Explore the vast range of titles available.

Paul Scherrer and Peter Debye developed powder X-ray diffraction together, but it was Scherrer who figured out how to determine the size of crystallites from the broadening of diffraction peaks.

Diagnosing sleep-disordered breathing in children with suspected sleep-disordered breathing Sleep questionnaires, combined sleep questionnaires and ‘protocol-driven’ clinical assessments, sleep video recordings and sleep audio recordings Children without comorbidities Recommendations The Sleep-Related Breathing Disorder scale of the Paediatric Sleep Questionnaire (SRBD-PSQ), with a cut-off of ≥0.33, or Obstructive Sleep Apnoea-18 item questionnaire (OSA-18), with a cut-off of ≥0.60, can be considered for diagnosing moderate-to-severe SDB in children of at least 2 years of age with no comorbidities. While pulse oximetry is non-discriminatory at all ages, particular caution is required in using oximetry to diagnose OSA in children under 2 years of age as children in this age group are predisposed to central sleep apnoea (CSA) (as a result of developmental immaturity) and oxygen desaturations cannot discriminate between obstructive and central events. If hypoventilation is suspected, please refer to the ‘Pulse oximetry and carbon dioxide (CO2) monitoring’ recommendations and GPPs below. The American Academy of Sleep Medicine (AASM) recommends scoring hypoventilation during sleep when >25% of the total sleep time, as measured by either the arterial PCO2 or surrogate (transcutaneous or end tidal which is more relevant in paediatrics), is spent with a PCO2 >50 mm Hg/6.7 kPa.3 Home monitoring (pulse oximetry or CRSS) Recommendation Home CRSS can be considered for diagnosing SDB in children without comorbidities where the patients and/or carers are deemed appropriate for implementing a home sleep study.

miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1). We enrolled men and postmenopausal or hysterectomised women (aged 18–65 years) with chronic HCV genotype 1, 3, or 4 infection diagnosed at least 24 weeks before screening who were either treatment naive to or relapsed after interferon-α based therapy. Patients with co-infection (hepatitis B virus or HIV infection), evidence of decompensated liver disease, or a history of hepatocellular carcinoma were excluded. Randomisation was done by an independent, unblinded, statistician using the SAS procedure Proc Plan. The first cohort received one subcutaneous injection of 2 mg/kg RG-101 or placebo; the second cohort received one subcutaneous injection of 4 mg/kg or placebo. Patients were followed up for 8 weeks (all patients) and up to 76 weeks (patients with no viral rebound and excluding those who were randomised to the placebo group) after randomisation. The primary objective was safety and tolerability of RG-101. This trial was registered with EudraCT, number 2013-002978-49. Between June 4, 2014, and Oct 27, 2014, we enrolled 32 patients with chronic HCV genotype 1 (n=16), 3 (n=10), or 4 (n=6) infections. In the first cohort, 14 patients were randomly assigned to receive 2 mg/kg RG-101 and two patients were randomly assigned to receive placebo, and in the second cohort, 14 patients were randomly assigned to receive 4 mg/kg RG-101 and two patients were randomly assigned to receive placebo. Overall, 26 of the 28 patients dosed with RG-101 reported at least one treatment-related adverse event. At week 4, the median viral load reduction from baseline was 4·42 (IQR 3·23–5·00) and 5·07 (4·19–5·35) log10 IU/mL in patients dosed with 2 mg/kg RG-101 or 4 mg/kg RG-101. Three patients had undetectable HCV RNA levels 76 weeks after a single dose of RG-101. Viral rebound at or before week 12 was associated with the appearance of resistance associated substitutions in miR-122 binding regions in the 5′ UTR of the HCV genome. This study showed that one administration of 2 mg/kg or 4 mg/kg RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated anti-miR-122 oligonucleotide, was well tolerated and resulted in substantial viral load reduction in all treated patients within 4 weeks, and sustained virological response in three patients for 76 weeks. Regulus Therapeutics, Inc.

The search strategy is available for review in Online supplement appendix 12 of the full guideline.1 Critical appraisal and GRADE analysis of the evidence After an initial screening to determine relevance to the clinical questions, each paper was assessed to determine if it addressed: Following data extraction from the ‘accepted’ papers, evidence profiles were generated for each of the clinical questions and the quality of the evidence was assessed using the GRADE principles.5 Where GRADE analysis was not possible, but the evidence was deemed important enough to be included in the guideline, the evidence has been listed as (Ungraded), denoting that inclusion was reached by consensus of the Guideline Development Group (GDG). A definition of the GRADE scores is shown in table 1.Table 1 GRADE score definitions GRADE Definition High High confidence that the true effect is close to the estimated effect Moderate Moderate confidence that the true effect is close to the estimated effect Low Low confidence that the true effect is close to the estimated effect Very low Very low confidence that the true effect is close to the estimated effect Ungraded GRADE analysis not possible, but evidence deemed important GRADE, Grading of Recommendations, Assessment, Development and Evaluation. GRADE specifies two categories of strength for a recommendation as shown in table 2.Table 2 Explanation of the terminology used in BTS recommendations Strength Benefits and risks Implications Strong Recommended, so ‘offer’ Benefits appear to outweigh the risks (or vice versa) for the majority of the target group Most service users would want to, or should receive this intervention Conditional Suggested, so ‘consider’ Risks and benefits are more closely balanced, or there is more uncertainty in likely service users’ values and preferences Service users should be supported to arrive at a decision based on their values and preferences BTS, British Thoracic Society.

Suet Leung, Jiangchun Xu and colleagues report exome sequencing of 22 gastric cancers. They found that genes involved in chromatin modification were commonly mutated, including ARID1A encoding an SWI/SNF chromatin-remodeling complex component that had a high rate of mutation. Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis 1 , 2 . Beyond mutations in TP53 , alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A , which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53 . Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer.

Bedside point-of-care ultrasound (POCUS) is increasingly used to assess medical patients. At present, no consensus exists for what POCUS curriculum is appropriate for internal medicine residency training programs. This document details the consensus-based recommendations by the Canadian Internal Medicine Ultrasound (CIMUS) group, comprising 39 members, representing 14 institutions across Canada. Guiding principles for selecting curricular content were determined a priori. Consensus was defined as agreement by at least 80% of the members on POCUS applications deemed appropriate for teaching and assessment of trainees in the core (internal medicine postgraduate years [PGY] 1–3) and expanded (general internal medicine PGY 4–5) training programs. We recommend four POCUS applications for the core PGY 1–3 curriculum (inferior vena cava, lung B lines, pleural effusion, and abdominal free fluid) and three ultrasound-guided procedures (central venous catheterization, thoracentesis, and paracentesis). For the expanded PGY 4–5 curriculum, we recommend an additional seven applications (internal jugular vein, lung consolidation, pneumothorax, knee effusion, gross left ventricular systolic function, pericardial effusion, and right ventricular strain) and four ultrasound-guided procedures (knee arthrocentesis, arterial line insertion, arterial blood gas sampling, and peripheral venous catheterization). These recommendations will provide a framework for training programs at a national level.

Species turnover and its components related to replacement and nestedness form a significant element of diversity that is historically poorly accounted for in conservation planning. To inform biodiversity conservation and contribute to a broader understanding of patterns in species turnover, we undertook a floristic survey of 160 plots along an 870 km transect across oligotrophic sandplains, extending from the mesic south coast to the arid interior of south-western Australia. A nested survey design was employed to sample distances along the transect as evenly as possible. Species turnover was correlated with geographic distance at both regional and local scales, consistent with dispersal limitation being a significant driver of species turnover. When controlled for species richness, species replacement was found to be the dominant component of species turnover and was uniformly high across the transect, uncorrelated with either climatic or edaphic factors. This high replacement rate, well documented in the mega-diverse south-west, appears to also be a consistent feature of arid zone vegetation systems despite a decrease in overall species richness. Species turnover increased rapidly with increasing extent along the transect reaching an asymptote at ca. 50 km. These findings are consistent with earlier work in sandplain and mallee vegetation in the south-west and suggests reserve based conservation strategies are unlikely to be practicable in the south-western Australia sandplains when communities are defined by species incidence rather than dominance.