National priorities for perioperative research in South Africa

Background. Perioperative research is currently unco-ordinated in South Africa (SA), with no clear research agenda.Objective. To determine the top ten national research priorities for perioperative research in SA.Methods. A Delphi technique was used to establish consensus on the top ten research priorities.Results. The top ten research priorities were as follows: (i) establishment of a national database of (a) critical care outcomes, and (b) critical care resources; (ii) a randomised controlled trial of preoperative B-type natriuretic peptide-guided medical therapy to decrease major adverse cardiac events following non-cardiac surgery; (iii) a national prospective observational study of the outcomes associated with paediatric surgical cases; (iv) a national observational study of maternal and fetal outcomes following operative delivery in SA; (v) a steppedwedge trial of an enhanced recovery after surgery programme for (a) surgery, (b) obstetrics, (c) emergency surgery, and (d) trauma surgery; (vi) a stepped-wedge trial of a surgical safety checklist on patient outcomes in SA; (vii) a prospective observational study of perioperative outcomes after surgery in district general hospitals in SA; (viii) short-course interventions to improve anaesthetic skills in rural doctors; (ix) studies of the efficacy of simulation training to improve (a) patient outcomes, (b) team dynamics, and (c) leadership; and (x) development and validation of a risk stratification tool for SA surgery based on the South African Surgical Outcomes Study (SASOS) data.Conclusions. These research priorities provide the structure for an intermediate term research agenda

A systematic review of outcomes reported inpediatric perioperative research: A report from the Pediatric Perioperative Outcomes Group

The Pediatric Perioperative Outcomes Group (PPOG) is an international collaborative of clinical investigators and clinicians within the subspecialty of pediatric anesthesiology and perioperative care which aims to use COMET (Core Outcomes Measures in Effectiveness Trials) methodology to develop core outcome sets for infants, children, and young people that are tailored to the priorities of the pediatric surgical population. Focusing on four age‐dependent patient subpopulations determined a priori for core outcome set development: (a) neonates and former preterm infants (up to 60 weeks postmenstrual age); (b) infants (>60 weeks postmenstrual age—1‐13‐<18 years), we conducted a systematic review of outcomes reported in perioperative studies that include participants within age‐dependent pediatric subpopulations. Our review of pediatric perioperative controlled trials published from 2008 to 2018 identified 724 articles reporting 3192 outcome measures. The proportion of published trials and the most frequently reported outcomes varied across predetermined age‐groups. Outcomes related to patient comfort, particularly pain and analgesic requirement, were the most frequent domain for infants, children, and adolescents. Clinical indicators, particularly cardiorespiratory or medication‐related adverse events, were the most common outcomes for neonates and infants <60 weeks and were the second most frequent domain at all other ages. Neonates and infants <60 weeks of age were significantly under‐represented in perioperative trials. Patient‐centered outcomes, healthcare utilization, and bleeding/transfusion‐related outcomes were less often reported. In most studies, outcomes were measured in the immediate perioperative period, with the duration often restricted to the postanesthesia care unit or the first 24 postoperative hours. The outcomes identified with this systematic review will be combined with patient‐centered outcomes identified through a subsequent stakeholder engagement study to arrive at a core outcome set for each age‐specific group

Filaggrin Genotype Determines Functional and Molecular Alterations in Skin of Patients with Atopic Dermatitis and Ichthyosis Vulgaris

BACKGROUND: Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD). Filaggrin (FLG) loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV), which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes. OBJECTIVE: The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected. METHODS AND FINDINGS: Patients with AD/IV (n = 43) and controls (n = 15) were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL) and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI). Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression. CONCLUSIONS: We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction

Calcium-Dependent Increases in Protein Kinase-A Activity in Mouse Retinal Ganglion Cells Are Mediated by Multiple Adenylate Cyclases

Neurons undergo long term, activity dependent changes that are mediated by activation of second messenger cascades. In particular, calcium-dependent activation of the cyclic-AMP/Protein kinase A signaling cascade has been implicated in several developmental processes including cell survival, axonal outgrowth, and axonal refinement. The biochemical link between calcium influx and the activation of the cAMP/PKA pathway is primarily mediated through adenylate cyclases. Here, dual imaging of intracellular calcium concentration and PKA activity was used to assay the role of different classes of calcium-dependent adenylate cyclases (ACs) in the activation of the cAMP/PKA pathway in retinal ganglion cells (RGCs). Surprisingly, depolarization-induced calcium-dependent PKA transients persist in barrelless mice lacking AC1, the predominant calcium-dependent adenylate cyclase in RGCs, as well as in double knockout mice lacking both AC1 and AC8. Furthermore, in a subset of RGCs, depolarization-induced PKA transients persist during the inhibition of all transmembrane adenylate cyclases. These results are consistent with the existence of a soluble adenylate cyclase that plays a role in calcium-dependent activation of the cAMP/PKA cascade in neurons

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Search for supersymmetry via associated production of charginos and neutralinos in final states with three leptons

A search for associated production of charginos and neutralinos is performed using data recorded with the D0 detector at a p (p) over bar center-of-mass energy of 1.96 TeV at the Fermilab Tevatron Collider. This analysis considers final states with missing transverse energy and three charged leptons, of which at least two are electrons or muons. No evidence for supersymmetry is found in a data set corresponding to an integrated luminosity of 320 pb(-1). Limits on the product of the production cross section and leptonic branching fraction are set. For the minimal supergravity model, a chargino lower mass limit of 117 GeV at the 95% C.L. is derived in regions of parameter space with enhanced leptonic branching fractions

Caballero Bonald : 'José Agustín Goytisolo ansiaba ser seductor'

Publicat a ABC

Search for doubly charged Higgs boson pair production in the decay to mu(+)mu(+)mu(-)mu(-) in p(p)over-bar collisions at root s=1.96 TeV

A search for pair production of doubly charged Higgs bosons in the process p (p) over bar -->H++H---->mu(+)mu(+)mu(-)mu(-) is performed with the D0 run II detector at the Fermilab Tevatron. The analysis is based on a sample of inclusive dimuon data collected at an energy of roots=1.96 TeV, corresponding to an integrated luminosity of 113 pb(-1). In the absence of a signal, 95% confidence level mass limits of M(H-L(+/-+/-))>118.4 GeV/c(2) and M(H-R(+/-+/-))>98.2 GeV/c(2) are set for left-handed and right-handed doubly charged Higgs bosons, respectively, assuming 100% branching into muon pairs

Measurement of sigma(p(p)over-bar -> Z)center dot Br(Z ->tau tau) at root s=1.96 TeV (vol 71, art no. 072004, 2005)

A change in estimated integrated luminosity (from 226 pb$^{-1} to 257 pb$^{-1}$leads to a corrected value for${\sigma (p \bar p \to Z) \cdot}$Br${(Z \to \tau \tau)}$of$209\pm13(stat.)\pm16(syst.)\pm13(lum) pb