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Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya. We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1-14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2-14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2-0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1-8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4-3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2-3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5-4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home. Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness.

BackgroundThe projected impact and cost-effectiveness of rotavirus vaccination are important for supporting rotavirus vaccine introduction in Africa, where limited health intervention funds are available MethodsHospital records, health utilization surveys, verbal autopsy data, and surveillance data on diarrheal disease were used to determine rotavirus-specific rates of hospitalization, clinic visits, and deaths due to diarrhea among children <5 years of age in Nyanza Province, Kenya. Rates were extrapolated nationally with use of province-specific data on diarrheal illness. Direct medical costs were estimated using record review and World Health Organization estimates. Household costs were collected through parental interviews. The impact of vaccination on health burden and on the cost-effectiveness per disability-adjusted life-year and lives saved were calculated ResultsAnnually in Kenya, rotavirus infection causes 19% of hospitalizations and 16% of clinic visits for diarrhea among children <5 years of age and causes 4471 deaths, 8781 hospitalizations, and 1,443,883 clinic visits. Nationally, rotavirus disease costs the health care system $10.8 million annually. Routine vaccination with a 2-dose rotavirus vaccination series would avert 2467 deaths (55%), 5724 hospitalizations (65%), and 852,589 clinic visits (59%) and would save 58 disability-adjusted life-years per 1000 children annually. At $3 per series, a program would cost $2.1 million in medical costs annually; the break-even price is $2.07 per series ConclusionsA rotavirus vaccination program would reduce the substantial burden of rotavirus disease and the economic burden in Kenya

Current literature suggests an increased attentional bias toward food stimuli in eating-disordered individuals compared to healthy controls. In line with these research efforts, the present study aims to investigate the processing of food stimuli (enriched by emotional stimuli) between patients diagnosed for anorexia nervosa (AN) and healthy controls by means of electroencephalography. Twenty-two female adolescents (eleven AN patients vs. eleven healthy controls) were investigated. Positive event-related potentials “P300” and “late positive potential” (LPP) reflecting attentional processing (caused by motivationally relevant stimuli) were investigated during passive viewing of the food cue picture stream. This method was used for the first time in a sample of individuals with AN. As a main result, AN patients exhibited a higher amount of attentional bias in P300 and LPP, while watching food stimuli. Moreover, AN patients rated food stimuli as less pleasant. For a conclusion, there is substantial evidence pointing to an abnormal attentional brain reactivity to food pictures in AN. Therefore, food stimuli seem to be more motivationally relevant for AN patients than for healthy controls. By broadening existing knowledge, these findings might bear some implications for the treatment for AN. However, further research is recommended in order to confirm the results coming from rather limited data.

Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child's health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06-2.57), underweight (aOR = 2.08, 95% CI: 1.34-3.22), or wasted (aOR = 2.04, 95% CI: 1.21-3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment. Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed.

To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0-11 months old (aOR = 5.29, 95% CI 3.14-8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91-3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease.

We describe the construction and characterization of a genomically recoded organism (GRO). We replaced all known UAG stop codons in Escherichia coli MG1655 with synonymous UAA codons, which permitted the deletion of release factor 1 and reassignment of UAG translation function. This GRO exhibited improved properties for incorporation of nonstandard amino acids that expand the chemical diversity of proteins in vivo. The GRO also exhibited increased resistance to T7 bacteriophage, demonstrating that new genetic codes could enable increased viral resistance.

We demonstrate, to our knowledge, the first bright circularly polarized high-harmonic beams in the soft X-ray region of the electromagnetic spectrum, and use them to implement X-ray magnetic circular dichroism measurements in a tabletop-scale setup. Using counterrotating circularly polarized laser fields at 1.3 and 0.79 μm, we generate circularly polarized harmonics with photon energies exceeding 160 eV. The harmonic spectra emerge as a sequence of closely spaced pairs of left and right circularly polarized peaks, with energies determined by conservation of energy and spin angular momentum. We explain the single-atom and macroscopic physics by identifying the dominant electron quantum trajectories and optimal phase-matching conditions. The first advanced phase-matched propagation simulations for circularly polarized harmonics reveal the influence of the finite phase-matching temporal window on the spectrum, as well as the unique polarization-shaped attosecond pulse train. Finally, we use, to our knowledge, the first tabletop X-ray magnetic circular dichroism measurements at theN4,5 absorption edges of Gd to validate the high degree of circularity, brightness, and stability of this light source. These results demonstrate the feasibility of manipulating the polarization, spectrum, and temporal shape of high harmonics in the soft X-ray region by manipulating the driving laser waveform.

The recent explosion of ‘big data’ has ushered in a new era of artificial intelligence (AI) algorithms in every sphere of technological activity, including medicine, and in particular radiology. However, the recent success of AI in certain flagship applications has, to some extent, masked decades-long advances in computational technology development for medical image analysis. In this article, we provide an overview of the history of AI methods for radiological image analysis in order to provide a context for the latest developments. We review the functioning, strengths and limitations of more classical methods as well as of the more recent deep learning techniques. We discuss the unique characteristics of medical data and medical science that set medicine apart from other technological domains in order to highlight not only the potential of AI in radiology but also the very real and often overlooked constraints that may limit the applicability of certain AI methods. Finally, we provide a comprehensive perspective on the potential impact of AI on radiology and on how to evaluate it not only from a technical point of view but also from a clinical one, so that patients can ultimately benefit from it.Key Points• Artificial intelligence (AI) research in medical imaging has a long history• The functioning, strengths and limitations of more classical AI methods is reviewed, together with that of more recent deep learning methods.• A perspective is provided on the potential impact of AI on radiology and on its evaluation from both technical and clinical points of view.

Background Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds. Methods Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5 × 7 cm (35 cm 2 ) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for ≥ 12 weeks. Results Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9 years (range 4–8 years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated ≥ 50% wound healing compared to baseline by investigator global assessment. No sites with ≥ 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing ( p  < 0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9 years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up. Conclusions Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming. Trial registration ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379