Mathematical structures for decoding projective geometry codes

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Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Environmentalism, pre-environmentalism, and public policy

In the last decade, thousands of new grassroots groups have formed to oppose environmental pollution on the basis that it endangers their health. These groups have revitalized the environmental movement and enlarged its membership well beyond the middle class. Scientists, however, have been unable to corroborate these groups' claims that exposure to pollutants has caused their diseases. For policy analysts this situation appears to pose a choice between democracy and science. It needn't. Instead of evaluating the grassroots groups from the perspective of science, it is possible to evaluate science from the perspective of environmentalism. This paper argues that environmental epidemiology reflects ‘pre-environmentalist’ assumptions about nature and that new ideas about nature advanced by the environmental movement could change the way scientists collect and interpret data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45449/1/11077_2005_Article_BF01006494.pd

Long-term, Harvest-based Monitoring of Ringed Seal Body Condition and Reproduction in Canada’s Western Arctic: An Update through 2019 + Supplementary Appendix 1 (See Article Tools)

The circumpolar Arctic ringed seal (Pusa hispida) occupies its fast-ice breeding habitat for four to five months during winter and the pack ice or open water of adjacent areas for the rest of the year. From 1971 – 78 and 1992 – 2019, we sampled approximately 100 ringed seals annually from western Prince Albert Sound (WPAS), the prime ringed seal fast-ice breeding habitat in Canada’s Western Arctic, adjacent to primary overwinter foraging habitat in eastern Amundsen Gulf (EAG). As our metric of body condition, we measured ventral blubber depth corrected for body size. As our metrics of reproduction, we measured the annual ovulation rate of multiparous females and percent pups in the open-water harvest. We examined these biological parameters in relation to the winter Arctic Oscillation Index (winAOI) and the timing of sea ice clearance in EAG in spring. There were no significant effects of age or sample month (June or July) on adult blubber depth, but significant sex and year effects and, in females, ovulation status effects. Across the series, as we have observed previously through 2011, there was a sustained temporal declining trend in blubber depth in adults of both sexes. There was no temporal trend in residual blubber depth, no correlation between blubber depth and sea ice clearance date in EAG, and a quasi-cyclic pattern in blubber depth that tracked some of the phases of the winAOI. Annual ovulation rates were mainly in the 80% – 100% range and correlated with percent pups in the open harvest in the same year. Three (1974, 2005, 2012) of the 36 y experienced reproductive failures, when over 50% of the multiparous females failed to ovulate. In each case, ovulation rates returned to normal within 1 – 3 y. Low annual ovulation rates were correlated with late sea ice clearance in EAG in spring, with two widespread ovulation failure events taking place in years when spring sea ice clearance was delayed by five to six weeks. The most recent ovulation failure (2012) differed in that it came in an average ice year but at the end of a six-year sequence of negative residual mean blubber depths. Earlier spring sea ice clearance in WPAS, based on the observed rate of 3.8 d per decade, would on average not result in the physical loss of sea ice for pupping in this core habitat before 2140. The mechanisms involved in the sustained declining temporal trend in body condition, linkage with some phases of the winAOI, and the temporary but episodic failures of ovulation are complex and not fully explained by either the timing of sea ice clearance or the winAOI. Until the complex mix of factors, pressures and responses are understood, our ability to predict the impacts of a changing climate on ringed seals will remain limited.Le phoque annelé de l’Arctique circumpolaire (Pusa hispida) occupe son habitat de reproduction sur glace rapide pendant quatre à cinq mois de l’hiver, et la banquise ou les eaux libres adjacentes pendant le reste de l’année. Entre 1971 et 1978 puis entre 1992 et 2019, nous avons échantillonné environ 100 phoques annelés par année dans l’ouest du détroit de Prince- Albert, le principal habitat de reproduction sur glace rapide du phoque annelé dans l’ouest de l’Arctique canadien, adjacent au principal habitat d’alimentation hivernal de l’est du golfe Amundsen. Comme paramètre de mesure de la condition corporelle, nous avons mesuré l’épaisseur du lard ventral du phoque, pour laquelle nous avons appliqué une correction en fonction de la taille du corps. Comme paramètre de reproduction, nous avons mesuré le taux annuel d’ovulation des femelles multipares et le pourcentage de veaux récoltés en eaux libres. Nous avons examiné ces paramètres biologiques par rapport à l’indice d’oscillation arctique hivernal et par rapport au moment du dégagement des glaces de mer dans l’est du golfe Amundsen au printemps. Nous n’avons pas remarqué d’effets importants en ce qui a trait à l’âge ou au mois d’échantillonnage (juin ou juillet) sur l’épaisseur du lard de l’adulte, mais nous avons constaté des effets importants en ce qui a trait au sexe et à l’année, et, chez les femelles, des effets en matière d’ovulation. Entre les séries, comme nous l’avions déjà observé jusqu’en 2011, il y avait une importante tendance temporelle à la baisse sur le plan de l’épaisseur du lard chez les adultes des deux sexes. Il n’y avait pas de tendance temporelle du point de vue de l’épaisseur résiduelle du lard, aucune corrélation entre l’épaisseur du lard et la date du dégagement des glaces de mer dans l’est du golfe Amundsen, et un modèle quasi cyclique du point de vue de l’épaisseur du lard par rapport à certaines phases de l’indice d’oscillation arctique hivernal. Les taux d’ovulation annuels se situaient principalement dans la gamme du 80 % à 100 %, en corrélation avec le pourcentage de veaux de la récolte en eaux libres pendant la même année. Trois des 36 années (1974, 2005, 2012) ont enregistré des échecs de reproduction, lorsque 50 % des femelles multipares n’ont pas ovulé. Dans chaque cas, les taux d’ovulation sont retournés à la normale en un à trois ans. Les faibles taux d’ovulation annuels ont été corrélés avec le dégagement tardif des glaces de mer dans l’est du golfe Amundsen au printemps, deux des grands échecs d’ovulation ayant eu lieu pendant les années où le dégagement printanier des glaces de mer a été retardé de cinq à six semaines. L’échec d’ovulation le plus récent (2012) était différent en ce sens qu’il s’est produit pendant une année moyenne de dégagement des glaces, mais à la fin d’une séquence de six ans d’épaisseurs moyennes résiduelles négatives du lard. Dans le détroit de Prince-Albert, le dégagement plus hâtif des glaces de mer au printemps, d’après un taux observé de 3,8 jours par décennie, ne se traduirait pas, en moyenne, par la perte physique de glaces de mer pour la mise bas des veaux dans cet habitat important avant 2140. Les mécanismes liés à la tendance temporelle soutenue à la baisse de la condition corporelle, le lien avec certaines phases de l’indice d’oscillation arctique hivernal, et les échecs d’ovulation temporaires, mais épisodiques sont complexes et ne s’expliquent pas entièrement par le moment du dégagement des glaces de mer ou par l’indice d’oscillation arctique hivernal. Tant que le mélange complexe de facteurs, de pressions et de réponses ne sera pas compris, notre capacité à prévoir les incidences du changement climatique sur le phoque annelé sera restreinte

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589