Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance

From venture idea to venture formation:The role of sensemaking, sensegiving and sense receiving

This article explores the sensemaking processes entrepreneurs use when transitioning between venture ideas and venture formation. Adopting a sensemaking/sensegiving approach and utilising an interpretivist methodology, we use sensemaking to analyse the entrepreneurial journey of four diverse entrepreneurs. In so doing, we make three contributions: first, we locate the early stages of the entrepreneurial context as a primary site where sensemaking occurs as entrepreneurs deal with the differences between expectations and reality. Second, we show how sensemaking occurs when entrepreneurs build a causal map of the problem they wish to address and how social exchanges are crucial as entrepreneurs then refine that idea with other sensegivers. Finally, we extend scholarly understanding through explaining the ways in which sensemaking, sensegiving and sense receiving contribute to the entrepreneurs' decision to act and create a new venture

Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach

This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivors’ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the intervention’s Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions

Genome-wide methylation and gene expression changes in newborn rats following maternal protein restriction and reversal by folic acid

A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures

Whole number thinking, learning and development: neuro-cognitive, cognitive and developmental approaches

The participants of working group 2 presented a broad range of studies, 11 papers in total, related to whole number learning representing research groups from 11 countries as follows. Two large cross-sectional studies focused on developmental aspects of young children’s number learning provide a lens for re-examining ‘traditional’ features of number acquisition. van den Heuvel-Panhuizen (the Netherlands) presented a co-authored paper with Elia (Cyprus; Elia and van den Heuvel-Panhuizen 2015) on a cross-cultural study of kindergartners’ number competence focused on counting, additive and multiplicative thinking. Second, Milinković (2015) examined the development of young Serbian children’s initial understanding of representations of whole numbers and counting strategies in a large study of 3- to 7-year-olds. Children’s invented (formal) representations such as set representation and the number line were found to be limited in their recordings. In a South African study focused on early counting and addition, Roberts (2015) directs attention to the role of teachers by providing a framework to support teachers’ interpretation of young disadvantaged learners’ representations of number when engaging with whole number additive tasks. Some papers reflected the increasing role of neuroscientific concepts and methodologies utilised in research on WNA learning and development. Sinclair and Coles (2015) drew upon neuroscientific research to highlight the significant role of symbol-to-symbol connections and the use of fingers and touch counting exempli- fied by the TouchCounts iPad app. Gould (2015) reported aspects of a large Australian large study of children in the first years of schooling aimed at improving numeracy and literacy in disadvantaged communities. A case study exemplified how numerals were identified by relying on a mental number line by using location to retrieve number names. This raised the question addressed in the neuroscientific work of Dehaene and other papers focused on individual differences in how the brain processes numbers. The Italian PerContare1 project (Baccaglini-Frank 2015) built upon the collaboration between cognitive psychologists and mathematics educators, aimed at developing teaching strategies for preventing and addressing early low achievement in arithmetic. It takes an innovative approach to the development of number sense that is grounded upon a kinaesthetic and visual-spatial approach to part-whole relationships. Mulligan and Woolcott (2015) provided a discussion paper on the underlying nature of number. They presented a broader view of mathematics learning (including WNA) as linked to spatial interaction with the environment; the concept of connectivity across concepts and the development of underlying pattern and structural relationships are central to their approach

Evidence and argument in policymaking: development of workplace smoking legislation

<p>Abstract</p> <p>Background</p> <p>We sought to identify factors that affect the passage of public health legislation by examining the use of arguments, particularly arguments presenting research evidence, in legislative debates regarding workplace smoking restrictions.</p> <p>Methods</p> <p>We conducted a case-study based content analysis of legislative materials used in the development of six state workplace smoking laws, including written and spoken testimony and the text of proposed and passed bills and amendments. We coded testimony given before legislators for arguments used, and identified the institutional affiliations of presenters and their position on the legislation. We compared patterns in the arguments made in testimony to the relative strength of each state's final legislation.</p> <p>Results</p> <p>Greater discussion of scientific evidence within testimony given was associated with the passage of workplace smoking legislation that provided greater protection for public health, regardless of whether supporters outnumbered opponents or vice versa.</p> <p>Conclusion</p> <p>Our findings suggest that an emphasis on scientific discourse, relative to other arguments made in legislative testimony, might help produce political outcomes that favor public health.</p

Exhaustive exercise training enhances aerobic capacity in American alligator (Alligator mississippiensis)

The oxygen transport system in mammals is extensively remodelled in response to repeated bouts of activity, but many reptiles appear to be ‘metabolically inflexible’ in response to exercise training. A recent report showed that estuarine crocodiles (Crocodylus porosus) increase their maximum metabolic rate in response to exhaustive treadmill training, and in the present study, we confirm this response in another crocodilian, American alligator (Alligator mississippiensis). We further specify the nature of the crocodilian training response by analysing effects of training on aerobic [citrate synthase (CS)] and anaerobic [lactate dehydrogenase (LDH)] enzyme activities in selected skeletal muscles, ventricular and skeletal muscle masses and haematocrit. Compared to sedentary control animals, alligators regularly trained for 15 months on a treadmill (run group) or in a flume (swim group) exhibited peak oxygen consumption rates higher by 27 and 16%, respectively. Run and swim exercise training significantly increased ventricular mass (~11%) and haematocrit (~11%), but not the mass of skeletal muscles. However, exercise training did not alter CS or LDH activities of skeletal muscles. Similar to mammals, alligators respond to exercise training by increasing convective oxygen transport mechanisms, specifically heart size (potentially greater stroke volume) and haematocrit (increased oxygen carrying-capacity of the blood). Unlike mammals, but similar to squamate reptiles, alligators do not also increase citrate synthase activity of the skeletal muscles in response to exercise

Nitroxyl (HNO) Stimulates Soluble Guanylyl Cyclase to Suppress Cardiomyocyte Hypertrophy and Superoxide Generation

Background: New therapeutic targets for cardiac hypertrophy, an independent risk factor for heart failure and death, are essential. HNO is a novel redox sibling of NON attracting considerable attention for the treatment of cardiovascular disorders, eliciting cGMP-dependent vasodilatation yet cGMP-independent positive inotropy. The impact of HNO on cardiac hypertrophy (which is negatively regulated by cGMP) however has not been investigated. Methods: Neonatal rat cardiomyocytes were incubated with angiotensin II (Ang II) in the presence and absence of the HNO donor Angeli’s salt (sodium trioxodinitrate) or B-type natriuretic peptide, BNP (all 1 mmol/L). Hypertrophic responses and its triggers, as well as cGMP signaling, were determined. Results: We now demonstrate that Angeli’s salt inhibits Ang II-induced hypertrophic responses in cardiomyocytes, including increases in cardiomyocyte size, de novo protein synthesis and b-myosin heavy chain expression. Angeli’s salt also suppresses Ang II induction of key triggers of the cardiomyocyte hypertrophic response, including NADPH oxidase (on both Nox2 expression and superoxide generation), as well as p38 mitogen-activated protein kinase (p38MAPK). The antihypertrophic, superoxide-suppressing and cGMP-elevating effects of Angeli’s salt were mimicked by BNP. We also demonstrate that the effects of Angeli’s salt are specifically mediated by HNO (with no role for NON or nitrite), with subsequent activation of cardiomyocyte soluble guanylyl cyclase (sGC) and cGMP signaling (on both cGMP-dependen

The genome-wide dynamics of purging during selfing in maize

Self-fertilization (also known as selfing) is an important reproductive strategy in plants and a widely applied tool for plant genetics and plant breeding. Selfing can lead to inbreeding depression by uncovering recessive deleterious variants, unless these variants are purged by selection. Here we investigated the dynamics of purging in a set of eleven maize lines that were selfed for six generations. We show that heterozygous, putatively deleterious single nucleotide polymorphisms are preferentially lost from the genome during selfing. Deleterious single nucleotide polymorphisms were lost more rapidly in regions of high recombination, presumably because recombination increases the efficacy of selection by uncoupling linked variants. Overall, heterozygosity decreased more slowly than expected, by an estimated 35% to 40% per generation instead of the expected 50%, perhaps reflecting pervasive associative overdominance. Finally, three lines exhibited marked decreases in genome size due to the purging of transposable elements. Genome loss was more likely to occur for lineages that began with larger genomes with more transposable elements and chromosomal knobs. These three lines purged an average of 398 Mb from their genomes, an amount equivalent to three Arabidopsis thaliana genomes per lineage, in only a few generations

Effects of the fungicide metiram in outdoor freshwater microcosms: responses of invertebrates, primary producers and microbes

The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT50) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOECcommunity = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOECmicrocosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks)