The Minority Spin Surface Bands of CoS2(001)

Angle-resolved photoemission was used to study the surface electronic band structure of high quality single crystals of ferromagnetic CoS2 (below 120 K). Strongly dispersing Co t2g bands are identified along the 100 k direction, the ¯–¯X line of the surface Brillouin zone, in agreement with model calculations. The calculated surface band structure includes corrections for the previously determined surface structure of CoS2(001) and is in general agreement with the experimental photoemission spectra in the region of the Fermi level. There is evidence of the existence of several minority spin surface states, falling into a gap of the projected minority spin bulk CoS2(001) band structure

The Surface Stability of CoS2(100)

The stability of various possible terminations of the CoS2 (1 × 1) surface have been explored and theoretical expectations are found to agree with experiment. With extensive annealing, there is a phase separation at the (100) surface of CoS2. Sulfur segregation to the surface leads to a significant change in the largely sulfur bands due to changes in the hybridized bands, with cobalt. Resonant photoemission spectra indicate clearly that the hybridized cobalt and sulfur bands, characteristic of the CoS2 bulk, lie at higher binding energies than those of segregated sulfur layers. This is discussed in terms of the stability of various surface structures

Clinical trials in amyotrophic lateral sclerosis:a systematic review and perspective

Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease modifying drugs remain scarce. To understand the challenges of trial design and delivery, we performed a systematic review of phase II, phase II/III and phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15000 people with amyotrophic lateral sclerosis. 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis

Prevalence and Determinants of Metabolic Syndrome among Women in Chinese Rural Areas

BACKGROUND AND AIMS: Metabolic syndrome (MS) is prevalent in recent years but few data is reported in the rural areas in China. The aim of this study was to examine MS prevalence and its risk factors among women in rural China. METHODS AND RESULTS: The Nantong Metabolic Syndrome Study (NMSS), a population based cross-sectional study, was conducted during 2007-2008 in Nantong, China. In person interviews, blood glucose and lipid measurements were completed for 13,505 female participants aged 18-74 years. The International Diabetes Federation (IDF), the US Third Report of the National Cholesterol Education Program, the Adult Treatment Panel (ATPIII) and modified ATPIII for Asian population has determined three criteria of MS. These criteria for MS were used and compared in this study. The prevalence of MS was 22.0%, 16.9% and 23.3% according to IDF, ATPIII and ATPIII-modified criteria, respectively. Levels of agreement of these criteria for MS were above 0.75. We found that vigorous-intensity of occupational physical activity was associated with a low prevalence of MS with OR of 0.76 (95% confidence interval (CI): 0.63-0.91). Rice wine drinkers (alcohol >12.8 g/day) had about 34% low risks of developing MS with OR of 0.66 (95% CI: 0.48-0.91), compared with non-drinkers. Odds ratio of MS was 1.81 (95% CI: 1.15-2.84) in women who smoked more than 20 pack-years, compared to non-smokers. Odds ratio of MS was 1.56 (95% CI: 1.25-1.95) in women who had familial history of diseases, including hypertension, diabetes and stroke, compared to women without familial history of those diseases. CONCLUSION: MS is highly prevalent among women in rural China. Both physical activity and rice wine consumption play a protective role, while family history and smoking are risk factors in MS development. Educational programs should be established for promoting healthy lifestyles and appropriate interventions in rural China

Base-Pair Resolution DNA Methylation Sequencing Reveals Profoundly Divergent Epigenetic Landscapes in Acute Myeloid Leukemia

We have developed an enhanced form of reduced representation bisulfite sequencing with extended genomic coverage, which resulted in greater capture of DNA methylation information of regions lying outside of traditional CpG islands. Applying this method to primary human bone marrow specimens from patients with Acute Myelogeneous Leukemia (AML), we demonstrated that genetically distinct AML subtypes display diametrically opposed DNA methylation patterns. As compared to normal controls, we observed widespread hypermethylation in IDH mutant AMLs, preferentially targeting promoter regions and CpG islands neighboring the transcription start sites of genes. In contrast, AMLs harboring translocations affecting the MLL gene displayed extensive loss of methylation of an almost mutually exclusive set of CpGs, which instead affected introns and distal intergenic CpG islands and shores. When analyzed in conjunction with gene expression profiles, it became apparent that these specific patterns of DNA methylation result in differing roles in gene expression regulation. However, despite this subtype-specific DNA methylation patterning, a much smaller set of CpG sites are consistently affected in both AML subtypes. Most CpG sites in this common core of aberrantly methylated CpGs were hypermethylated in both AML subtypes. Therefore, aberrant DNA methylation patterns in AML do not occur in a stereotypical manner but rather are highly specific and associated with specific driving genetic lesions

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies