A Cost-Effectiveness Protocol for Flood-Mitigation Plans Based on Leeds’ Boxing Day 2015 Floods

Inspired by the Boxing Day 2015 flood of the River Aire in Leeds, UK, and subsequent attempts to mitigate adverse consequences of flooding, the goals considered are: (i) to revisit the concept of flood-excess volume (FEV) as a complementary diagnostic for classifying flood events; (ii) to establish a new roadmap/protocol for assessing flood-mitigation schemes using FEV; and, (iii) to provide a clear, graphical cost-effectiveness analysis of flood mitigation, exemplified for a hypothetical scheme partially based on actual plans. We revisit the FEV concept and present it as a three-panel graph using thresholds and errors. By re-expressing FEV as a 2m -deep square lake of equivalent capacity, one can visualise its dimensions in comparison with the river valley considered. Cost-effectiveness of flood-mitigation measures is expressed within the FEV square-lake; different scenarios of our hypothetical flood-mitigation scheme are then presented and assessed graphically, with each scenario involving a combination, near and further upstream of Leeds, of higher (than existing) flood-defence walls, enhanced flood-plain storage sites, giving-room-to-the-river bed-widening and natural flood management. Our cost-effectiveness analysis is intended as a protocol to compare and choose between flood-mitigation scenarios in a quantifiable and visual manner, thereby offering better prospects of being understood by a wide audience, including citizens and city-council planners. Using techniques of data analysis combined with general river hydraulics, common-sense and upper-bound estimation, we offer an accessible check of flood-mitigation plans

Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b.

The ability of Mycobacterium tuberculosis to establish a latent infection (LTBI) in humans confounds the treatment of tuberculosis. Consequently, there is a need to discover new therapeutic agents that can kill M. tuberculosis both during active disease and LTBI. The streptomycin-dependent strain of M. tuberculosis, 18b, provides a useful tool for this purpose since upon removal of streptomycin (STR) it enters a non-replicating state that mimics latency both in vitro and in animal models. The 4.41 Mb genome sequence of M. tuberculosis 18b was determined and this revealed the strain to belong to clade 3 of the ancient ancestral lineage of the Beijing family. STR-dependence was attributable to insertion of a single cytosine in the 530 loop of the 16S rRNA and to a single amino acid insertion in the N-terminal domain of initiation factor 3. RNA-seq was used to understand the genetic programme activated upon STR-withdrawal and hence to gain insight into LTBI. This revealed reconfiguration of gene expression and metabolic pathways showing strong similarities between non-replicating 18b and M. tuberculosis residing within macrophages, and with the core stationary phase and microaerophilic responses. The findings of this investigation confirm the validity of 18b as a model for LTBI, and provide insight into both the evolution of tubercle bacilli and the functioning of the ribosome

Produção animal na Região Metropolitana de Campinas.

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Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis

and METAREACIR GroupInternational audienceBackgroundThe best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown.MethodsWe conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores).ResultsIn-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36–0.59; p 19 at baseline (OR 8.54; 95% CI 2.09–34.91; p 26 (OR 3.97; 95% CI 1.92–8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24–17.64; p = 0.022; PPV = 0.88).ConclusionsPrognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child–Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality

Compared to conventional, ecological intensive management promotes beneficial proteolytic soil microbial communities for agro-ecosystem functioning under climate change-induced rain regimes

Projected climate change and rainfall variability will affect soil microbial communities, biogeochemical cycling and agriculture. Nitrogen (N) is the most limiting nutrient in agroecosystems and its cycling and availability is highly dependent on microbial driven processes. In agroecosystems, hydrolysis of organic nitrogen (N) is an important step in controlling soil N availability. We analyzed the effect of management (ecological intensive vs. conventional intensive) on N-cycling processes and involved microbial communities under climate change-induced rain regimes. Terrestrial model ecosystems originating from agroecosystems across Europe were subjected to four different rain regimes for 263 days. Using structural equation modelling we identified direct impacts of rain regimes on N-cycling processes, whereas N-related microbial communities were more resistant. In addition to rain regimes, management indirectly affected N-cycling processes via modifications of N-related microbial community composition. Ecological intensive management promoted a beneficial N-related microbial community composition involved in N-cycling processes under climate change-induced rain regimes. Exploratory analyses identified phosphorus-associated litter properties as possible drivers for the observed management effects on N-related microbial community composition. This work provides novel insights into mechanisms controlling agro-ecosystem functioning under climate change

VaRank: a simple and powerful tool for ranking genetic variants:

Background. Most genetic disorders are caused by single nucleotide variations (SNVs) or small insertion/deletions (indels). High throughput sequencing has broadened the catalogue of human variation, including common polymorphisms, rare variations or disease causing mutations. However, identifying one variation among hundreds or thousands of others is still a complex task for biologists, geneticists and clinicians. Results. We have developed VaRank, a command-line tool for the ranking of genetic variants detected by high-throughput sequencing. VaRank scores and prioritizes variants annotated either by Alamut Batch or SnpEff. A barcode allows users to quickly view the presence/absence of variants (with homozygote/heterozygote status) in analyzed samples. VaRank supports the commonly used VCF input format for variants analysis thus allowing it to be easily integrated into NGS bioinformatics analysis pipelines. VaRank has been successfully applied to disease-gene identification as well as to molecular diagnostics setup for several hundred patients. Conclusions. VaRank is implemented in Tcl/Tk, a scripting language which is platform-independent but has been tested only on Unix environment. The source code is available under the GNU GPL, and together with sample data and detailed documentation can be downloaded from http://www.lbgi.fr/VaRank/

Study of intrinsic risk factors for falls in institutionalized elderly people

Esta pesquisa teve como objetivo identificar a presença de fatores intrínsecos que predispõem a quedas em idosos moradores em instituições de longa permanência na cidade de Goiânia (GO). Trata-se de estudo descritivo transversal realizado em seis instituições de longa permanência para idosos existentes na cidade de Goiânia. A amostra da investigação constou de 95 idosos que atenderam aos critérios de inclusão e exclusão. Utilizou-se um questionário contendo dados clínicos relacionados às condições de saúde-doença; dados cognitivos; avaliação da capacidade para as atividades básicas de vida diária e avaliação do equilíbrio e marcha. Os idosos avaliados, no geral, apresentam vários fatores de risco, apontados pela literatura, para quedas, tais como: relato de dificuldade motora em membros inferiores (90%), déficit visual (81,1%), uso de três ou mais medicamentos (59,7%), suspeita de depressão (37,9%), falta de equilíbrio em apoio unipodal (37,9%) e altura do passo anormalmente diminuída (32,6%). As informações obtidas nos permitem apontar condições determinantes que aumentam a possibilidade dos eventos queda acontecerem na amostra estudada, sinalizando à necessidade de que estratégias de promoção de saúde, prevenção de agravos e reabilitação devam ser tomadas. _________________________________________________________________________________________ ABSTRACTThe objective of this research was to identify intrinsic risk factors that predispose elderly people living in long-term institutions in the city of Goiânia (GO) to falls. The present descriptive transversal study was carried out in six long-term institutions for seniors in the city of Goiânia. The investigated sample consisted of 95 elderly that fitted the inclusion and exclusion criteria. A questionnaire was used for collecting clinical data related to health-disease conditions; cognitive data; capacity to develop basic daily life activities and equilibrium and gait. In general terms, as pointed out the literature, the examined elderly presented different fall risk factors such as: motor difficulty in lower limbs (90%), visual deficit (81,1%), use of 3 or more kinds of medicines (59,7%), suspected depression (37,9%), lack of equilibrium/unstable unipodal support (37,9%) abnormally decreased height in step (32,6%). The obtained data allow us to set indicators for the increase in falls among the studied sample, demonstrating the need for creating strategies for health promotion, prevention of injuries and rehabilitation

Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase

Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA

PURA-Related Developmental and Epileptic Encephalopathy Phenotypic and Genotypic Spectrum

Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations