How effective are on-farm conservation land management strategies for preserving ecosystem services in developing countries? A systematic map protocol

Background An extensive body of literature in the field of agro-ecology claims to show the positive effects that maintenance of ecosystem services can have on sustainably meeting future food demand, by making farms more productive and resilient, and contributing to better nutrition and livelihoods of farmers. In Africa alone, some research has estimated a two-fold yield increase if food producers capitalize on new and existing knowledge from science and technology. Site-specific strategies adopted with the aim of improving ecosystem services may incorporate principles of multifunctional agriculture, sustainable intensification and conservation agriculture. However, a coherent synthesis and review of the evidence of these claims is largely absent, and the quality of much of this literature is questionable. Moreover, inconsistent effects have commonly been reported, while empirical evidence to support assumed improvements is largely lacking. Objectives This systematic map is stimulated by an interest to (1) collate evidence on the effectiveness of on-farm conservation land management for preserving and enhancing ecosystem services in agricultural landscapes, by drawing together the currently fragmented and multidisciplinary literature base, and (2) geographically map what indicators have been used to assess on-farm conservation land management. For both questions, we will focus on 74 low-income and developing countries, where much of the world’s agricultural expansion is occurring, yet 80% of arable land is already used and croplands are yielding well below their potential. Methods/Design To this end, reviewers will systematically search bibliographic databases for peer-reviewed research from Web of Science, SCOPUS, AGRICOLA, AGRIS databases and CAB abstracts, and grey literature from Google Scholar, and 22 subject-specific or institutional websites. Boolean search operators will be used to create search strings where applicable. Ecosystem services included in the study are pollination services; pest-, carbon-, soil-, and water-regulation; nutrient cycling; medicinal and aromatic plants; fuel wood and cultural services. Outputs of the systematic map will include a database, technical report and an online interactive map, searchable by topic. The results of this map are expected to provide clarity about synergistic outcomes of conservation land management, which will help support local decision-making

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential prognostic marker in human breast cancer

INTRODUCTION: ISG15 is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. However, alterations in the ISG15 signalling pathway have also been found in several human tumour entities. To the best of our knowledge, in the current study we present for the first time a systematic characterisation of ISG15 expression in human breast cancer and normal breast tissue both at the mRNA and protein level. METHOD: Using semiquantitative real-time PCR, cDNA dot-blot hybridisation and immunohistochemistry, we systematically analysed ISG15 expression in invasive breast carcinomas (n = 910) and normal breast tissues (n = 135). ISG15 protein expression was analysed in two independent cohorts on tissue microarrays; in an initial evaluation set of 179 breast carcinomas and 51 normal breast tissues; and in a second large validation set of 646 breast carcinomas and 10 normal breast tissues. In addition, a collection of benign and malignant mammary cell lines (n = 9) were investigated for ISG15 expression. RESULTS: ISG15 was overexpressed in breast carcinoma cells compared with normal breast tissue, both at the RNA and protein level. Recurrence-free (p = 0.030), event-free (p = 0.001) and overall (p = 0.001) survival analyses showed a significant correlation between ISG15 overexpression and unfavourable prognosis. CONCLUSION: Therefore, ISG15 may represent a novel breast tumour marker with prognostic significance and may be helpful in selecting patients for and predicting response to the treatment of human breast cancer

Association between community health center and rural health clinic presence and county-level hospitalization rates for ambulatory care sensitive conditions: an analysis across eight US states

<p>Abstract</p> <p>Background</p> <p>Federally qualified community health centers (CHCs) and rural health clinics (RHCs) are intended to provide access to care for vulnerable populations. While some research has explored the effects of CHCs on population health, little information exists regarding RHC effects. We sought to clarify the contribution that CHCs and RHCs may make to the accessibility of primary health care, as measured by county-level rates of hospitalization for ambulatory care sensitive (ACS) conditions.</p> <p>Methods</p> <p>We conducted an ecologic analysis of the relationship between facility presence and county-level hospitalization rates, using 2002 discharge data from eight states within the US (579 counties). Counties were categorized by facility availability: CHC(s) only, RHC(s) only, both (CHC and RHC), and neither. US Agency for Healthcare Research and Quality definitions were used to identify ACS diagnoses. Discharge rates were based on the individual's county of residence and were obtained by dividing ACS hospitalizations by the relevant county population. We calculated ACS rates separately for children, working age adults, and older individuals, and for uninsured children and working age adults. To ensure stable rates, we excluded counties having fewer than 1,000 residents in the child or working age adult categories, or 500 residents among those 65 and older. Multivariate Poisson analysis was used to calculate adjusted rate ratios.</p> <p>Results</p> <p>Among working age adults, rate ratio (RR) comparing ACS hospitalization rates for CHC-only counties to those of counties with neither facility was 0.86 (95% Confidence Interval, CI, 0.78–0.95). Among older adults, the rate ratio for CHC-only counties compared to counties with neither facility was 0.84 (CI 0.81–0.87); for counties with both CHC and RHC present, the RR was 0.88 (CI 0.84–0.92). No CHC/RHC effects were found for children. No effects were found on estimated hospitalization rates among uninsured populations.</p> <p>Conclusion</p> <p>Our results suggest that CHCs and RHCs may play a useful role in providing access to primary health care. Their presence in a county may help to limit the county's rate of hospitalization for ACS diagnoses, particularly among older people.</p

Insect Pollinated Crops, Insect Pollinators and US Agriculture: Trend Analysis of Aggregate Data for the Period 1992–2009

In the US, the cultivated area (hectares) and production (tonnes) of crops that require or benefit from insect pollination (directly dependent crops: apples, almonds, blueberries, cucurbits, etc.) increased from 1992, the first year in this study, through 1999 and continued near those levels through 2009; aggregate yield (tonnes/hectare) remained unchanged. The value of directly dependent crops attributed to all insect pollination (2009 USD) decreased from $14.29 billion in 1996, the first year for value data in this study, to$10.69 billion in 2001, but increased thereafter, reaching $15.12 billion by 2009. The values attributed to honey bees and non-Apis pollinators followed similar patterns, reaching$11.68 billion and $3.44 billion, respectively, by 2009. The cultivated area of crops grown from seeds resulting from insect pollination (indirectly dependent crops: legume hays, carrots, onions, etc.) was stable from 1992 through 1999, but has since declined. Production of those crops also declined, albeit not as rapidly as the decline in cultivated area; this asymmetry was due to increases in aggregate yield. The value of indirectly dependent crops attributed to insect pollination declined from$15.45 billion in 1996 to $12.00 billion in 2004, but has since trended upward. The value of indirectly dependent crops attributed to honey bees and non-Apis pollinators, exclusive of alfalfa leafcutter bees, has declined since 1996 to$5.39 billion and $1.15 billion, respectively in 2009. The value of alfalfa hay attributed to alfalfa leafcutter bees ranged between$4.99 and $7.04 billion. Trend analysis demonstrates that US producers have a continued and significant need for insect pollinators and that a diminution in managed or wild pollinator populations could seriously threaten the continued production of insect pollinated crops and crops grown from seeds resulting from insect pollination

A "Candidate-Interactome" Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a “candidate interactome” (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

A “Candidate-Interactome” Aggregate Analysis of Genome-Wide Association Data in Multiple Sclerosis

Though difficult, the study of gene-environment interactions in multifactorial diseases is crucial for interpreting the relevance of non-heritable factors and prevents from overlooking genetic associations with small but measurable effects. We propose a "candidate interactome" (i.e. a group of genes whose products are known to physically interact with environmental factors that may be relevant for disease pathogenesis) analysis of genome-wide association data in multiple sclerosis. We looked for statistical enrichment of associations among interactomes that, at the current state of knowledge, may be representative of gene-environment interactions of potential, uncertain or unlikely relevance for multiple sclerosis pathogenesis: Epstein-Barr virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, HHV8-Kaposi sarcoma, H1N1-influenza, JC virus, human innate immunity interactome for type I interferon, autoimmune regulator, vitamin D receptor, aryl hydrocarbon receptor and a panel of proteins targeted by 70 innate immune-modulating viral open reading frames from 30 viral species. Interactomes were either obtained from the literature or were manually curated. The P values of all single nucleotide polymorphism mapping to a given interactome were obtained from the last genome-wide association study of the International Multiple Sclerosis Genetics Consortium & the Wellcome Trust Case Control Consortium, 2. The interaction between genotype and Epstein Barr virus emerges as relevant for multiple sclerosis etiology. However, in line with recent data on the coexistence of common and unique strategies used by viruses to perturb the human molecular system, also other viruses have a similar potential, though probably less relevant in epidemiological terms

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe