Should all acutely ill children in primary care be tested with point-of-care CRP: A cluster randomised trial

Background: Point-of-care blood C-reactive protein (CRP) testing has diagnostic value in helping clinicians rule out the possibility of serious infection. We investigated whether it should be offered to all acutely ill children in primary care or restricted to those identified as at risk on clinical assessment. Methods: Cluster randomised controlled trial involving acutely ill children presenting to 133 general practitioners (GPs) at 78 GP practices in Belgium. Practices were randomised to undertake point-of-care CRP testing in all children (1730 episodes) or restricted to children identified as at clinical risk (1417 episodes). Clinical risk was assessed by a validated clinical decision rule (presence of one of breathlessness, temperature ≥ 40 °C, diarrhoea and age 12-30 months, or clinician concern). The main trial outcome was hospital admission with serious infection within 5 days. No specific guidance was given to GPs on interpreting CRP levels but diagnostic performance is reported at 5, 20, 80 and 200 mg/L. Results: Restricting CRP testing to those identified as at clinical risk substantially reduced the number of children tested by 79.9 % (95 % CI, 77.8-82.0 %). There was no significant difference between arms in the number of children with serious infection who were referred to hospital immediately (0.16 % vs. 0.14 %, P = 0.88). Only one child with a CRP < 5 mg/L had an illness requiring admission (a child with viral gastroenteritis admitted for rehydration). However, of the 80 children referred to hospital to rule out serious infection, 24 (30.7 %, 95 % CI, 19.6-45.6 %) had a CRP < 5 mg/L. Conclusions: CRP testing should be restricted to children at higher risk after clinical assessment. A CRP < 5 mg/L rules out serious infection and could be used by GPs to avoid unnecessary hospital referrals

Is the black-widow pulsar PSR J1555-2908 in a hierarchical triple system?

The 559 Hz black-widow pulsar PSR J1555-2908, originally discovered in radio, is also a bright gamma-ray pulsar. Timing its pulsations using 12 yr of Fermi-LAT gamma-ray data reveals long-term variations in its spin frequency that are much larger than is observed from other millisecond pulsars. While this variability in the pulsar rotation rate could be intrinsic "timing noise", here we consider an alternative explanation: the variations arise from the presence of a very-low-mass third object in a wide multi-year orbit around the neutron star and its low-mass companion. With current data, this hierarchical-triple-system model describes the pulsar's rotation slightly more accurately than the best-fitting timing-noise model. Future observations will show if this alternative explanation is correct

Measurement of 1.7 to 74 MeV polarised gamma rays with the HARPO TPC

Current {\gamma}-ray telescopes based on photon conversions to electron-positron pairs, such as Fermi, use tungsten converters. They suffer of limited angular resolution at low energies, and their sensitivity drops below 1 GeV. The low multiple scattering in a gaseous detector gives access to higher angular resolution in the MeV-GeV range, and to the linear polarisation of the photons through the azimuthal angle of the electron-positron pair. HARPO is an R&D program to characterise the operation of a TPC (Time Projection Chamber) as a high angular-resolution and sensitivity telescope and polarimeter for {\gamma} rays from cosmic sources. It represents a first step towards a future space instrument. A 30 cm cubic TPC demonstrator was built, and filled with 2 bar argon-based gas. It was put in a polarised {\gamma}-ray beam at the NewSUBARU accelerator in Japan in November 2014. Data were taken at different photon energies from 1.7 MeV to 74 MeV, and with different polarisation configurations. The electronics setup is described, with an emphasis on the trigger system. The event reconstruction algorithm is quickly described, and preliminary measurements of the polarisation of 11 MeVphotons are shown.Comment: Proceedings VCI201

Revisiting an IgG Fc Loss-of-Function Experiment: The Role of Complement in HIV Broadly Neutralizing Antibody b12 Activity

The role of the complement system in HIV-1 immunity and pathogenesis is multifaceted, and an improved understanding of complement activities mediated by HIV-1-specific antibodies has the potential to inform and advance clinical development efforts. A seminal nonhuman primate challenge experiment suggested that complement was dispensable for the protective effect of the early broadly neutralizing antibody (bnAb) b12, but recent experiments have raised questions about the breadth of circumstances under which this conclusion may hold. Here, we reassess the original observation using Fc variants of IgG1 b12 that enhance complement activity and report that complement fixation on recombinant antigen, virions, and cells and complement-dependent viral and cellular lysis in vitro vary among bnAbs. Specifically, while the clinically significant V3 glycan-specific bnAb 10-1074 demonstrates activity, we found that b12 does not meaningfully activate the classical complement cascade. Consistent with avid engagement by C1q and its complex system of regulatory factors, these results suggest that complement-mediated antibody activities demonstrate a high degree of context dependence and motivate revisiting the role of complement in antibody-mediated prevention of HIV-1 infection by next-generation bnAbs in new translational studies in animal models. IMPORTANCE Given the suboptimal outcome of VRC01 antibody-mediated prevention of HIV-1 infection in its first field trial, means to improve diverse antiviral activities in vivo have renewed importance. This work revisits a loss-of-function experiment that investigated the mechanism of action of b12, a similar antibody, and finds that the reason why complement-mediated antiviral activities were not observed to contribute to protection may be the inherent lack of activity of wild-type b12, raising the prospect that this mechanism may contribute in the context of other HIV-specific antibodies

Report of the GDR working group on the R-parity violation

This report summarizes the work of the "R-parity violation group" of the French Research Network (GDR) in Supersymmetry, concerning the physics of supersymmetric models without conservation of R-parity at HERA, LEP, Tevatron and LHC and limits on R-parity violating couplings from various processes. The report includes a discussion of the recent searches at the HERA experiment, prospects for new experiments, a review of the existing limits, and also theoretically motivated alternatives to R-parity and a brief discussion on the implications of R-parity violation on the neutrino masses.Comment: 60 pages, LaTeX, 22 figures, 2 table

The predictive value of the NICE "red traffic lights" in acutely ill children

Objective: Early recognition and treatment of febrile children with serious infections (SI) improves prognosis, however, early detection can be difficult. We aimed to validate the predictive rule-in value of the National Institute for Health and Clinical Excellence (NICE) most severe alarming signs or symptoms to identify SI in children. Design, Setting and Participants: The 16 most severe ("red") features of the NICE traffic light system were validated in seven different primary care and emergency department settings, including 6,260 children presenting with acute illness. Main Outcome Measures: We focussed on the individual predictive value of single red features for SI and their combinations. Results were presented as positive likelihood ratios, sensitivities and specificities. We categorised "general" and "disease-specific" red features. Changes in pre-test probability versus post-test probability for SI were visualised in Fagan nomograms. Results: Almost all red features had rule-in value for SI, but only four individual red features substantially raised the probability of SI in more than one dataset: "does not wake/stay awake", "reduced skin turgor", "non-blanching rash", and "focal neurological signs". The presence of ≥3 red features improved prediction of SI but still lacked strong rule-in value as likelihood ratios were below 5. Conclusions: The rule-in value of the most severe alarming signs or symptoms of the NICE traffic light system for identifying children with SI was limited, even when multiple red features were present. Our study highlights the importance of assessing the predictive value of alarming signs in clinical guidelines prior to widespread implementation in routine practice