Evolution in controls methods for the SPS power converters

In common with much accelerator specific material, there is a constant need to improve both hardware and software for power converter control. Maintenance and performance improvements of older systems have become extremely tedious and in some areas impossible. By using modern real-time software and the latest high-performance processors, such problems should be substantially reduced. This paper describes the software concepts and the hardware chosen for the upgrade of the existing facilities. Using the UNIX compatible LynxOS real time kernel, running on a PowerPC 603 in a VME environment, this new approach provides excellent performance while retaining the desired flexibility for future enhancements. The 64 channel system is implemented as a set of cooperating processes, several of which are multi-threaded. Processes include analogue function generation, analogue measurement and digital I/O, all of which are accurately scheduled by the accelerator timing system. This generalised structure, which performs complex sequences of operations is described in detail, as well as how it can be adapted to a wide variety of accelerator tasks

The All-digital Approach to LHC Power Converter Current Control

The design of the LHC machine imposes severe demands upon the control of current in the 1700 magnet circuits. This has required the use of novel methods for the control of individual power converters and of the magnet current control system as a whole. This paper will review the chosen hardware and software methods and architectures. The digital regulation techniques used to achieve the overall targets for short-term stability (<3ppm) and reproducibility (<10ppm) of the 24 principal LHC circuits will be discussed. While the proposed system architecture will follow the canonical three-layer design, so successfully exploited in LEP, the software will be far from traditional. This software must be more reliable and maintainable than ever before, and will need to integrate with advanced object-oriented applications via commercial middleware. These challenges will be faced by applying object-oriented techniques throughout the system and by harnessing the power of XML for system definition

Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings [version 2; peer review: 2 approved]

Global health pandemics, such as coronavirus disease 2019 (COVID19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent in-vitro and in-silico work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment. In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs. Well conducted, adaptive platform trials utilising a multi-arm multistage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial. The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for each further wave of COVID-19, and enable preparedness for future global health pandemics

Adaptive platform trials using multi-arm, multi-stage protocols: getting fast answers in pandemic settings [version 1; peer review: 2 approved]

Global health pandemics, such as coronavirus disease 2019 (COVID-19), require efficient and well-conducted trials to determine effective interventions, such as treatments and vaccinations. Early work focused on rapid sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), subsequent in-vitro and in-silico work, along with greater understanding of the different clinical phases of the infection, have helped identify a catalogue of potential therapeutic agents requiring assessment. In a pandemic, there is a need to quickly identify efficacious treatments, and reject those that are non-beneficial or even harmful, using randomised clinical trials. Whilst each potential treatment could be investigated across multiple, separate, competing two-arm trials, this is a very inefficient process. Despite the very large numbers of interventional trials for COVID-19, the vast majority have not used efficient trial designs. Well conducted, adaptive platform trials utilising a multi-arm multi-stage (MAMS) approach provide a solution to overcome limitations of traditional designs. The multi-arm element allows multiple different treatments to be investigated simultaneously against a shared, standard-of-care control arm. The multi-stage element uses interim analyses to assess accumulating data from the trial and ensure that only treatments showing promise continue to recruitment during the next stage of the trial. The ability to test many treatments at once and drop insufficiently active interventions significantly speeds up the rate at which answers can be achieved. This article provides an overview of the benefits of MAMS designs and successes of trials, which have used this approach to COVID-19. We also discuss international collaboration between trial teams, including prospective agreement to synthesise trial results, and identify the most effective interventions. We believe that international collaboration will help provide faster answers for patients, clinicians, and health care systems around the world, including for future waves of COVID-19, and enable preparedness for future global health pandemics

Evaluation of subcutaneous proleukin (Interleukin-2) in a randomized international trial (ESPRIT): Geographical and gender differences in the baseline characteristics of participants

Background: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells ≥300 cells/μL. Objectives: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. Method: Baseline characteristics of randomized participants were summarized by region. Results: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/μL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). Conclusion: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability

The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies

BACKGROUND Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. METHODS Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified. RESULTS In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3(rd) versus 1(st) tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3(rd) versus 1(st) tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only. CONCLUSIONS In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome

‘Blood, guts and Bambi eyes’ : Urotsukidoji and the Transcultural Reception and Regulation of Anime

The regulation and reception of anime in Britain has, historically, been fraught with difficulty. In 1992, the British Board of Film Classification (BBFC) rejected the first instalment of Urotsukidoji, a controversial series of erotic anime, on the grounds of its sexually explicit content; this decision set a precedent for the way in which they would continue to censor anime for the following two decades. Nearly twenty years later, in 2009, Clause 62 of the Coroners and Justice Act, also colloquially known as the ‘Dangerous Cartoons Act’, made it a criminal offence to possess non-photographic pornographic images of children, including CGI, cartoons, manga images and drawings. Through an examination of the BBFC's archival materials on Urotsukidoji – Legend of the Overfiend, supplemented by references to a small number of newspaper articles published during this period, this article offers a range of insights into the historical context in which the current series of debates surrounding the ‘Dangerous Cartoons Act’ can be situated and assessed. These are used to consider the transcultural flow of genres across national borders, and the difficulties that a regulator from one culture encounters when dealing with controversial material originating from another, such as Japan, that has a substantially different set of social values and artistic conventions. Furthermore, this case highlights the important role played by distribution companies in shaping the production and evolution of genres within the transcultural marketplace

Carbon and nitrogen fixation and metabolite exchange in and between individual cells of Anabaena oscillarioides

Filamentous nitrogen fixing cyanobacteria are key players in global nutrient cycling, but the relationship between CO"2- and N"2-fixation and intercellular exchange of these elements remains poorly understood in many genera. Using high-resolution nanometer-scale secondary ion mass spectrometry (NanoSIMS) in conjunction with enriched H13CO"3- and 15N"2 incubations of Anabaena oscillarioides, we imaged the cellular distributions of C, N and P and 13C and 15N enrichments at multiple time points during a diurnal cycle as proxies for C and N assimilation. The temporal and spatial distributions of the newly fixed C and N were highly heterogeneous at both the intra- and inter-cellular scale, and indicative of regions performing active assimilation and biosynthesis. Subcellular components such as the neck region of heterocycts, cell division septae and putative cyanophycin granules were clearly identifiable by their elemental composition. Newly fixed nitrogen was rapidly exported from heterocysts and was evenly allocated among vegetative cells, with the exception of the most remote vegetative cells between heterocysts, which were N limited based on lower 15N enrichment. Preexisting functional heterocysts had the lowest levels of 13C and 15N enrichment, while heterocysts that were inferred to have differentiated during the experiment had higher levels of enrichment. This innovative approach, combining stable isotope labeling and NanoSIMS elemental and isotopic imaging, allows characterization of cellular development (division, heterocyst differentiation), changes in individual cell composition and cellular roles in metabolite exchange

Confirmatory Factor Analysis of the Pain Care Quality Surveys (Pain CQ © )

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/1/hesr12014-sup-0001-Author_matrix.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98233/2/hesr12014.pd