Extending a result of Ryan on weakly compact operators

Peer reviewedPublisher PD

Management of severe paediatric malaria in resource-limited settings.

Over 90% of the worlds severe and fatal Plasmodium falciparum malaria is estimated to affect young children in sub-Sahara Africa, where it remains a common cause of hospital admission and inpatient mortality. Few children will ever be managed on high dependency or intensive care units and, therefore, rely on simple supportive treatments and parenteral anti-malarials. There has been some progress on defining best practice for antimalarial treatment with the publication of the AQUAMAT trial in 2010, involving 5,425 children at 11 centres across 9 African countries, showing that in artesunate-treated children, the relative risk of death was 22.5% (95% confidence interval (CI) 8.1 to 36.9) lower than in those receiving quinine. Human trials of supportive therapies carried out on the basis of pathophysiology studies, have so far made little progress on reducing mortality; despite appearing to reduce morbidity endpoints, more often than not they have led to an excess of adverse outcomes. This review highlights the spectrum of complications in African children with severe malaria, the therapeutic challenges of managing these in resource-poor settings and examines in-depth the results from clinical trials with a view to identifying the treatment priorities and a future research agenda

Hsp-90 and the biology of nematodes

BACKGROUND: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA). Here we surveyed 24 different free-living or parasitic nematodes with the aim of determining whether C. elegans Hsp-90 was the exception or the norm amongst the nematodes. We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints.<BR/>RESULTS: We show that GA-binding is associated with life history: free-living nematodes and those parasitic species with free-living larval stages failed to bind GA. In contrast, obligate parasites and those worms in which the free-living stage in the environment is enclosed within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences from fifteen nematode species to determine whether nematode hsp-90s have undergone adaptive evolution that influences GA-binding. Our data provide evidence of rapid diversifying selection in the evolution of the hsp-90 gene along three separate lineages, and identified a number of residues showing significant evidence of adaptive evolution. However, we were unable to prove that the selection observed is correlated with the ability to bind geldanamycin or not.<BR/>CONCLUSION: Hsp-90 is a multi-functional protein and the rapid evolution of the hsp-90 gene presumably correlates with other key cellular functions. Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin

Children with severe malnutrition: can those at highest risk of death be identified with the WHO protocol?

Background With strict adherence to international recommended treatment guidelines, the case fatality for severe malnutrition ought to be less than 5%. In African hospitals, fatality rates of 20% are common and are often attributed to poor training and faulty case management. Improving outcome will depend upon the identification of those at greatest risk and targeting limited health resources. We retrospectively examined the major risk factors associated with early (<48 h) and late in-hospital death in children with severe malnutrition with the aim of identifying admission features that could distinguish a high-risk group in relation to the World Health Organization (WHO) guidelines. Methods and Findings Of 920 children in the study, 176 (19%) died, with 59 (33%) deaths occurring within 48 h of admission. Bacteraemia complicated 27% of all deaths: 52% died before 48 h despite 85% in vitro antibiotic susceptibility of cultured organisms. The sensitivity, specificity, and likelihood ratio of the WHO-recommended “danger signs” (lethargy, hypothermia, or hypoglycaemia) to predict early mortality was 52%, 84%, and 3.4% (95% confidence interval [CI] = 2.2 to 5.1), respectively. In addition, four bedside features were associated with early case fatality: bradycardia, capillary refill time greater than 2 s, weak pulse volume, and impaired consciousness level; the presence of two or more features was associated with an odds ratio of 9.6 (95% CI = 4.8 to 19) for early fatality (p < 0.0001). Conversely, the group of children without any of these seven features, or signs of dehydration, severe acidosis, or electrolyte derangements, had a low fatality (7%). Conclusions Formal assessment of these features as emergency signs to improve triage and to rationalize manpower resources toward the high-risk groups is required. In addition, basic clinical research is necessary to identify and test appropriate supportive treatments

Oral rehydration of malnourished children with diarrhoea and dehydration: A systematic review [version 1; referees: 1 approved, 1 approved with reservations]

Background: Diarrhoea complicates over half of admissions to hospital with severe acute malnutrition (SAM). World Health Organization (WHO) guidelines for the management of dehydration recommend the use of oral rehydration with ReSoMal (an oral rehydration solution (ORS) for SAM), which has lower sodium (45mmols/l) and higher potassium (20mmols/l) content than standard ORS. The composition of ReSoMal was designed specifically to address theoretical risks of sodium overload and potential under-treatment of severe hypokalaemia with rehydration using standard ORS. In African children, severe hyponatraemia at admission is a major risk factor for poor outcome in children with SAM complicated by diarrhoea. We therefore reviewed the evidence for oral rehydration therapy in children with SAM. Methods: We conducted a systematic review of randomised controlled trials (RCTs) on 18th July 2017 comparing different oral rehydration solutions in severely malnourished children with diarrhoea and dehydration, using standard search terms. The author assessed papers for inclusion. The primary endpoint was frequency of hyponatraemia during rehydration. Results: Six RCTs were identified, all published in English and conducted in low resource settings in Asia. A range of ORS were evaluated in these studies, including standard ORS, hypo-osmolar ORS and ReSoMal. Hyponatraemia was observed in two trials evaluating ReSoMal, three children developed severe hyponatraemia with one experiencing convulsions. Hypo-osmolar ORS was found to have benefits in time to rehydration, reduction of stool output and duration of diarrhoea. No trials reported over-hydration or fatalities. Conclusions: Current WHO guidelines strongly recommend the use of ReSoMal based on low quality of evidence. Studies indicate a significant risk of hyponatraemia on ReSoMal in Asian children, none have been conducted in Africa, where SAM mortality remains high. Further research should be conducted in Africa to evaluate optimal ORS for children with SAM and to generate evidence based, practical guidelines

Synthetic magnetism for photon fluids

We develop a theory of artificial gauge fields in photon fluids for the cases of both second-order and third-order optical nonlinearities. This applies to weak excitations in the presence of pump fields carrying orbital angular momentum, and is thus a type of Bogoliubov theory. The resulting artificial gauge fields experienced by the weak excitations are an interesting generalization of previous cases and reflect the PT-symmetry properties of the underlying non-Hermitian Hamiltonian. We illustrate the observable consequences of the resulting synthetic magnetic fields for examples involving both second-order and third-order nonlinearities