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Terrestrial Gamma‐ray Flashes (TGFs) are ten‐to‐hundreds of microsecond bursts of gamma‐rays produced when electrons in strong electric fields in thunderclouds are accelerated to relativistic energies. Space instruments have observed TGFs with source photon brightness down to ∼1017–1016. Based on space and aircraft observations, TGFs have been considered rare phenomena produced in association with very few lightning discharges. Space observations associated with lightning ground observations in the radio band have indicated that there exists a population of dimmer TGFs. Here we show observations of TGFs from aircraft altitude that were not detected by a space instrument viewing the same area. The TGFs were found through Monte Carlo modeling to be associated with 1015–1012 photons at source, which is several orders of magnitude below what can be seen from space. Our results suggest that there exists a significant population of TGFs that are too weak to be observed from space. Plain Language Summary: Terrestrial Gamma‐ray Flashes (TGFs) are short bursts of gamma‐rays produced in the strong electric fields in thunderclouds. Based on space and aircraft observations, TGFs have been considered a rare phenomena. In this paper, we present observations of TGFs from an aircraft campaign that were not detected by a space instrument viewing the same area. Our results reveal that these TGFs were too weak to be observed from space, indicating a significant population of TGFs that are undetectable by space instruments. Key Points: The ALOFT flight campaign detected six TGFs within a few minutes during an ISS overpass, and none were detected by the ASIM instrumentWe show that there must be a population of TGFs that are too weak to be observed from spaceThe fluence at 15 km of this population is 2–5 orders of magnitude lower than the TGFs observed from space [ABSTRACT FROM AUTHOR]

Summary: An important subgroup of people who inject drugs (PWID) receiving opioid agonist therapy (OAT) cannot be treated in the setting of a hepatology centre and would not regularly ingest their medication when handed to them for self‐administration. Our hypothesis was that chronic hepatitis C in these patients could be ideally managed if modern, interferon‐free regimens were administered together with OAT under direct observation of a physician or nurse at a low‐threshold facility. In this open‐label, noninterventional, proof‐of‐concept study (ClinicalTrials.gov number, NCT02638233), 40 PWID at risk of nonadherence to direct‐acting antivirals (DAA) and previously untreated chronic hepatitis C virus genotype 1 infection without cirrhosis were treated with ledipasvir/sofosbuvir for 8 weeks. Patients received antiviral treatment together with OAT under direct observation of a physician or nurse at a low‐threshold facility. By following the concept of directly observed therapy, excellent adherence to antiviral therapy was achieved as follows: only 0.16% (95% CI: 0.03‐0.47) of scheduled dates for ingestion of the antiviral therapy in combination with OAT were missed by the 40 patients. The rate of sustained virological response 12 weeks after end of therapy was 100% (95% CI: 91.2‐100.0). Between week 12 and week 24 of follow‐up reinfections were recorded in 2 of 40 patients (5%). Directly observed therapy of chronic hepatitis C is highly effective in PWID at risk of nonadherence to DAA. By this new concept, a group of difficult‐to‐treat patients can be cured, who could not have been treated in settings of studies published so far. [ABSTRACT FROM AUTHOR]

Background: Clinico-pathological correlation of thyroid nodules is not routinely performed as until recently there was no objective classification system for reporting thyroid nodules on ultrasound. We compared the Thyroid Imaging Reporting and Data System (TIRADS) of classifying thyroid nodules on ultrasound with the findings on fine-needle aspiration cytology (FNAC) reported using the Bethesda System. Methods: A retrospective analysis of 100 consecutive cases over 1 year (Jan-Dec 2015) was performed comparing single-surgeon-performed bedside thyroid nodule ultrasound findings based on the TIRADS classification to the FNAC report based on the Bethesda Classification. TIRADS 1 (normal thyroid gland) and biopsy-proven malignancy referred by other clinicians were excluded. Benign-appearing nodules were reported as TIRADS 2 and 3. Indeterminate or suspected follicular lesions were reported as TIRADS 4, and malignant-appearing nodules were classified as TIRADS 5 during surgeon-performed bedside ultrasound. All the nodules were subjected to ultrasound-guided FNAC, and TIRADS findings were compared to Bethesda FNAC Classification. Results: Of the 100 cases, 74 were considered benign or probably benign, 20 were suspicious for malignancy, and 6 were indeterminate on ultrasound. Overall concordance rate with FNAC was 83% with sensitivity and specificity of 70.6 and 90.4%, respectively. The negative predictive value was 93.8%. Conclusion: It is essential for clinicians performing bedside ultrasound thyroid and guided FNAC to document their sonographic impression of the nodule in an objective fashion using the TIRADS classification and correlate with the gold standard cytology to improve their learning curve and audit their results. [ABSTRACT FROM AUTHOR]

Tungsten (W), a promising candidate as divertor plasma facing material in magnetic fusion devices, is anticipated to promptly redeposit when sputtered or evaporated from surface due to its small ionization energy and long gyro radius. Using an artificial factor for the reaction cross sections, effects of ionization lengths to the re-deposition rate was studied by a newly developed particle-in-cell code. Treating numbers of particles in a super particle, electric charge, and mass as particle variables in the code, a special scheme for ionization and recombination was developed and used for the calculation. Simulations on W test particles with imaginary properties (neglecting the electric force) revealed the effects of ejection angles. Simulations with secondary electrons from surface showed that the sheath potential is weakened and the re-deposition rate becomes small. It was found that the multi-ionization as well as the ionization mean-free-path influences the re-deposition rate in both simulations. (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The detached plasmas due to the volume recombination are studied by using one-dimensional (1D) scrape-off-layer-divertor (SOL-DIV) plasma fluid code with virtual divertor (VD) model. By introducing the anisotropic ion temperature, the parallel momentum transport equation becomes the first-order differential and the Mach number at the sheath entrance is determined self-consistently by the upstream condition. The total particle flux at the divertor plates and the flux amplification factors are shown as functions of the plasma density at the stagnation point and the dependence of these parameters on the heat flux from the core plasma, radial width of the flux tube in the divetor region and the strength of the impurity radiation is investigated. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Background Within the context of paediatric chronic pain, parental attitudes are of particular importance given that they have the potential to impact on how parents respond to their child. The current study was designed to assess whether parental attitudes, such as parental confidence and beliefs in their child's ability to function in spite of pain, and parental catastrophising about their child's pain, are associated with parental pain-related behaviours known to be associated with poor child outcomes, such as protectiveness and high levels of monitoring. Methods Participants were 138 child-parent dyads recruited from a tertiary chronic pain clinic. Patients were aged 8- to 17-years. Prior to the initial clinic appointment, parents completed validated measures of parental pain catastrophising and parental responses to their child's pain. Patients completed measures of functional disability and pain intensity. Results Parents who reported lower confidence in their child's ability to cope with the pain engaged in significantly more protective, monitoring and distracting behaviours, even when controlling for the child's recent level of functioning. They also took more days off work due to their child's pain. Parents who catastrophised more about their child's pain engaged in significantly more protective and monitoring behaviours, even when controlling for the child's recent level of functioning. Conclusions Parental behaviours in response to their child's pain are significantly related to parental confidence in their child's coping and parental pain-related catastrophising. Clinical interventions may benefit from addressing parental attitudes, especially their confidence in their child's ability to function. [ABSTRACT FROM AUTHOR]

Patients with hepatitis B e antigen ( HBe Ag)-positive chronic hepatitis B ( CHB) have suppressed TLR2 expression, function and cytokine production. The aim of this study was to explore the importance of hepatitis B virus ( HBV) genotype in innate immune responses and investigate whether Toll-like receptor ( TLR) expression/function has potential roles as predictive biomarkers of successful therapy with pegylated interferon ( Peg- IFN) therapy of HBe Ag seroconversion in HBe Ag-positive patients. We showed that as early as 4 weeks after initiation of Peg- IFN, future HBe Ag seroconverters had significantly elevated levels of TLR2 expression on monocytes. TLR2-associated IL-6 production at baseline and week 4 of therapy and TLR4 IL-6 production at week 4 were also markedly elevated in HBe Ag seroconverters. HBV genotype also influenced treatment response, with genotypes A and B more likely to seroconvert than D. We were able to demonstrate that these differences were due in part to the interaction of the specific HBe Ag proteins with TLR pathway adaptor molecules, and these interactions were genotype dependent. HBe Ag-mediated modulation of TLR signalling was also observed in Huh7 cells, following stimulation with Pam3 Cys. Importantly, the addition of IFN-α to TLR2-stimulated cells cotransfected with an HBe Ag expression plasmid reversed HBe Ag-mediated suppression of hepatocytes. These findings demonstrate that patients with an activated inflammatory response are much more likely to respond to IFN therapy, with TLR responses showing promise as potential biomarkers of HBe Ag seroconversion in this setting. Furthermore, our findings suggest there is differential genotype-specific HBe Ag suppression of innate signalling pathways which may account for some of the clinical differences observed across the CHB spectrum. [ABSTRACT FROM AUTHOR]

An Illumina Infinium SNP genotyping array was constructed for European white oaks. Six individuals of Quercus petraea and Q. robur were considered for SNP discovery using both previously obtained Sanger sequences across 676 gene regions (1371 in vitro SNPs) and Roche 454 technology sequences from 5112 contigs (6542 putative in silico SNPs). The 7913 SNPs were genotyped across the six parental individuals, full-sib progenies (one within each species and two interspecific crosses between Q. petraea and Q. robur) and three natural populations from south-western France that included two additional interfertile white oak species ( Q. pubescens and Q. pyrenaica). The genotyping success rate in mapping populations was 80.4% overall and 72.4% for polymorphic SNPs. In natural populations, these figures were lower (54.8% and 51.9%, respectively). Illumina genotype clusters with compression (shift of clusters on the normalized x-axis) were detected in ~25% of the successfully genotyped SNPs and may be due to the presence of paralogues. Compressed clusters were significantly more frequent for SNPs showing a priori incorrect Illumina genotypes, suggesting that they should be considered with caution or discarded. Altogether, these results show a high experimental error rate for the Infinium array (between 15% and 20% of SNPs potentially unreliable and 10% when excluding all compressed clusters), and recommendations are proposed when applying this type of high-throughput technique. Finally, results on diversity levels and shared polymorphisms across targeted white oaks and more distant species of the Quercus genus are discussed, and perspectives for future comparative studies are proposed. [ABSTRACT FROM AUTHOR]

Using next-generation sequencing, we developed the first whole-genome resources for two hybridizing Nothofagus species of the Patagonian forests that crucially lack genomic data, despite their ecological and industrial value. A de novo assembly strategy combining base quality control and optimization of the putative chloroplast gene map yielded ~32 000 contigs from 43% of the reads produced. With 12.5% of assembled reads, we covered ~96% of the chloroplast genome and ~70% of the mitochondrial gene content, providing functional and structural annotations for 112 and 52 genes, respectively. Functional annotation was possible on 15% of the contigs, with ~1750 potentially novel nuclear genes identified for Nothofagus species. We estimated that the new resources (13.41 Mb in total) included ~4000 gene regions representing ~6.5% of the expected genic partition of the genome, the remaining contigs potentially being nongenic DNA. A high-quality single nucleotide polymorphisms resource was developed by comparing various filtering methods, and preliminary results indicate a strong conservation of cp DNA genomes in contrast to numerous exclusive nuclear polymorphisms in both species. Finally, we characterized 2274 potential simple sequence repeat ( SSR) loci, designed primers for 769 of them and validated nine of 29 loci in 42 individuals per species. Nothofagus obliqua had more alleles (4.89) on average than N. nervosa (2.89), 8 SSRs were efficient to discriminate species, and three were successfully transferred in three other Nothofagus species. These resources will greatly help for future inferences of demographic, adaptive and hybridizing events in Nothofagus species, and for conserving and managing natural populations. [ABSTRACT FROM AUTHOR]

Loci considered to be under selection are generally avoided in attempts to infer past demographic processes as they do not fit neutral model assumptions. However, opportunities to better reconstruct some aspects of past demography might thus be missed. Here we examined genetic differentiation between two sympatric European oak species with contrasting ecological dynamics ( Quercus robur and Quercus petraea) with both outlier (i.e. loci possibly affected by divergent selection between species or by hitchhiking effects with genomic regions under selection) and nonoutlier loci. We sampled 855 individuals in six mixed forests in France and genotyped them with a set of 262 SNPs enriched with markers showing high interspecific differentiation, resulting in accurate species delimitation. We identified between 13 and 74 interspecific outlier loci, depending on the coalescent simulation models and parameters used. Greater genetic diversity was predicted in Q. petraea (a late-successional species) than in Q. robur (an early successional species) as introgression should theoretically occur predominantly from the resident species to the invading species. Remarkably, this prediction was verified with outlier loci but not with nonoutlier loci. We suggest that the lower effective interspecific gene flow at loci showing high interspecific divergence has better preserved the signal of past asymmetric introgression towards Q. petraea caused by the species' contrasting dynamics. Using markers under selection to reconstruct past demographic processes could therefore have broader potential than generally recognized. [ABSTRACT FROM AUTHOR]

Background The prevention and treatment of liver disease associated with cystic fibrosis remain a significant unresolved problem. Aim To assess the long-term effects of continuous ursodeoxycholic acid ( UDCA) therapy in cystic fibrosis patients with constantly elevated serum liver enzymes. Methods The primary endpoint was the incidence of overt liver disease. Between 1989 and 2005, UDCA treatment was started in 98 subjects from a cohort of 382 cystic fibrosis patients. These subjects were compared with a historic control group of 352 subjects who attended our centre between 1975 and 1989 before UDCA became standard treatment. For the long-term comparison of liver function and lung function tests, a group of 98 matched contemporary cystic fibrosis patients were compared with the 98 subjects treated with UDCA. Results Overt liver disease developed in only one of the 382 patients who was treated with UDCA for increased serum liver enzymes compared with nine patients in the historic control group ( P < 0.05). Serum liver enzyme levels declined in most patients receiving UDCA treatment during the 17-year follow-up (87/98, P < 0.05). No difference was seen in lung function between subjects with cystic fibrosis-related liver disease and the matched controls. Conclusions Regular and systematic screening for liver involvement enables early introduction of UDCA therapy in affected cystic fibrosis patients, reduces the development of severe liver disease and leads to a significant and persistent improvement in serum liver tests, without impairing long-term pulmonary outcome. [ABSTRACT FROM AUTHOR]

Summary. Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR ( n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment ( n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels ( n = 4) or missing HCV RNA at the 24-week follow-up visit ( n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment. [ABSTRACT FROM AUTHOR]

Objectives: Heart fatty acid-binding protein (h-FABP) and ischemia-modified albumin (IMA) have recently been evaluated, but to the best of our knowledge, no study has reported an analysis of these two markers for the detection of early myocardial infarction and myocardial ischemia in a large cohort of consecutive patients presenting to an emergency department (ED). This study evaluates the diagnostic accuracy and the clinical utility of h-FABP and IMA for non-ST-segment elevation acute coronary syndrome (ACS) diagnosis in the first hour of management in an ED. Methods: In a prospective 11-month study, 677 patients admitted to the ED with chest pain and suspected non-ST-segment elevation ACS were enrolled. On presentation, blood samples were obtained for the measurement of the biomarkers h-FABP (immunodetection with CardioDetect) and IMA (albumin cobalt-binding test). Two physicians, blinded to the results of the markers, independently categorized patients as having or not having non-ST-segment elevation ACS. Results: Of the 677 patients who were prospectively recruited, non-ST-segment elevation ACS was diagnosed in 185 (27.3%). While IMA was not predictive of the ACS diagnosis (odds ratio [OR] = 1.23; 95% CI = 0.87 to 1.81), h-FABP was predictive of ACS diagnosis (OR = 4.65; 95% CI = 2.39 to 9.04) with specificity at 96.8% (95% CI = 95.4% to 98.1%) and sensitivity at 13.5% (95% CI = 10.9% to 16.1%). However, h-FABP did not add significant additional information to a predictive model that included the usual diagnostic tools for non-ST-elevation ACS management (p = 0.40). Conclusions: In this study on a large cohort of patients admitted to an ED for chest pain, IMA and h-FABP did not provide valuable information for ACS diagnosis. ACADEMIC EMERGENCY MEDICINE 2010; 17:27-35 © 2010 by the Society for Academic Emergency Medicine [ABSTRACT FROM AUTHOR]

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of mitochondrial fatty acid oxidation which is usually diagnosed in infancy or through neonatal screening. In the absence of population screening, adults with undiagnosed MCADD can be expected. This review discusses 14 cases that were identified during adulthood. The mortality of infantile patients is approximately 25% whereas in this adult case series it was shown it to be 50% in acutely presenting patients and 29% in total. Therefore, undiagnosed individuals are at risk of sudden fatal metabolic decompensation with high mortality. This review illustrates the need to consider the possibility of a fatty acid oxidation defect in an adult who presents with unexplained sudden clinical deterioration, particularly if precipitated by fasting or alcohol consumption. A history of unexplained sibling death may also raise the index of suspicion. There also needs to be appropriate clinical support for those patients identified clinically or as a result of family studies (sibling or parent). [ABSTRACT FROM AUTHOR]

A recent working group convened by the World Health Organization recommended that time to first or only episode of clinical malaria should be used to evaluate vaccine efficacy in phase III trials. However, calculating vaccine efficacy based on this endpoint misses important aspects of malaria disease and transmission. Here, we discuss the gaps that this approach leaves in predicting the potential public health impact of a vaccine and the challenges faced by vaccine trial designers. We examine the implications of current vaccine trial design on effectiveness studies and the next generation of malaria vaccines. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in developing a policy framework for tackling obesity crisis. The challenges are examined in terms of time frame as control of obesity is likely to take many years. The second challenge is difficulty about evidence as obesity is seen as a test case for policy changes in advance of perfect evidence. An ecological public health perspective is offered and the role of firm political leadership, supply chains and civil society are suggested to tackle the problem.

Nutrient loading from the Everglades Agricultural Area and nearby urban communities plus water flow rate and canal size have significantly influenced the amount of sediment and phosphorus (P) pools stored in the Water Conservation Area (WCA) canals in the Everglades. A study was conducted to characterize the potential impact that sediments might have on the overlying water column by conducting an inventory of total P (TP) and major P forms in sediments of all major canals in the WCAs. Sediment samples and sediment depth measurements were taken at transects every 1.6-km along all canals reaches. A total sediment volume of about 6.8 million m³, with a P mass of approximately 1808 Mg was estimated to be stored within all WCA canals, with the eastern canal accounting for 71% of the total sediment volume and about half of TP mass. Phosphorus fractions associated with Ca- and Mg-compounds and residual organic P (Po) were the dominant forms stored in these canals, with the greatest P mass observed in the western side of the WCAs. These results indicates that >80% of the TP mass stored in surface sediments in the WCAs is fairly stable, and represent an important long-term sink for P. Canal sediments from the eastern side of the WCAs were low in bulk density, highly organic and more susceptible to resuspension and transport during strong drainage events. These sediments showed higher Fe- and Al-bound P and organic-bound P fractions, making them more susceptible to changes in the redox potential of the sediments that could result in the long-term release of Fe-bound P to the overlying water column. [ABSTRACT FROM AUTHOR]

This study investigated the relationship between reported out-of-body experiences, certain psychological variables and personality characteristics. One hundred and sixtyseven participants completed a series of questionnaires to investigate differences amongst those participants reporting out-of-body experiences and those who were classified as believers or non-believers on: fantasy proneness, paranormal beliefs, psychological absorption, psychological association, somatoform dissociation, certain personality characteristics and OBE experience sensations. The findings revealed that experients were more fantasy prone, higher in their belief in the paranormal and displayed greater somatoform dissociation. Psychological absorption and dissociation were higher for believers than for either experients or non-believers and in relation to experients, fantasy proneness, paranormal beliefs and the personality dimensions of institution and feeling were significantly related, as were psychological absorption, psychological dissociation and somatoform dissociation. [ABSTRACT FROM AUTHOR]

Considers the political undertones of the British food policy. Reason behind the existence of political difficulties caused by food policy; Key characteristics of the government's policies.

Analyzes the food policy of the governing Labour Party in Great Britain. Provisions of the incumbent government's food policy; Factors that influenced the government's drafting of the policies.

Analyzes the food policy in Great Britain. Impact of the policies on public health; Government's prioritization of food safety concerns in drafting the policies; Weaknesses of the policies.

Background: Acute renal failure (ARF) can be triggered or aggravated by reactive oxygen species (ROS) but established ARF per se might also affect the antioxidant defence mechanisms of the organism. We evaluated a broad pattern of antioxidants in critically ill patients with multiple organ failure with (MOF-ARF) and without acute renal failure (MOF) to identify any potential involvement of renal dysfunction in the depletion of the antioxidant system.Methods: Observational study; 13 patients with MOF were investigated (9 with and 4 without ARF), and 17 healthy subjects served as controls. Blood samples were drawn after establishment of MOF. Plasma levels of ascorbate, alpha-tocopherol, retinol, beta-carotene, selenium and lipid peroxidation products (MDA) were determined and the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione-peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production (superoxide anion and hydrogen peroxide) in activated neutrophils was assessed.Results: Plasma levels of ascorbate, beta-carotene and selenium were reduced in both patient groups, when compared to controls. Decrease in selenium was more pronounced in the MOF-ARF group. MDA levels were increased in both groups, again being more pronounced in MOF-ARF patients compared to MOF patients. Hydrogen peroxide production by neutrophils from both patient groups was lower than from controls.Conclusion: A depression of the antioxidative system is present in critically ill patients with MOF. In patients with associated ARF this was even more pronounced and plasma MDA levels were higher, suggesting an additional effect on the antioxidative potential in the presence of renal dysfunction and/or renal replacement therapy. [ABSTRACT FROM AUTHOR]

The localization of MHC class II molecules (Ia) was studied by ultrastructural immunocytochemistry in murine bone marrow-derived macrophages stimulated by recombinant interferon-gamma (rIFN-γ). Ia molecules were detected on the plasma membrane and on the limiting membrane and internal structures of vesicular acidic compartments. Some of these vesicules also contained cathepsin B and/or cathepsin D. The use of BSA-gold, a marker of fluid phase endocytosis, allowed the identification of Ia-positive organelles as endocytic compartments. The first to be labelled with BSA gold also contained the cation-independent mannose 6-phosphate receptor (MPR) but not the 120,000 molecular weights lysosomal glycoprotein (Igp 120). Later on, BSA-gold appeared in Ia', MPR+, Igp 120+ compartments. Collectively these data suggest that intracellular Ia molecules are mainly present in early and late endosomes. [ABSTRACT FROM AUTHOR]

A serious and common accident in rural Kenyan homesteads is accidental ingestion of paraffin when it has been mistaken for water and offered to a young child. Here we report the incidence, parental practices and outcome of severe paraffin poisoning, requiring admission at Kilifi District Hospital, Kenya. Over a 2-year period, 48 children (0.5% of all admissions) were admitted with kerosene poisoning, constituting 62% of all poisoning cases. All cases were accidental. Ten per cent had induced vomiting. One child (2%) died. We suggest these data support assessment followed by implementation of practical and affordable measures to prevent paraffin poisoning. [ABSTRACT FROM AUTHOR]

Making a diagnosis of transient non-ketotic hyperglycinaemia (tNKH) can be difficult. We report an infant who presented in the neonatal period with symptoms of NKH. Metabolic studies performed on day 2 of life showed raised cerebrospinal fluid (CSF) and plasma glycine, and a CSF:plasma glycine ratio consistent with NKH; however, a liver biopsy performed on day 5 revealed normal liver glycine cleavage system activity. Subsequently, the child's clinical condition improved in the absence of any therapeutic medication. Clinical assessment and developmental follow-up at 5 months, 1 year, and 2 years were age-appropriate. Guidance for the investigation and management of future suspected cases of tNKH is discussed. [ABSTRACT FROM AUTHOR]

Oceanic mesoscale systems often produce heavy rainfall and can cause significant hazards in coastal regions and aviation. Surface features that are important in the evolution of these systems were examined combining the Advanced Scatterometer (ASCAT) on board the polar‐orbiting meteorological satellite series Metop‐A and ‐B and ground instrumentation; that is, Next Generation Weather Radars, soundings, buoys. Two case studies were analyzed, over the coastal United States, by reprojecting ASCAT wind and ground radar precipitation and wind retrievals over a common grid domain. ASCAT retrievals were in agreement with buoy and sounding measurements at distances greater than 30 km from the precipitation region. Enhanced uncertainty in ASCAT wind retrievals in heavy precipitation was represented by greater wind direction variability and increases in wind speed. Nevertheless, ASCAT was able to identify regions of convergence and divergence within the systems, as well as outflow boundaries associated with downdrafts, which agreed with wind fields retrieved from the single‐Doppler analysis. Quality flags reported by ASCAT were also examined against polarimetric radar retrievals. Thresholds for rain rate and median volume diameter (D0), corresponding to the boundary between flagged and unflagged ASCAT data, were variable among different cases. However, analysis of ice water path and liquid water path revealed that unflagged ASCAT data rarely exceeded approximately 0.5 kg/m2 in either parameter. Key Points: ASCAT is able to identify surface features that are of key importance for the evolution of the mesoscale systemsThe complementarity of ASCAT and radar wind retrievals provide additional information to assess the low‐level conditions within the precipitating systemOnly small amounts of vertically integrated ice and liquid water were found for unflagged ASCAT winds, as expected [ABSTRACT FROM AUTHOR]

Background: Toxin removal capacity (i.e., performance) of a dialyzer is not constant but diminishes during treatment, as the adsorption of proteins to the membrane provides an additional barrier to uremic solutes. We investigated time-resolving molecular weight retention changes among synthetic high-flux dialyzers and compared the results with recent data from a randomized controlled trial., Methods: In plasma recirculation experiments over 240 min, sieving coefficients (SC) for β2-microglobulin, myoglobin, and albumin were determined for the FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun). Molecular weight retention (MWR) curves were generated and the shifts over 120 min were characterized. Effective pore radius was determined, and the predicted albumin loss was compared with clinical data., Results: SC decreased over time for all dialyzers (mean relative decrease across all dialyzers: β2-microglobulin: 8.0% (120 min); myoglobin: 56.6% (240 min); albumin: 94.1% (240 min)). FX CorAL (7.3%, 52.6% and 91.1%) and ELISIO (7.7%, 51.0%, and 93.8%) showed a lower decrease than xevonta (9.0%, 66.2%, and 97.4%). For all dialyzers, MWR curves shifted toward lower molecular weight, with the lowest shift for FX CorAL (by 0.23 nm at SC50%, 120 min) and highest for xevonta (0.50 nm). FX CorAL had the highest slope over time and the smallest decrease in the effective pore radius (2 min: 2.31 nm, 120 min: 2.08 nm). Predicted albumin loss over 4 h was highest for xevonta (609.3 mg) and comparable between ELISIO (283.6 mg) and FX CorAL (313.3 mg)., Conclusions: Substantial differences in the temporal performance profile of dialyzers exist. The present approach allows the characterization of dialyzer permeability changes over time using standard, clinically relevant protein markers., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD., (© 2022 Wiley Periodicals LLC.)

Patients with haemato-oncological malignancies are one of the high-risk groups for a severe course in case of COVID-19 infections. Furthermore, vaccination results in significantly lower response rates in haematological malignancies and lower antibody levels in patients with solid cancer. We investigated efficacy and safety of a heterologous booster vaccination with Ad26.COV2.S DNA vector vaccine in haemato-oncological patients without antibody response after double-dose BNT162b2 messenger (m-)RNA COVID-19 vaccine. A total of 32 haemato-oncological non-responders to double-dose BNT162b2 received a heterologous booster vaccination with Ad26.COV2.S. Blood samples were assessed directly before the vaccination (T0) and four weeks after (T1). Safety assessment was performed using a standardised questionnaire. The overall response rate was 31%, with a mean (SD) antibody titre of 693·79 (1 096·99) binding activity units (BAU)/ml. Patients with chronic lymphocytic leukaemia or lymphoma showed a significantly lower response rate (P = 0·048). Adverse events were reported in 29·6% of patients, of which 7·1% were graded as severe, including grade III and IV events following the Common Terminology Criteria of Adverse Events (CTCAE). The heterologous booster vaccination with Ad26.COV2.S led to a serological response in nine out of 29 patients without response after double-dose BNT162b2. Furthermore, the vaccination was safe in our cohort, leading to mainly mild local and systemic reactions. Overall, this vaccination regimen should be further evaluated to increase the response rate in the highly vulnerable population of haemato-oncological patients., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Haemato-oncological patients are at risk in case of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Currently, vaccination is the best-evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato-oncological patients. A total of 259 haemato-oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS ® Anti-SARS-CoV-2-S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2-fold increased risk of non-responding (95% confidence interval 3·2-63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non-response. Low immunoglobulin G (IgG) level, lymphocyte- and natural killer (NK)-cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side-effects. Patients with side-effects developed a higher S/RBD-antibody titre compared to patients without side-effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non-response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non-response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato-oncological patients., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD., (© 2015 Wiley Periodicals, Inc.)