Social welfare [law] advice provision during the pandemic in England and Wales: a conceptual framework

An ambitious reform programme in the UK to digitalize the justice system has been underway since 2016. The report on Digitisation and accessing justice in the community (based on the Digitalisation Welfare Advice Survey), on how prepared advice providers were for digital assistance for welfare benefits, found that organisations were unable to meet the demand for services across all levels of social welfare law, and that there is a high demand for digital assistance. This was just before the pandemic. This paper explores the technical capability of the advice sector to provide remote social welfare delivery during the pandemic. It is based on a Pandemic Welfare Advice survey to help understand how advice providers have been working during the first seven months of the pandemic in 2020 and how the migration to remote advice delivery has changed their services and impacted their clients. A conceptual framework of needs is offered as a lens though which to think about the new sets of demands on advisers and clients

A malaria parasite subtilisin propeptide-like protein is a potent inhibitor of the egress protease SUB1.

Subtilisin-like serine peptidases (subtilases) play important roles in the life cycle of many organisms, including the protozoan parasites that are the causative agent of malaria, Plasmodium spp. As with other peptidases, subtilase proteolytic activity has to be tightly regulated in order to prevent potentially deleterious uncontrolled protein degradation. Maturation of most subtilases requires the presence of an N-terminal propeptide that facilitates folding of the catalytic domain. Following its proteolytic cleavage, the propeptide acts as a transient, tightly bound inhibitor until its eventual complete removal to generate active protease. Here we report the identification of a stand-alone malaria parasite propeptide-like protein, called SUB1-ProM, encoded by a conserved gene that lies in a highly syntenic locus adjacent to three of the four subtilisin-like genes in the Plasmodium genome. Template-based modelling and ab initio structure prediction showed that the SUB1-ProM core structure is most similar to the X-ray crystal structure of the propeptide of SUB1, an essential parasite subtilase that is discharged into the parasitophorous vacuole (PV) to trigger parasite release (egress) from infected host cells. Recombinant Plasmodium falciparum SUB1-ProM was found to be a fast-binding, potent inhibitor of P. falciparum SUB1, but not of the only other essential blood-stage parasite subtilase, SUB2, or of other proteases examined. Mass-spectrometry and immunofluorescence showed that SUB1-ProM is expressed in the PV of blood stage P. falciparum, where it may act as an endogenous inhibitor to regulate SUB1 activity in the parasite

Measurement of gut permeability using fluorescent tracer agent technology

Abstract The healthy gut restricts macromolecular and bacterial movement across tight junctions, while increased intestinal permeability accompanies many intestinal disorders. Dual sugar absorption tests, which measure intestinal permeability in humans, present challenges. Therefore, we asked if enterally administered fluorescent tracers could ascertain mucosal integrity, because transcutaneous measurement of differentially absorbed molecules could enable specimen-free evaluation of permeability. We induced small bowel injury in rats using high- (15 mg/kg), intermediate- (10 mg/kg), and low- (5 mg/kg) dose indomethacin. Then, we compared urinary ratios of enterally administered fluorescent tracers MB-402 and MB-301 to urinary ratios of sugar tracers lactulose and rhamnose. We also tested the ability of transcutaneous sensors to measure the ratios of absorbed fluorophores. Urinary fluorophore and sugar ratios reflect gut injury in an indomethacin dose dependent manner. The fluorophores generated smooth curvilinear ratio trajectories with wide dynamic ranges. The more chaotic sugar ratios had narrower dynamic ranges. Fluorophore ratios measured through the skin distinguished indomethacin-challenged from same day control rats. Enterally administered fluorophores can identify intestinal injury in a rat model. Fluorophore ratios are measureable through the skin, obviating drawbacks of dual sugar absorption tests. Pending validation, this technology should be considered for human use

Nosocomial nontyphoidal salmonellosis after antineoplastic chemotherapy: reactivation of asymptomatic colonization?

An increased frequency of nontyphoidal salmonellosis is well established in cancer patients, but it is unclear whether this represents increased susceptibility to exogenous infection or opportunistic, endogenous reactivation of asymptomatic carriage. In a retrospective study, a simple case definition was used to identify the probable presence of reactivation salmonellosis in five cancer patients between 1996 and 2002. Reactivation salmonellosis was defined as the development of nosocomial diarrhea >72h after admission and following the administration of antineoplastic chemotherapy in an HIV-seronegative cancer patient who was asymptomatic on admission, in the absence of epidemiological evidence of a nosocomial outbreak. Primary salmonellosis associated with unrecognized nosocomial transmission or community acquisition and an unusually prolonged incubation period could not entirely be ruled out. During the same time period, another opportunistic infection, Pneumocystis pneumonia, was diagnosed in six cancer patients. Presumably, asymptomatic intestinal Salmonella colonization was converted to invasive infection by chemotherapy-associated intestinal mucosal damage and altered innate immune mechanisms. According to published guidelines, stool specimens from patients hospitalized for longer than 72h should be rejected unless the patient is neutropenic or ≧65 years old with significant comorbidity. However, in this study neutropenia was present in only one patient, and four patients were <65 years old. Guidelines should thus be revised in order not to reject stool culture specimens from such patients. In cancer patients, nosocomial salmonellosis can occur as a chemotherapy-triggered opportunistic reactivation infection that may be similar in frequency to Pneumocystis pneumoni

Escherichia coli O157 Exposure in Wyoming and Seattle: Serologic Evidence of Rural Risk

We tested the hypothesis that rural populations have increased exposure to Escherichia coli O157:H7. We measured circulating antibodies against the O157 lipopolysaccharide in rural Wyoming residents and in blood donors from Casper, Wyoming, and Seattle, Washington, by enzyme immunoassay (EIA). EIA readings were compared by analysis of variance and the least squares difference multiple comparison procedure. Rural Wyoming residents had higher antibody levels to O157 LPS than did Casper donors, who, in turn, had higher levels than did Seattle donors (respective least squares means: 0.356, 0.328, and 0.310; p<0.05, Seattle vs. Casper, p<0.001, rural Wyoming vs. either city). Lower age was significantly correlated with EIA scores; gender; and, in rural Wyoming, history of bloody diarrhea, town, duration of residence, and use of nontreated water at home were not significantly correlated. These data suggest that rural populations are more exposed to E. coli O157:H7 than urban populations

Generic 3D Representation via Pose Estimation and Matching

Though a large body of computer vision research has investigated developing generic semantic representations, efforts towards developing a similar representation for 3D has been limited. In this paper, we learn a generic 3D representation through solving a set of foundational proxy 3D tasks: object-centric camera pose estimation and wide baseline feature matching. Our method is based upon the premise that by providing supervision over a set of carefully selected foundational tasks, generalization to novel tasks and abstraction capabilities can be achieved. We empirically show that the internal representation of a multi-task ConvNet trained to solve the above core problems generalizes to novel 3D tasks (e.g., scene layout estimation, object pose estimation, surface normal estimation) without the need for fine-tuning and shows traits of abstraction abilities (e.g., cross-modality pose estimation). In the context of the core supervised tasks, we demonstrate our representation achieves state-of-the-art wide baseline feature matching results without requiring apriori rectification (unlike SIFT and the majority of learned features). We also show 6DOF camera pose estimation given a pair local image patches. The accuracy of both supervised tasks come comparable to humans. Finally, we contribute a large-scale dataset composed of object-centric street view scenes along with point correspondences and camera pose information, and conclude with a discussion on the learned representation and open research questions.Comment: Published in ECCV16. See the project website http://3drepresentation.stanford.edu/ and dataset website https://github.com/amir32002/3D_Street_Vie

Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis

Background Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. Methods and results Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using culture-independent molecular techniques and reported α and β-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). Conclusions Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC

Robust high-dimensional precision matrix estimation

The dependency structure of multivariate data can be analyzed using the covariance matrix $\Sigma$. In many fields the precision matrix $\Sigma^{-1}$ is even more informative. As the sample covariance estimator is singular in high-dimensions, it cannot be used to obtain a precision matrix estimator. A popular high-dimensional estimator is the graphical lasso, but it lacks robustness. We consider the high-dimensional independent contamination model. Here, even a small percentage of contaminated cells in the data matrix may lead to a high percentage of contaminated rows. Downweighting entire observations, which is done by traditional robust procedures, would then results in a loss of information. In this paper, we formally prove that replacing the sample covariance matrix in the graphical lasso with an elementwise robust covariance matrix leads to an elementwise robust, sparse precision matrix estimator computable in high-dimensions. Examples of such elementwise robust covariance estimators are given. The final precision matrix estimator is positive definite, has a high breakdown point under elementwise contamination and can be computed fast