Alternating-Spin Ladders in a Magnetic Field: New Magnetization Plateaux

We study numerically the formation of magnetization plateaux with the Lanczos method in 2-leg ladders with mixed spins of magnitudes $(S_1,S_2)=(1,1/2)$ located at alternating positions along the ladder and with dimerization $\gamma$. For interchain coupling $J'>0$ and $\gamma=0$, we find normalized plateaux at $m=1/3$ starting at zero field and $m=1$ (saturation), while when $\gamma \ne 0$ is columnar, another extra plateau at $m=2/3$ shows up. For $J'<0$, when $\gamma<\gamma_c(J')$ we find no plateau while for $\gamma>\gamma_c(J')$ we find four plateaux at $m=0,1/3,2/3,1$. We also apply several approximate analytical methods (Spin Wave Theory, Low-Energy Effective Hamiltonians and Bosonization) to understand these findings and to conjeture the behaviour of ferrimagnetic ladders with a bigger number of legs.Comment: REVTEX file, 7 pages, 6 eps Figure

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Temporal association of rotavirus vaccination and genotype circulation in South Africa : observations from 2002 to 2014

BACKGROUND : Rotavirus vaccination has reduced diarrhoeal morbidity and mortality globally. The monovalent rotavirus vaccine was introduced into the public immunization program in South Africa (SA) in 2009 and led to approximately 50% reduction in rotavirus hospitalization in young children. The aim of this study was to investigate the rotavirus genotype distribution in SA before and after vaccine introduction. MATERIALS AND METHODS : In addition to pre-vaccine era surveillance conducted from 2002-2008 at Dr George Mukhari Hospital (DGM), rotavirus surveillance among children <5 years hospitalized for acute diarrhoea was established at seven sentinel sites in SA from April 2009 to December 2014. Stool specimens were screened by enzyme immunoassay and rotavirus positive specimens genotyped using standardised methods. RESULTS : At DGM, there was a significant decrease in G1 strains from pre-vaccine introduction (34%; 479/1418; 2002-2009) compared to post-vaccine introduction (22%; 37/170; 2010-2014; p for trend <0.001). Similarly, there was a significant increase in non-G1P[8] strains at this site (p for trend < 0.001). In expanded sentinel surveillance, when adjusted for age and site, the odds of rotavirus detection in hospitalized children with diarrhoea declined significantly from 2009 (46%; 423/917) to 2014 (22%; 205/939; p<0.001). The odds of G1 detection declined significantly from 2009 (53%; 224/421) to 2010-2011 (26%; 183/703; aOR=0.5; p<0.001) and 2012-2014 (9%; 80/905; aOR=0.1; p<0.001). Non-G1P[8] strains showed a significant increase from 2009 (33%; 139/421) to 2012-2014 (52%; 473/905; aOR=2.5; p<0.001). CONCLUSIONS : Rotavirus vaccination of children was associated with temporal changes in circulating genotypes. Despite these temporal changes in circulating genotypes, the overall reduction in rotavirus disease in South Africa remains significant.The expanded diarrhoea sentinel surveillance programme was funded by GlaxoSmithKline (E-Track 200238). NAP received personal fees from GlaxoSmithKline, Merck and Aspen Pharma. MJG received personal fees from GlaxoSmithKline and funding from PATH Vaccine Solutions. CC received personal fees from Sanofi Pasteur and Pfizer. SAM received personal fees from Pfizer and funding from PATH, Novartis and GlaxoSmithKline.http://www.elsevier.com/locate/vaccine2019-11-12hj2017Medical Virolog

Improved correlation between animal and human potency of non-steroidal anti-inflammatory drugs using quantitative structure–activity relationships (QSARs)

Animal models are known not to predict human responses well, in general. However, we have been able to demonstrate that, for a series of non-steroidal anti-inflammatory drugs that are or were in clinical use, the incorporation of two simple physicochemical properties results in excellent correlations between human and rodent potencies for anti-inflammatory, analgesic and anti-pyretic activities. This has the potential to allow the use of historical data to improve drug development

Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: The EASIE post-hoc analysis and extension trial

AbstractAimWe examined the effects of adding glargine to metformin–sitagliptin (MS+G) or sitagliptin to metformin–glargine (MG+S) therapy in type 2 diabetic persons uncontrolled after 24-week MS or MG dual therapy.MethodsSubjects with A1c≥7% on MS or MG treatment were respectively given glargine (0.2U/kg starting dose) or sitagliptin (100mg daily) for 12weeks. The primary endpoint was number of subjects attaining A1c goal defined as <7%.ResultsAfter receiving 24-week MS or MG dual therapy in the original EASIE Study, 42% (104/248) on MS and 68% (152/224) on MG attained A1c<7% (p<0.0001). The reduction in A1c was negatively associated with baseline fasting blood glucose (FBG) only in the MG group. Reduction in A1c was not related to baseline postprandial blood glucose (PPBG) in either the MG or MS group. Amongst 194 eligible patients, 57.7% (n=111) entered the 12-week extension trial [MS+G:74/131, 57.3%; MG+S:37/63, 58.7%) with 55 (51.9%) subjects attaining goal [MS+G:59.2%; MG+S:37.1%] at week 12. The final insulin dosage was similar in both groups [MS+G: 0.46U/kg; MG+S: 0.45U/kg] with a higher rate of hypoglycemia in the MG+S (6.5 events/patient-year) than the MS+G group (3.2 events/patient-year), although neither group had severe hypoglycemia.ConclusionIn metformin-treated type 2 diabetes patients, high fasting BG predicted greater A1c reductions with the addition of glargine, but not with sitagliptin. In subjects uncontrolled with 6-month dual therapy of MS or MG, 50% attained A1c<7% with triple therapy of MS+G or MG+S in 12weeks. The increased rate of hypoglycemia with MG+S (but not with MS+G) underlines the need to take measures to avoid the hypoglycemia