The test characteristics of head circumference measurements for pathology associated with head enlargement: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The test characteristics of head circumference (HC) measurement percentile criteria for the identification of previously undetected pathology associated with head enlargement in primary care are unknown.</p> <p>Methods</p> <p>Electronic patient records were reviewed to identify children age 3 days to 3 years with new diagnoses of intracranial expansive conditions (IEC) and metabolic and genetic conditions associated with macrocephaly (MGCM). We tested the following HC percentile threshold criteria: ever above the 95^th, 97^th, or 99.6^thpercentile and ever crossing 2, 4, or 6 increasing major percentile lines. The Centers for Disease Control and World Health Organization growth curves were used, as well as the primary care network (PCN) curves previously derived from this cohort.</p> <p>Results</p> <p>Among 74,428 subjects, 85 (0.11%) had a new diagnosis of IEC (n = 56) or MGCM (n = 29), and between these 2 groups, 24 received intervention. The 99.6^thpercentile of the PCN curve was the only threshold with a PPV over 1% (PPV 1.8%); the sensitivity of this threshold was only 15%. Test characteristics for the 95th percentiles were: sensitivity (CDC: 46%; WHO: 55%; PCN: 40%), positive predictive value (PPV: CDC: 0.3%; WHO: 0.3%; PCN: 0.4%), and likelihood ratios positive (LR+: CDC: 2.8; WHO: 2.2; PCN: 3.9). Test characteristics for the 97th percentiles were: sensitivity (CDC: 40%; WHO: 48%; PCN: 34%), PPV (CDC: 0.4%; WHO: 0.3%; PCN: 0.6%), and LR+ (CDC: 3.6; WHO: 2.7; PCN: 5.6). Test characteristics for crossing 2 increasing major percentile lines were: sensitivity (CDC: 60%; WHO: 40%; PCN: 31%), PPV (CDC: 0.2%; WHO: 0.1%; PCN: 0.2%), and LR+ (CDC: 1.3; WHO: 1.1; PCN: 1.5).</p> <p>Conclusions</p> <p>Commonly used HC percentile thresholds had low sensitivity and low positive predictive value for diagnosing new pathology associated with head enlargement in children in a primary care network.</p

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Constitutional Conflict in Hong Kong Under Chinese Sovereignty

© 2016, T.M.C. Asser Press.The protracted constitutional conflicts between the Chinese state and Hong Kong society over the pace and form of democratization have become a source of political instability. This article sheds new light on these dynamics by analyzing the two sides as locked in a coordination dilemma: both have important common interests to coordinate with each other, but both rank in divergent ways their preferences for and against introducing competitive electoral arrangements into Hong Kong. It is shown how the unwillingness of either side to compromise has caused the gradual breakdown of coordination as focal points like the Basic Law have eroded, culminating in the Umbrella Revolution of 2014, the largest and longest-lasting popular movement in Hong Kong history. The bloodless ending of the Movement is chronicled, along with the persistence of political stalemate in this highly anomalous polity, known throughout the world for its combination of genuine civil liberties with authoritarian rule.Link_to_subscribed_fulltex

Re-evaluation of medical findings in alleged shaken baby syndrome and abusive head trauma in Norwegian courts fails to support abuse diagnoses

Aim The criteria for diagnosing abusive head trauma (AHT) are not well defined and this condition might be diagnosed on failing premises. Our aim was to review criminal AHT cases in Norwegian courts by scrutinising the underlying medical documentation. Methods Cases were identified in the data registry for Norwegian courts from 2004 to 2015. Documentation was obtained from relevant health institutions. The medical co-authors first made independent evaluations of the documentation for each child, followed by a consensus evaluation. Results A total of 17 children (11 boys) were identified, all diagnosed as AHT by court appointed experts, 15 were infants (mean age 2.6 months). A high proportion (41.2%) was born to immigrant parents and 31.3% were premature. The medical findings could be explained by alternative diagnoses in 16 of the 17 children; 8 boys (7 infants – mean age 2.9 months) had clinical and radiological characteristics compatible with external hydrocephalus complicated by chronic subdural haematoma. Six children (five infants with mean age 2.1 months) had a female preponderance and findings compatible with hypoxic ischaemic insults. Conclusion The medical condition in most children had not necessarily been caused by shaking or direct impact, as was originally concluded by the court experts