Results of a multicentre UK-wide compassionate use programme evaluating the efficacy of idelalisib monotherapy in relapsed, refractory follicular lymphoma.

Follicular lymphoma (FL) is an indolent B-cell malignancy with a variable course. Standard immuno-chemotherapy incorporate alkylator and anti-CD20 monoclonal antibody as first line (Rummel et al, 2013) commonly followed by 24 months rituximab maintenance (Salles et al, 2008). Anthracycline, purine analogue, and alkylator combination are used at relapse and younger patients may have remissions consolidated with autologous or allogeneic stem-cell transplantation (alloSCT) (Kothari et al, 2014). Relapsed or refractory (R/R) FL in patients unfit for transplantation or post-transplantation is incurable, and remains an unmet need

Low estimated glomerular filtration rate and pneumonia in stroke patients: findings from a prospective stroke registry in the East of England

Priya Vart,1,2 Joao H Bettencourt-Silva,3,4 Anthony K Metcalf,3,4 Kristian M Bowles,3,4 John F Potter,3,4 Phyo K Myint1,3,4 1Ageing Clinical and Experimental Research, Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UK; 2Radboud Institute for Health Sciences, Department for Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands; 3Stroke Research Group, Norfolk and Norwich University Hospital, Norwich, UK; 4Norwich Medical School, University of East Anglia, Norwich, UK Purpose: Low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73 m2) is a recognized risk factor for pneumonia in general population. While pneumonia is common after stroke, the association between levels of eGFR and pneumonia in stroke patient population has not yet been examined thoroughly. Patients and methods: Using data of 10,329 patients from the Norfolk and Norwich Stroke Registry between January 2003 and April 2015, we examined the association of poststroke pneumonia (in-hospital and after discharge) with low eGFR and when eGFR is divided into the complete spectrum of clinically relevant categories; (≥90) (ref.), 60–89, 45–59, 30–44, 15–30, and <15 mL/min/1.73 m2). Results: In all, 1,519 (14.7%) developed in-hospital pneumonia and 1,037 (12.9%) developed pneumonia after hospital discharge. In age- and sex-adjusted model, low eGFR was associated with in-hospital pneumonia (subdistribution hazard ratio (sHR): 1.13; 95% CI: 1.01–1.25) and pneumonia after discharge (sHR: 1.20; 95% CI: 1.07–1.38). In fully adjusted model, association remained significant for pneumonia after hospital discharge. When eGFR was categorized in all clinically relevant categories, association with in-hospital pneumonia tended to be “U” shaped (eg, compared to eGFR ≥90, sHR for 60–89 was 0.78; 95% CI: 0.62–0.99 and for <15 was 1.06; 95% CI: 0.71–1.60) and association with pneumonia after discharge tended to increase with decline in eGFR level such that risk was almost two fold higher at eGFR <15 (sHR: 1.85; 95% CI: 1.01–3.51). Association for in-hospital pneumonia was driven mainly by aspiration pneumonia, whereas association in stroke survivors was predominantly for nonaspiration pneumonia. Conclusion: In stroke patients, low eGFR at admission was associated with pneumonia, particularly severely reduced eGFR with nonaspiration pneumonia after hospital discharge. eGFR could form the basis for identifying patients at high risk of poststroke pneumonia. Keywords: stroke, eGFR, prognosis, epidemiolog

ES-Cell Derived Hematopoietic Cells Induce Transplantation Tolerance

Background: Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES) cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs). Up till now, however, it has been difficult to generate stable hematopoietic cells from ES cells. Methodology/Principal Findings: Here, we derived CD45 + HPCs from HOXB4-transduced ES cells and showed that they poorly express MHC antigens. This property allowed their long-term engraftment in sublethally irradiated recipients across MHC barriers without the need for immunosuppressive agents. Although donor cells declined in peripheral blood over 2 months, low level chimerism was maintained in the bone marrow of these mice over 100 days. More importantly, chimeric animals were protected from rejection of donor-type cardiac allografts. Conclusions: Our data show, for the first time, the efficacy of ES-derived CD45 + HPCs to engraft in allogenic recipient

Photographed Rapid HIV Test Results Pilot Novel Quality Assessment and Training Schemes

HIV rapid diagnostic tests (RDTs) are now used widely in non-laboratory settings by non-laboratory-trained operators. Quality assurance programmes are essential in ensuring the quality of HIV RDT outcomes. However, there is no cost-effective means of supplying the many operators of RDTs with suitable quality assurance schemes. Therefore, it was examined whether photograph-based RDT results could be used and correctly interpreted in the non-laboratory setting. Further it was investigated if a single training session improved the interpretation skills of RDT operators. The photographs were interpreted, a 10-minute tutorial given and then a second interpretation session was held. It was established that the results could be read with accuracy. The participants (n = 75) with a range of skills interpreted results (>80% concordance with reference results) from a panel of 10 samples (three negative and seven positive) using four RDTs. Differences in accuracy of interpretation before and after the tutorial were marked in some cases. Training was more effective for improving the accurate interpretation of more complex results, e.g. results with faint test lines or for multiple test lines, and especially for improving interpretation skills of inexperienced participants. It was demonstrated that interpretation of RDTs was improved using photographed results allied to a 10-minute training session. It is anticipated that this method could be used for training but also for quality assessment of RDT operators without access to conventional quality assurance or training schemes requiring wet samples

The Association between Pro-Social Attitude and Reproductive Success Differs between Men and Women

The evolution of pro-social attitude and cooperation in humans is under debate. Most of the knowledge on human cooperation results from laboratory experiments and theoretic modeling. Evolutionary explanations, however, rest upon fitness consequences. We therefore examined fitness correlates of pro-social behavior in a real life setting, analyzing data from the Wisconsin Longitudinal Study (n = 2545 men, 2967 women). We investigated whether pro-social attitude, proxied by self reported voluntary work, is associated with lifetime reproductive success. We find a sex difference in the association between pro-social attitude and offspring number. In men, a pro-social attitude was associated with higher offspring number, whereas in women, it was associated with lower offspring count. To our knowledge, this is the first study to demonstrate fitness consequences of pro-social behavior towards strangers. We conclude that analysing real life settings may help to explain the evolutionary forces leading to pro-social behavior in humans and speculate that these factors might differ between the sexes

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Evaluation of Type-Specific Real-Time PCR Assays Using the LightCycler and J.B.A.I.D.S. for Detection of Adenoviruses in Species HAdV-C

Sporadically, HAdVs from species HAdV-C are detected in acute respiratory disease outbreaks. To rapidly type these viruses, we designed real-time PCR assays that detect and discriminate between adenovirus types HAdV-C1, -C2, -C5, and -C6. Sixteen clinical isolates from the California Department of Public Health were used to validate the new assays. Type-specific TaqMan real-time PCR assays were designed and used independently to successfully identify 16 representative specimens. The lower limit of detection for our LightCycler singleplex real-time PCR assays were calculated to be 100, 100, 100, and 50 genomic copies per reaction for HAdV-C1, HAdV-C2, HAdV-C5 and HAdV-C6, respectively. The results for the singleplex J.B.A.I.D.S. assays were similar. Our assays did not cross-react with other adenoviruses outside of species HAdV-C, respiratory syncytial virus, influenza, or respiratory disease causing bacteria. These assays have the potential to be useful as diagnostic tools for species HAdV-C infection

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding