Impacts of Climate Change on indirect human exposure to pathogens and chemicals from agriculture

Objective: Climate change is likely to affect the nature of pathogens and chemicals in the environment and their fate and transport. Future risks of pathogens and chemicals could therefore be very different from those of today. In this review, we assess the implications of climate change for changes in human exposures to pathogens and chemicals in agricultural systems in the United Kingdom and discuss the subsequent effects on health impacts. Data sources: In this review, we used expert input and considered literature on climate change ; health effects resulting from exposure to pathogens and chemicals arising from agriculture ; inputs of chemicals and pathogens to agricultural systems ; and human exposure pathways for pathogens and chemicals in agricultural systems. Data synthesis: We established the current evidence base for health effects of chemicals and pathogens in the agricultural environment ; determined the potential implications of climate change on chemical and pathogen inputs in agricultural systems ; and explored the effects of climate change on environmental transport and fate of different contaminant types. We combined these data to assess the implications of climate change in terms of indirect human exposure to pathogens and chemicals in agricultural systems. We then developed recommendations on future research and policy changes to manage any adverse increases in risks. Conclusions: Overall, climate change is likely to increase human exposures to agricultural contaminants. The magnitude of the increases will be highly dependent on the contaminant type. Risks from many pathogens and particulate and particle-associated contaminants could increase significantly. These increases in exposure can, however, be managed for the most part through targeted research and policy changes

Fair publication of qualitative research in health systems: a call by health policy and systems researchers.

[Extract] An open letter from Trisha Greenhalgh et al. [1] to the editors of the British Medical Journal (BMJ) triggered wide debate by health policy and systems researchers (HPSRs) globally on the inadequate recognition of the value of qualitative research and the resulting deficit in publishing papers reporting on qualitative research [2]. One key dimension of equity in health is that researchers are able to disseminate their findings and that they are taken into account in a fair and just manner, so that they can inform health policy and programmes. The Greenhalgh et al. letter and editorial responses [3, 4] were actively discussed within "SHAPES", a thematic group within Health Systems Global, focused on Social Science approaches for research and engagement in health policy & systems (http://healthsystemsglobal.org/twg-group/6/Social-science-approaches-for-research-and-engagement-in-health-policy-amp-systems/) and within EQUINET, a regional network working on health equity research in East and Southern Africa (www.equinetafrica.org). Our discussion precipitated in this follow up open letter/commentary, which has 170 co-signatories. Collectively, we feel that barriers to publication of qualitative research limit publication of many exemplary studies, and their contribution to understanding important dimensions of health care, services, policies and systems

Multidecadal Remote Sensing of Inland Water Dynamics

Remote sensing approaches to measuring inland water dynamics date back more than 50 years. These approaches rely on the unique spectral properties of different waterbodies to delineate surface extents and estimate optically active water quality parameters. Until recently, inland water remote sensing focused largely on localized study domains due to limitations in modelling methods, computing power, and data access. Recent advances in these areas have created novel opportunities for data-driven-multidecadal remote sensing of inland waters at the landscape scale. Here, I highlight the history of inland water remote sensing along with the dominant methodologies, water quality constituents, and limitations involved. I then use this background to contextualize three macroscale inland water remote sensing studies of increasing complexity. The first combines field measurements with remotely sensed surface water extents to identify the impacts of small-scale gold mining in Peru. Our results suggest that mining is leading to synergistic increases in lake area and mercury loading that are significantly heightening exposure risk for people and wildlife. I move from measuring lake extents in Peru to measuring lake color in over 26,000 lakes across the United States. This analysis shows that lake color seasonality can be generalized into five distinct phenology groups that follow well-known patterns of algae growth and succession. The stability of a given lake (i.e. the likelihood it will move from one phenology group to another) is tied to lake and landscape level characteristics including climate and population density. Finally, I move from simple parameters such as quantity and color to estimating multidecadal changes in water clarity in U.S. lakes. I show that lake water clarity in the U.S. has increased by an average of 0.52 cm yr-1 since 1984, largely as a result of extensive U.S. freshwater pollution abatement measures. In combination, these three studies highlight that data intensive remote sensing approaches are expanding the capabilities of inland water remote sensing from local to global scales, and that macroscale remote sensing of inland waters reveals trends and processes that are unobservable using field data alone.Doctor of Philosoph

Land cover change and carbon emissions over 100 years in an African biodiversity hotspot

Agricultural expansion has resulted in both land use and land cover change (LULCC) across the tropics. However, the spatial and temporal patterns of such change and their resulting impacts are poorly understood, particularly for the pre-satellite era. Here we quantify the LULCC history across the 33.9 million ha watershed of Tanzania's Eastern Arc Mountains, using geo-referenced and digitised historical land cover maps (dated 1908, 1923, 1949 and 2000). Our time series from this biodiversity hotspot shows that forest and savanna area both declined, by 74% (2.8 million ha) and 10% (2.9 million ha), respectively, between 1908 and 2000. This vegetation was replaced by a five-fold increase in cropland, from 1.2 million ha to 6.7 million ha. This LULCC implies a committed release of 0.9 Pg C (95% CI: 0.4-1.5) across the watershed for the same period, equivalent to 0.3 Mg C ha(-1) yr(-1) . This is at least three-fold higher than previous estimates from global models for the same study area. We then used the LULCC data from before and after protected area creation, as well as from areas where no protection was established, to analyse the effectiveness of legal protection on land cover change despite the underlying spatial variation in protected areas. We found that, between 1949 and 2000, forest expanded within legally protected areas, resulting in carbon uptake of 4.8 (3.8-5.7) Mg C ha(-1) , compared to a committed loss of 11.9 (7.2-16.6) Mg C ha(-1) within areas lacking such protection. Furthermore, for nine protected areas where LULCC data is available prior to and following establishment, we show that protection reduces deforestation rates by 150% relative to unprotected portions of the watershed. Our results highlight that considerable LULCC occurred prior to the satellite era, thus other data sources are required to better understand long-term land cover trends in the tropics. This article is protected by copyright. All rights reserved

GacA is essential for Group A <i>Streptococcus </i>and defines a new class of monomeric dTDP-4-dehydrorhamnose reductases (RmlD)

The sugar nucleotide dTDP-L-rhamnose is critical for the biosynthesis of the Group A Carbohydrate, the molecular signature and virulence determinant of the human pathogen Group A Streptococcus (GAS). The final step of the four-step dTDP-L-rhamnose biosynthesis pathway is catalyzed by dTDP-4-dehydrorhamnose reductases (RmlD). RmlD from the Gram-negative bacterium Salmonella is the only structurally characterized family member and requires metal-dependent homo-dimerization for enzymatic activity. Using a biochemical and structural biology approach, we demonstrate that the only RmlD homologue from GAS, previously renamed GacA, functions in a novel monomeric manner. Sequence analysis of 213 Gram-negative and Gram-positive RmlD homologues predicts that enzymes from all Gram-positive species lack a dimerization motif and function as monomers. The enzymatic function of GacA was confirmed through heterologous expression of gacA in a S. mutans rmlD knockout, which restored attenuated growth and aberrant cell division. Finally, analysis of a saturated mutant GAS library using Tn-sequencing and generation of a conditional-expression mutant identified gacA as an essential gene for GAS. In conclusion, GacA is an essential monomeric enzyme in GAS and representative of monomeric RmlD enzymes in Gram-positive bacteria and a subset of Gram-negative bacteria. These results will help future screens for novel inhibitors of dTDP-L-rhamnose biosynthesis

Exploring the Feasibility of Service Integration in a Low-Income Setting: A Mixed Methods Investigation into Different Models of Reproductive Health and HIV Care in Swaziland.

Integrating reproductive health (RH) with HIV care is a policy priority in high HIV prevalence settings, despite doubts surrounding its feasibility and varying evidence of effects on health outcomes. The process and outcomes of integrated RH-HIV care were investigated in Swaziland, through a comparative case study of four service models, ranging from fully integrated to fully stand-alone HIV services, selected purposively within one town. A client exit survey (n=602) measured integrated care received and unmet family planning (FP) needs. Descriptive statistics were used to assess the degree of integration per clinic and client demand for services. Logistic regression modelling was used to test the hypothesis that clients at more integrated sites had lower unmet FP needs than clients in a stand-alone site. Qualitative methods included in-depth interviews with clients and providers to explore contextual factors influencing the feasibility of integrated RH-HIV care delivery; data were analysed thematically, combining deductive and inductive approaches. Results demonstrated that clinic models were not as integrated in practice as had been claimed. Fragmentation of HIV care was common. Services accessed per provider were no higher at the more integrated clinics compared to stand-alone models (p>0.05), despite reported demand. While women at more integrated sites received more FP and pregnancy counselling than stand-alone models, they received condoms (a method of choice) less often, and there was no statistical evidence of difference in unmet FP needs by model of care. Multiple contextual factors influenced integration practices, including provider de-skilling within sub-specialist roles; norms of task-oriented routinised HIV care; perceptions of heavy client loads; imbalanced client-provider interactions hindering articulation of RH needs; and provider motivation challenges. Thus, despite institutional support, factors related to the social context of care inhibited provision of fully integrated RH-HIV services in these clinics. Programmes should move beyond simplistic training and equipment provision if integrated care interventions are to be sustained

Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS

Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant ‘steric zipper’ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone

SOD1-ALS-Browser:a web-utility for investigating the clinical phenotype in SOD1 amyotrophic lateral sclerosis

Objective: Variants in the superoxide dismutase (SOD1) gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has become clear that SOD1-linked ALS presents a highly variable age at symptom onset and disease duration.Methods: Here we describe an open access web tool for comparative phenotype analysis in ALS: https://sod1-als-browser.rosalind.kcl.ac.uk/. The tool contains a built-in dataset of clinical information from 1383 people with ALS harboring a SOD1 variant resulting in one of 162 unique amino acid sequence alterations and from a non-SOD1 comparator ALS cohort of 13,469 individuals. We present two examples of analyses possible with this tool, testing how the ALS phenotype relates to SOD1 variants that alter amino acid residue hydrophobicity and to distinct variants at the 94th residue of SOD1, where six are sampled.Results and conclusions: The tool provides immediate access to the datasets and enables bespoke analysis of phenotypic trends associated with different protein variants, including the option for users to upload their own datasets for integration with the server data. The tool can be used to study SOD1-ALS and provides an analytical framework to study the differences between other user-uploaded ALS groups and our large reference database of SOD1 and non-SOD1 ALS. The tool is designed to be useful for clinicians and researchers, including those without programming expertise, and is highly flexible in the analyses that can be conducted.</p

Measurement of the forward Z boson production cross-section in pp collisions at s=13\sqrt{s} = 13 TeV

A measurement of the production cross-section of Z bosons in pp collisions at $\sqrt{s} = 13$ TeV is presented using dimuon and dielectron final states in LHCb data. The cross-section is measured for leptons with pseudorapidities in the range $2.0 \eta 4.5$, transverse momenta $p_\text{T} 20$ GeV and dilepton invariant mass in the range $60 m(\ell\ell) 120$ GeV. The integrated cross-section from averaging the two final states is \begin{equation*}\sigma_{\text{Z}}^{\ell\ell} = 194.3 \pm 0.9 \pm 3.3 \pm 7.6\text{ pb,}\end{equation*} where the first uncertainty is statistical, the second is due to systematic effects, and the third is due to the luminosity determination. In addition, differential cross-sections are measured as functions of the Z boson rapidity, transverse momentum and the angular variable $\phi^*_\eta$

The role of positive selection in determining the molecular cause of species differences in disease

Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes