Quantifying research output on poverty and non-communicable disease behavioural risk factors in low-income and lower middle-income countries: a bibliometric analysis

Objectives Low-income and lower middle-income countries (LLMICs) bear a disproportionate burden of non-communicable diseases (NCDs). WHO has repeatedly called for more research on poverty and NCDs in these settings, but the current situation remains unquantified. We aimed to assess research output on poverty and NCD risk factors from these countries in relation to upper middle-income and high-income countries. Design Bibliometric analysis of primary research published between 1 January 1990 and 4 May 2017. We searched 13 databases, combining terms for poverty and NCD behavioural risk factors (tobacco, alcohol, diet and physical activity). Independent dual review was used to screen titles, abstracts and full papers. Two-tailed t-testing and multiple linear regression analyses were used to compare differences in means. Outcomes (1) Proportion of lead authors affiliated with institutions based in high and upper middle-income countries vs LLMICs. (2) Mean number of citations for publications from each region. (3) Mean journal impact factor for studies from each region. Results Ninety-one (67%) of the 136 included studies were led by scientists affiliated with LLMIC-based institutions. These authors represented 17/83 LLMICs (20%), and their studies garnered 4.8 fewer citations per paper than studies led by high-income and upper middle-income-affiliated authors; however, this finding was non-significant (P=0.67). Papers led by authors based in high-income and upper middle-income countries were published in journals with a mean impact factor 3.1 points higher than those from LLMICs (4.9 vs 1.7) adjusting for year of publication and number of citations (P<0.001). Conclusions Most poverty and NCD risk factor research is led by authors from a small number of LLMICs. These studies are being published in relatively low-impact journals, and the vast majority of LLMICs are not producing any research in this area that is vital to their social and economic development. The paucity of domestic evidence must be addressed to inform global policy

Size effects and economies of scale in European real estate companies

This study investigates scale economies in European real estate companies. We examine the effects of size on revenue, expense, profitability ratios and capital costs using panel data regression. We find that larger real estate companies in Europe are able to generate higher revenue per unit of company size, incur lower costs and produce higher returns. Net Operating Income ratios and return ratios increase while Selling, General and Administrative expense ratios decrease with the size of a company. However, we do not find evidence that larger companies have lower cost of debt or lower weighted average cost of capital. From our analysis, it is evident that particularly small firms can reap substantial economies of scale as they grow. However, the benefits of further growth tend to be much more modest for larger companies. Given REITs are on average larger than comparable non-REITs this may explain why REITs have lower economies of scale in expenses and revenues than Non-REIT real estate companies

Combining exercise with cognitive training and vitamin D

Changes in functional brain connectivity (FBC) may indicate how lifestyle modifications can prevent the progression to dementia; FBC identifies areas that are spatially separate but temporally synchronized in their activation and is altered in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive aging and dementia. Participants with MCI were randomly assigned to one of five study arms. Three times per week for 20-weeks, participants performed 30-min of (control) cognitive training, followed by 60-min of (control) physical exercise. Additionally, a vitamin

Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey

Objective To establish with improved accuracy the prevalence of disease related prion protein (PrPCJD) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD)

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency &gt;3%, and were also present in the mutant library, had fitness levels that were &gt;40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Appropriateness of clinical severity classification of new WHO childhood pneumonia guidance : a multi-hospital, retrospective, cohort study

Background: Management of pneumonia in many low-income and middle-income countries is based on WHO guidelines that classify children according to clinical signs that define thresholds of risk. We aimed to establish whether some children categorised as eligible for outpatient treatment might have a risk of death warranting their treatment in hospital. Methods: We did a retrospective cohort study of children aged 2–59 months admitted to one of 14 hospitals in Kenya with pneumonia between March 1, 2014, and Feb 29, 2016, before revised WHO pneumonia guidelines were adopted in the country. We modelled associations with inpatient mortality using logistic regression and calculated absolute risks of mortality for presenting clinical features among children who would, as part of revised WHO pneumonia guidelines, be eligible for outpatient treatment (non-severe pneumonia). Findings: We assessed 16 162 children who were admitted to hospital in this period. 832 (5%) of 16 031 children died. Among groups defined according to new WHO guidelines, 321 (3%) of 11 788 patients with non-severe pneumonia died compared with 488 (14%) of 3434 patients with severe pneumonia. Three characteristics were strongly associated with death of children retrospectively classified as having non-severe pneumonia: severe pallor (adjusted risk ratio 5·9, 95% CI 5·1–6·8), mild to moderate pallor (3·4, 3·0–3·8), and weight-for-age Z score (WAZ) less than −3 SD (3·8, 3·4–4·3). Additional factors that were independently associated with death were: WAZ less than −2 to −3 SD, age younger than 12 months, lower chest wall indrawing, respiratory rate of 70 breaths per min or more, female sex, admission to hospital in a malaria endemic region, moderate dehydration, and an axillary temperature of 39°C or more. Interpretation: In settings of high mortality, WAZ less than −3 SD or any degree of pallor among children with non-severe pneumonia was associated with a clinically important risk of death. Our data suggest that admission to hospital should not be denied to children with these signs and we urge clinicians to consider these risk factors in addition to WHO criteria in their decision making

A Viral Discovery Methodology for Clinical Biopsy Samples Utilising Massively Parallel Next Generation Sequencing

Here we describe a virus discovery protocol for a range of different virus genera, that can be applied to biopsy-sized tissue samples. Our viral enrichment procedure, validated using canine and human liver samples, significantly improves viral read copy number and increases the length of viral contigs that can be generated by de novo assembly. This in turn enables the Illumina next generation sequencing (NGS) platform to be used as an effective tool for viral discovery from tissue samples

Ancient DNA and deep population structure in sub-Saharan African foragers

Multiple lines of genetic and archaeological evidence suggest that there were major demographic changes in the terminal Late Pleistocene epoch and early Holocene epoch of sub-Saharan Africa(1-4). Inferences about this period are challenging to make because demographic shifts in the past 5,000 years have obscured the structures of more ancient populations(3,5). Here we present genome-wide ancient DNA data for six individuals from eastern and south-central Africa spanning the past approximately 18,000 years (doubling the time depth of sub-Saharan African ancient DNA), increase the data quality for 15 previously published ancient individuals and analyse these alongside data from 13 other published ancient individuals. The ancestry of the individuals in our study area can be modelled as a geographically structured mixture of three highly divergent source populations, probably reflecting Pleistocene interactions around 80-20 thousand years ago, including deeply diverged eastern and southern African lineages, plus a previously unappreciated ubiquitous distribution of ancestry that occurs in highest proportion today in central African rainforest hunter-gatherers. Once established, this structure remained highly stable, with limited long-range gene flow. These results provide a new line of genetic evidence in support of hypotheses that have emerged from archaeological analyses but remain contested, suggesting increasing regionalization at the end of the Pleistocene epoch. DNA analysis of 6 individuals from eastern and south-central Africa spanning the past approximately 18,000 years, and of 28 previously published ancient individuals, provides genetic evidence supporting hypotheses of increasing regionalization at the end of the Pleistocene.info:eu-repo/semantics/publishedVersio

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead