wind along the shelf

Point mutation of tyrosine 759 of the IL-6 family cytokine receptor, gp130, augments collagen-induced arthritis in DBA/1J mice

<p>Abstract</p> <p>Background</p> <p>Knock-in mice (gp130F759) with a Y759F point mutation in gp130, a signal transducing receptor subunit shared by members of the IL-6 cytokine family, show sustained activation of STAT3, enhanced acute-phase or immune responses, and autoimmune arthritis. We conducted a detailed analysis of collagen-induced arthritis (CIA) in gp130F759 with a DBA/1J background (D/J.gp130F759).</p> <p>Methods</p> <p>We backcrossed gp130F759 to C57BL/6 and DBA/1J, and compared the pathologic changes, including occurrence of arthritis, in the two distinct genetic backgrounds. We analyzed CIA in D/J.gp130F759 and investigated the effects of methotrexate (MTX) on CIA.</p> <p>Results</p> <p>C57BL/6 background gp130F759 mice, but not D/J.gp130F759, spontaneously developed polyarthritis and glomerulonephritis. On the other hand, keratitis of the eyes only developed in D/J.gp130F759, indicating the influence of genetic background on disease development in gp130F759 mice. Resistance of the DBA/1J background against spontaneous arthritis urged us to examine CIA in D/J.gp130F759. CIA in D/J.gp130F759 was more severe, with greater bone destruction, than the control mice. After collagen immunization, splenomegaly and serum levels of rheumatoid factor and anti-DNA antibody were augmented in D/J.gp130F759. Bio-Plex analysis of serum cytokines revealed increased IL-12p40 and PDGF-BB before immunization, and increased levels of IFN-γ, IL-17, TNF-α, IL-9, and MIP-1β 8 days after the booster dose. IL-6 and PDGF-BB in D/J.gp130F759 showed distinct kinetics from the other cytokines; higher levels were observed after arthritis development. MTX partially attenuated the development of arthritis and inhibited bone destruction in D/J.gp130F759, with reduction of anti-type II collagen antibody levels, suggesting that MTX mainly affects antigen-specific immune responses in CIA.</p> <p>Conclusion</p> <p>The Tyr-759 point mutation of the IL-6 family cytokine receptor subunit, gp130, caused autoimmune disease, and this was also influenced by the genetic background. CIA in D/J.gp130F759 is useful for evaluating drugs in a relatively short period because sustained activation of STAT3 may enhance the disease symptoms.</p

Targeting RNA Polymerase Primary σ70 as a Therapeutic Strategy against Methicillin-Resistant Staphylococcus aureus by Antisense Peptide Nucleic Acid

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL FINDINGS: By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. CONCLUSIONS: The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections

Development and validation of the Self-Regulation of Eating Behaviour Questionnaire for adults

Background Eating self-regulatory capacity can help individuals to cope with the obesogenic environment and achieve, as well as maintain, a healthy weight and diet. At present, there is no comprehensive, reliable and valid questionnaire for assessing this capacity and measuring change in response to self-regulation interventions in adults. This paper reports the development of the Self-regulation of Eating Behaviour Questionnaire (SREBQ) for use in UK adults, and presents evidence for its reliability and construct validity. The development of the SREBQ involved generation of an item pool, followed by two pilot studies (Samples 1 and 2) and a test of the questionnaire’s underlying factor structure (Sample 3). The final version of the SREBQ was then assessed for reliability and construct validity (Sample 4). Results Development of the SREBQ resulted in a 5-item questionnaire. The face validity was satisfactory, as assessed by the pilot studies. The factor structure analysis (Sample 3) suggested that it has a single underlying factor, which was confirmed in a second sample (Sample 4). The SREBQ had strong construct validity, showing a positive correlation with general measures of self-regulation. It was also positively correlated with motivation and behavioural automaticity, and negatively correlated with food responsiveness and emotional over-eating (p < 0.001). It showed good discriminant validity, as it was only weakly associated with satiety responsiveness, food fussiness and slowness in eating. Conclusions The SREBQ is a reliable and valid measure for assessment of eating self-regulatory capacity in the general UK adult population

Remarkable muscles, remarkable locomotion in desert-dwelling wildebeest

Large mammals that live in arid and/or desert environments can cope with seasonal and local variations in rainfall, food and climate1 by moving long distances, often without reliable water or food en route. The capacity of an animal for this long-distance travel is substantially dependent on the rate of energy utilization and thus heat production during locomotion—the cost of transport2,3,4. The terrestrial cost of transport is much higher than for flying (7.5 times) and swimming (20 times)4. Terrestrial migrants are usually large1,2,3 with anatomical specializations for economical locomotion5,6,7,8,9, because the cost of transport reduces with increasing size and limb length5,6,7. Here we used GPS-tracking collars10 with movement and environmental sensors to show that blue wildebeest (Connochaetes taurinus, 220 kg) that live in a hot arid environment in Northern Botswana walked up to 80 km over five days without drinking. They predominantly travelled during the day and locomotion appeared to be unaffected by temperature and humidity, although some behavioural thermoregulation was apparent. We measured power and efficiency of work production (mechanical work and heat production) during cyclic contractions of intact muscle biopsies from the forelimb flexor carpi ulnaris of wildebeest and domestic cows (Bos taurus, 760 kg), a comparable but relatively sedentary ruminant. The energetic costs of isometric contraction (activation and force generation) in wildebeest and cows were similar to published values for smaller mammals. Wildebeest muscle was substantially more efficient (62.6%) than the same muscle from much larger cows (41.8%) and comparable measurements that were obtained from smaller mammals (mouse (34%)11 and rabbit (27%)). We used the direct energetic measurements on intact muscle fibres to model the contribution of high working efficiency of wildebeest muscle to minimizing thermoregulatory challenges during their long migrations under hot arid conditions

Absence of N-terminal acetyltransferase diversification during evolution of eukaryotic organisms

Protein N-terminal acetylation is an ancient and ubiquitous co-translational modification catalyzed by a highly conserved family of N-terminal acetyltransferases (NATs). Prokaryotes have at least 3 NATs, whereas humans have six distinct but highly conserved NATs, suggesting an increase in regulatory complexity of this modification during eukaryotic evolution. Despite this, and against our initial expectations, we determined that NAT diversification did not occur in the eukaryotes, as all six major human NATs were most likely present in the Last Eukaryotic Common Ancestor (LECA). Furthermore, we also observed that some NATs were actually secondarily lost during evolution of major eukaryotic lineages; therefore, the increased complexity of the higher eukaryotic proteome occurred without a concomitant diversification of NAT complexes