Charting and comparing Tunisia's, Algeria's, Morocco's and Mauritania's political development over the past 10 years, this book offers fresh and original insight into their contrasting experiences as ...well as extending Levitsky and Way's model.
Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in ...mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.
Musculoskeletal pain, the most common cause of disability globally, is most frequently managed in primary care. People with musculoskeletal pain in different body regions share similar ...characteristics, prognosis, and may respond to similar treatments. This overview aims to summarise current best evidence on currently available treatment options for the five most common musculoskeletal pain presentations (back, neck, shoulder, knee and multi-site pain) in primary care.
A systematic search was conducted. Initial searches identified clinical guidelines, clinical pathways and systematic reviews. Additional searches found recently published trials and those addressing gaps in the evidence base. Data on study populations, interventions, and outcomes of intervention on pain and function were extracted. Quality of systematic reviews was assessed using AMSTAR, and strength of evidence rated using a modified GRADE approach.
Moderate to strong evidence suggests that exercise therapy and psychosocial interventions are effective for relieving pain and improving function for musculoskeletal pain. NSAIDs and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects need careful consideration. Corticosteroid injections were found to be beneficial for short-term pain relief among patients with knee and shoulder pain. However, current evidence remains equivocal on optimal dose, intensity and frequency, or mode of application for most treatment options.
This review presents a comprehensive summary and critical assessment of current evidence for the treatment of pain presentations in primary care. The evidence synthesis of interventions for common musculoskeletal pain presentations shows moderate-strong evidence for exercise therapy and psychosocial interventions, with short-term benefits only from pharmacological treatments. Future research into optimal dose and application of the most promising treatments is needed.
Summary Background WHO estimates that a third of the world's population has latent tuberculosis infection and that less than 5% of those infected are diagnosed and treated to prevent tuberculosis. We ...aimed to systematically review studies that report the steps from initial tuberculosis screening through to treatment for latent tuberculosis infection, which we call the latent tuberculosis cascade of care. We specifically aimed to assess the number of people lost at each stage of the cascade. Methods We did a systematic review and meta-analysis of study-level observational data. We searched MEDLINE (via OVID), Embase, and Health Star for observational studies, published between 1946 and April 12, 2015, that reported primary data for diagnosis and treatment of latent tuberculosis infection. We did meta-analyses using random and fixed effects analyses to identify percentages of patients with latent tuberculosis infection completing each step in the cascade. We also estimated pooled proportions in subgroups stratified by different characteristics of interest to assess risk factors for losses. Results We identified 58 studies, describing 70 distinct cohorts and 748 572 people. Steps in the cascade associated with greater losses included completion of testing (71·9% 95% CI 71·8–72·0 of people intended for screening), completion of medical evaluation (43·7% 42·5–44·9), recommendation for treatment (35·0% 33·8–36·4), and completion of treatment if started (18·8% 16·3–19·7). Steps with fewer losses included receiving test results, referral for evaluation if test positive, and accepting to start therapy if recommended. Factors associated with fewer losses were immune-compromising medical indications, being part of contact investigations, and use of rifamycin-based regimens. Interpretation We identify major losses at several steps in the cascade of care for latent tuberculosis infection. Improvements in management of latent tuberculosis will need programmatic approaches to address the losses at each step in the cascade. Funders Canadian Institutes of Health Research.
High surface area porous n-type WO3 electrodes were prepared electrochemically and used as a photoanode in a water-splitting photoelectrochemical cell. Various electrolytes containing different ...anions (acetate, chloride, phosphate, perchlorate, and sulfate) and cations (Li+, Na+, and K+) were prepared at pH 1, 3, and 5 to investigate how these anions and cations affect the efficiency of the photo-oxidation reaction of water on the WO3 surface. To quantitatively compare their effects on O2 evolution, photocurrent to oxygen conversion efficiency was obtained for each electrolyte by simultaneously measuring photocurrent and O2 produced in a sealed divided cell. The type of competing reactions present in each electrolyte and their effects on water oxidation to O2 or to hydrogen peroxide, which is known to accumulate on the WO3 surface and cause photocorrosion, were investigated. The results reported in this study will be useful in formulating optimum electrolyte compositions to enhance desired photo-oxidation reactions for various photoelectrochemical cells.
A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic ...effects.
In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels.
Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval CI, -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events.
The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).
In the scale-up of quantum computers, the framework underpinning fault-tolerance generally relies on the strong assumption that environmental noise affecting qubit logic is uncorrelated (Markovian). ...However, as physical devices progress well into the complex multi-qubit regime, attention is turning to understanding the appearance and mitigation of correlated - or non-Markovian - noise, which poses a serious challenge to the progression of quantum technology. This error type has previously remained elusive to characterisation techniques. Here, we develop a framework for characterising non-Markovian dynamics in quantum systems and experimentally test it on multi-qubit superconducting quantum devices. Where noisy processes cannot be accounted for using standard Markovian techniques, our reconstruction predicts the behaviour of the devices with an infidelity of 10
. Our results show this characterisation technique leads to superior quantum control and extension of coherence time by effective decoupling from the non-Markovian environment. This framework, validated by our results, is applicable to any controlled quantum device and offers a significant step towards optimal device operation and noise reduction.
Electrochemical synthesis methods were developed to produce CuBi2O4, a promising p-type oxide for use in solar water splitting, as high surface area electrodes with uniform coverage. These methods ...involved electrodepositing nanoporous Cu/Bi films with a Cu:Bi ratio of 1:2 from dimethyl sulfoxide or ethylene glycol solutions, and thermally oxidizing them to CuBi2O4 at 450 °C in air. Ag-doped CuBi2O4 electrodes were also prepared by adding a trace amount of Ag+ in the plating medium and codepositing Ag with the Cu/Bi films. In the Ag-doped CuBi2O4, Ag+ ions substitutionally replaced Bi3+ ions and increased the hole concentration in CuBi2O4. As a result, photocurrent enhancements for both O2 reduction and water reduction were achieved. Furthermore, while undoped CuBi2O4 electrodes suffered from anodic photocorrosion during O2 reduction due to poor hole transport, Ag-doped CuBiO4 effectively suppressed anodic photocorrosion. The flat-band potentials of CuBi2O4 and Ag-doped CuBi2O4 electrodes prepared in this study were found to be more positive than 1.3 V vs RHE in a 0.1 M NaOH solution (pH 12.8), which make these photocathodes highly attractive for use in solar hydrogen production. The optimized CuBi2O4/Ag-doped CuBi2O4 photocathode showed a photocurrent onset for water reduction at 1.1 V vs RHE, achieving a photovoltage higher than 1 V for water reduction. The thermodynamic feasibility of photoexcited electrons in the conduction band of CuBi2O4 to reduce water was also confirmed by detection of H2 during photocurrent generation. This study provides new understanding for constructing improved CuBi2O4 photocathodes by systematically investigating photocorrosion as well as photoelectrochemical properties of high-quality CuBi2O4 and Ag-doped CuBi2O4 photoelectrodes for photoreduction of both O2 and water.
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