Neighbourhood deprivation monitoring in Rotterdam and London: exploring barriers to evidence-based policy and practice

There is ample evidence that area-based approaches to tackling health inequalities, as part of a wider policy of community regeneration, are effective. Nevertheless, embedding this evidence in the routine practice of health professionals has not followed automatically. One of the barriers to the uptake of research is the process by which evidence is generated and its usability, or “stickiness”. This paper draws on the concept of stickiness to explore the role of deprivation monitoring data in creating an evidence base for neighbourhood health policies and intervention. The study was undertaken as part of a Knowledge Exchange Programme aimed at sharing learning to improve the participation and health of disadvantaged people in deprived neighbourhoods in Rotterdam and London. The two cities are similar in that they both have highly diverse populations and government health and social policies that employ area-based approaches to tackle deprivation. Documentary analysis and in-depth interviews with health professionals and policymakers in the two cities have explored the construction of health policy, the congruence between data on deprivation and the contextual experience of practitioners, and the factors that influenced the usability of the data

A Chromosome 7 Pericentric Inversion Defined at Single-Nucleotide Resolution Using Diagnostic Whole Genome Sequencing in a Patient with Hand-Foot-Genital Syndrome.

Next generation sequencing methodologies are facilitating the rapid characterisation of novel structural variants at nucleotide resolution. These approaches are particularly applicable to variants initially identified using alternative molecular methods. We report a child born with bilateral postaxial syndactyly of the feet and bilateral fifth finger clinodactyly. This was presumed to be an autosomal recessive syndrome, due to the family history of consanguinity. Karyotype analysis revealed a homozygous pericentric inversion of chromosome 7 (46,XX,inv(7)(p15q21)x2) which was confirmed to be heterozygous in both unaffected parents. Since the resolution of the karyotype was insufficient to identify any putatively causative gene, we undertook medium-coverage whole genome sequencing using paired-end reads, in order to elucidate the molecular breakpoints. In a two-step analysis, we first narrowed down the region by identifying discordant read-pairs, and then determined the precise molecular breakpoint by analysing the mapping locations of "soft-clipped" breakpoint-spanning reads. PCR and Sanger sequencing confirmed the identified breakpoints, both of which were located in intergenic regions. Significantly, the 7p15 breakpoint was located 523 kb upstream of HOXA13, the locus for hand-foot-genital syndrome. By inference from studies of HOXA locus control in the mouse, we suggest that the inversion has delocalised a HOXA13 enhancer to produce the phenotype observed in our patient. This study demonstrates how modern genetic diagnostic approach can characterise structural variants at nucleotide resolution and provide potential insights into functional regulation

Robust diagnostic genetic testing using solution capture enrichment and a novel variant-filtering interface.

Targeted hybridization enrichment prior to next-generation sequencing is a widespread method for characterizing sequence variation in a research setting, and is being adopted by diagnostic laboratories. However, the number of variants identified can overwhelm clinical laboratories with strict time constraints, the final interpretation of likely pathogenicity being a particular bottleneck. To address this, we have developed an approach in which, after automatic variant calling on a standard unix pipeline, subsequent variant filtering is performed interactively, using AgileExomeFilter and AgilePindelFilter (http://dna.leeds.ac.uk/agile), tools designed for clinical scientists with standard desktop computers. To demonstrate the method's diagnostic efficacy, we tested 128 patients using (1) a targeted capture of 36 cancer-predisposing genes or (2) whole-exome capture for diagnosis of the genetically heterogeneous disorder primary ciliary dyskinesia (PCD). In the cancer cohort, complete concordance with previous diagnostic data was achieved across 793 variant genotypes. A high yield (42%) was also achieved for exome-based PCD diagnosis, underscoring the scalability of our method. Simple adjustments to the variant filtering parameters further allowed the identification of a homozygous truncating mutation in a presumptive new PCD gene, DNAH8. These tools should allow diagnostic laboratories to expand their testing portfolios flexibly, using a standard set of reagents and techniques

Trabajo interinstitucional junto al Consorcio de Riego Campo Grande

Durante los años 2016 y 2017 se profundizo el trabajo en el sistema de riego de Campo Grande en forma conjunta entre INTA y DPA, con el objetivo de prestar asistencia técnica al Consorcio de Riego de Campo Grande (CRCG). Se desarrollaron jornadas de aforo y riego tendientes a fomentar el uso racional del agua y establecer acuerdos de uso entre productores frutícolas y hortícolas. Entre los objetivos que se plantearon fueron: acordar criterios de medición del agua de riego, lograr un uso racional del recurso hídrico, fomentar el trabajo conjunto y fortalecer las relaciones de trabajo entre tomeros, comisión directiva y usuarios.EEA Alto ValleFil: Storti, Cesar. Departamento Provincial de Aguas de Río Negro; ArgentinaFil: Merino Tosoni, María de la Paz. Departamento Provincial de Aguas de Río Negro; ArgentinaFil: Sheridan, Miguel Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Alto Valle. Agencia de Extensión Rural Cipolletti; ArgentinaFil: Gasparri, Emiliano. Consorcio de Riego de Campo Grande; Argentin

Challenges and Opportunities: What Can We Learn from Patients Living with Chronic Musculoskeletal Conditions, Health Professionals and Carers about the Concept of Health Literacy Using Qualitative Methods of Inquiry?

The field of health literacy continues to evolve and concern public health researchers and yet remains a largely overlooked concept elsewhere in the healthcare system. We conducted focus group discussions in England UK, about the concept of health literacy with older patients with chronic musculoskeletal conditions (mean age = 73.4 years), carers and health professionals. Our research posed methodological, intellectual and practical challenges. Gaps in conceptualisation and expectations were revealed, reiterating deficiencies in predominant models for understanding health literacy and methodological shortcomings of using focus groups in qualitative research for this topic. Building on this unique insight into what the concept of health literacy meant to participants, we present analysis of our findings on factors perceived to foster and inhibit health literacy and on the issue of responsibility in health literacy. Patients saw health literacy as a result of an inconsistent interactive process and the implications as wide ranging; healthcare professionals had more heterogeneous views. All focus group discussants agreed that health literacy most benefited from good inter-personal communication and partnership. By proposing a needs-based approach to health literacy we offer an alternative way of conceptualising health literacy to help improve the health of older people with chronic conditions

Unified View of Scaling Laws for River Networks

Scaling laws that describe the structure of river networks are shown to follow from three simple assumptions. These assumptions are: (1) river networks are structurally self-similar, (2) single channels are self-affine, and (3) overland flow into channels occurs over a characteristic distance (drainage density is uniform). We obtain a complete set of scaling relations connecting the exponents of these scaling laws and find that only two of these exponents are independent. We further demonstrate that the two predominant descriptions of network structure (Tokunaga's law and Horton's laws) are equivalent in the case of landscapes with uniform drainage density. The results are tested with data from both real landscapes and a special class of random networks.Comment: 14 pages, 9 figures, 4 tables (converted to Revtex4, PRE ref added

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Geometry of River Networks II: Distributions of Component Size and Number

The structure of a river network may be seen as a discrete set of nested sub-networks built out of individual stream segments. These network components are assigned an integral stream order via a hierarchical and discrete ordering method. Exponential relationships, known as Horton's laws, between stream order and ensemble-averaged quantities pertaining to network components are observed. We extend these observations to incorporate fluctuations and all higher moments by developing functional relationships between distributions. The relationships determined are drawn from a combination of theoretical analysis, analysis of real river networks including the Mississippi, Amazon and Nile, and numerical simulations on a model of directed, random networks. Underlying distributions of stream segment lengths are identified as exponential. Combinations of these distributions form single-humped distributions with exponential tails, the sums of which are in turn shown to give power law distributions of stream lengths. Distributions of basin area and stream segment frequency are also addressed. The calculations identify a single length-scale as a measure of size fluctuations in network components. This article is the second in a series of three addressing the geometry of river networks.Comment: 16 pages, 13 figures, 4 tables, Revtex4, submitted to PR

Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis.

The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3(+) regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation. Treg cell-specific ablation of HOIP causes severe Treg cell deficiency and lethal immune pathology, revealing an ongoing requirement of LUBAC activity for Treg cell homeostasis. These data reveal stage-specific requirements for LUBAC in coordinating the signals required for T-cell differentiation

Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination