306 research outputs found

    Using Atom Interferometery to Search for New Forces

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    Atom interferometry is a rapidly advancing field and this Letter proposes an experiment based on existing technology that can search for new short distance forces. With current technology it is possible to improve the sensitivity by up to a factor of 10^2 and near-future advances will be able to rewrite the limits for forces with ranges from 100 um to 1 km.Comment: 5 pages, 2 figure

    Electrohysterography. A promising alternative for monitoring contractions

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    Monitoring contractions during labour using the external tocodynamometer can be difficult or even impossible, and using the invasive intrauterine pressure catheter is associated with rare but serious complications. A new non-invasive technique is currently available: electrohysterography (EHG). This technique converts the electrical activity of the uterine muscle into a legible tocogram. The EHG signal has a high correlation with the intrauterine pressure and provides a more accurate assessment of uterine activity compared to external tocodynamometry. EHG is suitable for women in labour with failure of the external tocodynamometer. In clinical practice EHG also appeared to report a more detailed tocographic waveform, like hypertonia or unorganized electrical uterine activity. However, its signal quality depends on adequate skin preparation and correct positioning of the electrodes on the maternal abdomen. Hence, with electrohysterography as noninvasive alternative for uterine monitoring, choosing between safety and accuracy is no longer necessary. Conflict of interest and financial support: ICMJE forms provided by the authors are available online along with the full text of this article.</p

    Suppression of HBV by Tenofovir in HBV/HIV coinfected patients : a systematic review and meta-analysis

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    Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains. Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine. Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare. Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone

    Hepatic fibrosis and immune phenotype vary by HCV viremia in HCV/HIV co-infected subjects: A Women\u27s interagency HIV study.

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    HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear. In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI). We found liver fibrosis (APRI) was 50% lower in Elites and ARTc compared to ARTuc. Higher liver fibrosis was associated with significantly low CD4+ T cell counts (P \u3c 0.001, coefficient r = −0.463). Immune activation varied by HIV phenotype but was not modified by HCV viremia. HCV viremia was associated with elevated CD8 T-cell Caspase-3 in Elites, ARTuc, and HIV− except ARTc. CD8 T-cell Caspase-3 levels were significantly higher in HCV RNA+ Elites (P = 0.04) and ARTuc (P = 0.001) and HIV− groups (P = 0.02) than ARTc. Importantly, ARTuc HCV RNA+ had significantly higher CD4 T-cell interleukin-17 levels than ARTuc HCV RNA− (P = 0.005). HIV control was associated with lower liver fibrosis in HCV/HIV co-infected women. HCV viremia is associated with an inflammatory CD4 TH-17 phenotype in absence of HIV control and higher frequency of pro-apoptosis CD8 T-cells critical to avert progression of HIV and HCV disease that is attenuated in ART controllers. Elite controllers with HCV viremia are more prone to CD8 T-cell apoptosis than ART controllers, which could have negative consequences over time, highlighting the importance of ART control in HCV/HIV coinfected individuals

    The effect of HIV infection and HCV viremia on Inflammatory Mediators and Hepatic Injury-The Women\u27s Interagency HIV Study.

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    Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18), ART-treated HIV-controlled (ARTc, n = 20), uncontrolled on anti-retroviral therapy (ARTuc, n = 21) and elite HIV controllers (Elite, n = 20). All were HCV seroreactive and had either resolved (HCV RNA-; \u3c50IU/mL) or had chronic HCV infection (HCV RNA+). In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI) was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection

    Is complexity leadership theory complex enough? A critical appraisal, some modifications and suggestions for further research

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    Scholars are increasingly seeking to develop theories that explain the underlying processes whereby leadership is enacted. This shifts attention away from the actions of ‘heroic’ individuals and towards the social contexts in which people with greater or lesser power influence each other. A number of researchers have embraced complexity theory, with its emphasis on non-linearity and unpredictability. However, some complexity scholars still depict the theory and practice of leadership in relatively non-complex terms. They continue to assume that leaders can exercise rational, extensive and purposeful influence on other actors to a greater extent than is possible. In effect, they offer a theory of complex organizations led by non-complex leaders who establish themselves by relatively non-complex means. This testifies to the enduring power of ‘heroic’ images of leader agency. Without greater care, the terminology offered by complexity leadership theory could become little more than a new mask for old theories that legitimize imbalanced power relationships in the workplace. This paper explores how these problems are evident in complexity leadership theory, suggests that communication and process perspectives help to overcome them, and outlines an agenda for further research on these issues

    Chronic Hepatitis B Finite Treatment: similar and different concerns with new drug classes

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    Chronic hepatitis B, a major cause of liver disease and cancer, affects over 250 million people worldwide. Currently there is no cure, only suppressive therapies. Efforts to develop finite curative HBV therapies are underway, consisting of combinations of multiple novel agents +/- nucleos(t)ide reverse transcriptase inhibitors. The HBV Forum convened a webinar in July 2021, and subsequent working group discussions to address how and when to stop finite therapy for demonstration of sustained off-treatment efficacy and safety responses. Participants included leading experts in academia, clinical practice, pharmaceutical companies, patient representatives and regulatory agencies. This Viewpoint outlines areas of consensus within our multi-stakeholder group for stopping finite therapies in chronic Hepatitis B investigational studies, including trial design, patient selection, outcomes, biomarkers, pre-defined stopping criteria, pre-defined retreatment criteria, duration of investigational therapies, and follow up after stopping therapy. Future research of unmet needs are discussed

    Syndromic approach to arboviral diagnostics for global travelers as a basis for infectious disease surveillance

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    Background Arboviruses have overlapping geographical distributions and can cause symptoms that coincide with more common infections. Therefore, arbovirus infections are often neglected by travel diagnostics. Here, we assessed the potential of syndrome-based approaches for diagnosis and surveillance of neglected arboviral diseases in returning travelers. Method To map the patients high at risk of missed clinical arboviral infections we compared the quantity of all arboviral diagnostic requests by physicians in the Netherlands, from 2009 through 2013, with a literature-based assessment of the travelers’ likely exposure to an arbovirus. Results 2153 patients, with travel and clinical history were evaluated. The diagnostic assay for dengue virus (DENV) was the most commonly requested (86%). Of travelers returning from Southeast Asia with symptoms compatible with chikungunya virus (CHIKV), only 55% were tested. For travelers in Europe, arbovirus diagnostics were rarely requested. Over all, diagnostics for most arboviruses were requested only on severe clinical presentation. Conclusion Travel destination and syndrome were used inconsistently for triage of diagnostics, likely resulting in vast under-diagnosis of arboviral infections of public health significance. This study shows the need for more awareness among physicians and standardization of syndromic diagnostic algorithm
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