Levitated optomechanics with a fiber Fabry-Perot interferometer

In recent years, quantum phenomena have been experimentally demonstrated on variety of optomechanical systems ranging from micro-oscillators to photonic crystals. Since single photon couplings are quite small, most experimental approaches rely on the realization of high finesse Fabry– Perot cavities in order to enhance the effective coupling. Here we show that by exploiting a, long path, lowfinesse fiber Fabry–Perot interferometer ground state cooling can be achieved. We model a 100 m long cavity with a finesse of 10 and analyze the impact of additional noise sources arising from the fiber. As a mechanical oscillator we consider a levitated microdisk but the same approach could be applied to other optomechanical systems

Spin Entanglement Witness for Quantum Gravity

Understanding gravity in the framework of quantum mechanics is one of the great challenges in modern physics. However, the lack of empirical evidence has lead to a debate on whether gravity is a quantum entity. Despite varied proposed probes for quantum gravity, it is fair to say that there are no feasible ideas yet to test its quantum coherent behavior directly in a laboratory experiment. Here, we introduce an idea for such a test based on the principle that two objects cannot be entangled without a quantum mediator. We show that despite the weakness of gravity, the phase evolution induced by the gravitational interaction of two micron size test masses in adjacent matter-wave interferometers can detectably entangle them even when they are placed far apart enough to keep Casimir-Polder forces at bay. We provide a prescription for witnessing this entanglement, which certifies gravity as a quantum coherent mediator, through simple spin correlation measurements

Hybrid Mechanical Systems

We discuss hybrid systems in which a mechanical oscillator is coupled to another (microscopic) quantum system, such as trapped atoms or ions, solid-state spin qubits, or superconducting devices. We summarize and compare different coupling schemes and describe first experimental implementations. Hybrid mechanical systems enable new approaches to quantum control of mechanical objects, precision sensing, and quantum information processing.Comment: To cite this review, please refer to the published book chapter (see Journal-ref and DOI). This v2 corresponds to the published versio

Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Immune-mediated necrotising myopathy is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase concentrations, and autoantibodies recognising 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or the signal recognition particle (SRP). No approved therapies exist for people with immune-mediated necrotising myopathy. Previous studies have suggested that complement activation might be pathogenic in immune-mediated necrotising myopathy; therefore, zilucoplan, a complement C5 (C5) inhibitor, could be a potential therapy. We aimed to evaluate the efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive immune-mediated necrotising myopathy. METHODS: IMNM-01 was a phase 2, multicentre, randomised, double-blind, placebo-controlled study done at 15 hospital sites across the USA, the UK, France, and the Netherlands. Participants aged 18–74 years were eligible for inclusion if they had a clinically confirmed diagnosis of immune-mediated necrotising myopathy, positive serology for anti-HMGCR or anti-SRP autoantibodies, clinical evidence of weakness, serum total creatine kinase concentration of more than 1000 U/L at screening, and no change in glucocorticoids or other immunosuppressive therapies for 30 days before baseline or expected during the first 8 weeks of the study. Participants were randomly assigned (1:1) to receive daily subcutaneous zilucoplan (0·3 mg/kg) or placebo for 8 weeks by use of a computerised randomisation algorithm; with optional enrolment in the study open-label extension. Randomisation was stratified by autoantibody status. Participants and study staff were masked to treatment group assignment. Primary efficacy endpoint (in the intent-to-treat population, defined as all participants who were randomly assigned to a treatment group) was percent change from baseline to week 8 in creatine kinase concentrations. Safety analyses were performed on the safety population (participants who received at least one dose of study drug during the main study, irrespective of whether they continued to the extension period—study participants were analysed on the basis of the treatment received). This study is registered with ClinicalTrials.gov, NCT04025632. FINDINGS: Between Nov 7, 2019, and Jan 7, 2021, we randomly assigned 27 participants (13 female and 14 male) to receive zilucoplan (n=12) or placebo (n=15). All 27 participants completed the 8-week main study. At week 8 there were no significant differences between treatment groups in median percent change of creatine kinase concentrations versus baseline (–15·1% [IQR –31·1 to 3·2] in the zilucoplan group vs –16·3% [–43·8 to 5·9] in the placebo group; p=0·46) and no clinically relevant improvement over time within the treatment group despite target engagement based on mode of action. There were no unexpected adverse safety or tolerability findings. Treatment-emergent adverse events were reported in nine (75%) of 12 participants in the zilucoplan group, and in 13 (87%) of 15 participants in the placebo group, and serious treatment-emergent adverse events were reported in zero participants in the zilucoplan group and three (20%) participants in the placebo group. The most frequent treatment-emergent adverse events were headache (four [33%] participants in the zilucoplan group and four [27%] participants in the placebo group) and nausea (three [25%] participants in the zilucoplan group and three [20%] participants in the placebo group). INTERPRETATION: C5 inhibition does not appear to be an efficacious treatment modality for people with immune-mediated necrotising myopathy. Rather than being the primary driver for disease activity, complement activation might be secondary to muscle injury. FUNDING: Ra Pharmaceuticals (now part of UCB Pharma)

Panic disorder and locomotor activity

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A three month controlled intervention of intermittent whole body vibration designed to improve functional ability and attenuate bone loss in patients with rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune condition that results in pain and disability. Patients with RA have a decreased functional ability and are forced into a sedentary lifestyle and as such, these patients often become predisposed to poor bone health. Patients with RA may also experience a decreased health related quality of life (HRQoL) due to their disease. Whole body vibration (WBV) is a form of exercise that stimulates bone loading through forced oscillation. WBV has also been shown to decrease pain and fatigue in other rheumatic diseases, as well as to increase muscle strength. This paper reports on the development of a semi randomised controlled clinical trial to assess the impact of a WBV intervention aiming to improve functional ability, attenuate bone loss, and improve habitual physical activity levels in patients with RA. Methods/Design: This study is a semi randomised, controlled trial consisting of a cohort of patients with established RA assigned to either a WBV group or a CON (control) group. Patients in the WBV group will undergo three months of twice weekly intermittent WBV sessions, while the CON group will receive standard care and continue with normal daily activities. All patients will be assessed at baseline, following the three month intervention, and six months post intervention. Main outcomes will be an improvement in functional ability as assessed by the HAQ. Secondary outcomes are attenuation of loss of bone mineral density (BMD) at the hip and changes in RA disease activity, HRQoL, habitual physical activity levels and body composition. Discussion: This study will provide important information regarding the effects of WBV on functional ability and BMD in patients with RA, as well as novel data regarding the potential changes in objective habitual physical activity patterns that may occur following the intervention. The sustainability of the intervention will also be assessed

Memory for medication side effects in younger and older adults: the role of subjective and objective importance

Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age

Differential impact of LPG-and PG-deficient Leishmania major mutants on the immune response of human dendritic cells

<div><p>Background</p><p><i>Leishmania major</i> infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of <i>Leishmania</i> parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.</p><p>Methodology/Principal Findings</p><p>Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating <i>L</i>. <i>major</i> Friedlin V1 mutants defective in LPG alone, (FV1 <i>lpg1-</i>), or generally deficient for all PGs, (FV1 <i>lpg2-</i>). Infection with metacyclic, infective stage, <i>L</i>. <i>major</i> or purified LPG induced high levels of <i>IL12B</i> subunit gene transcripts in hDCs, which was abrogated with FV1 <i>lpg1-</i> infections. In contrast, hDC infections with FV1 <i>lpg2-</i> displayed increased <i>IL12B</i> expression, suggesting other PG-related/<i>LPG2</i> dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 <i>lpg1-</i>, FV1 <i>lpg2-</i> infections revealed that FV1 <i>lpg1-</i> mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription.</p><p>Conclusions/Significance</p><p>These data suggest that <i>L</i>. <i>major</i> LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring <i>Leishmania</i> surface glycoconjugates that result in modulation of host cellular IL12.</p></div

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base

Tests of chameleon gravity

Theories of modified gravity, where light scalars with non-trivial self-interactions and non-minimal couplings to matter—chameleon and symmetron theories—dynamically suppress deviations from general relativity in the solar system. On other scales, the environmental nature of the screening means that such scalars may be relevant. The highly-nonlinear nature of screening mechanisms means that they evade classical fifth-force searches, and there has been an intense effort towards designing new and novel tests to probe them, both in the laboratory and using astrophysical objects, and by reinterpreting existing datasets. The results of these searches are often presented using different parametrizations, which can make it difficult to compare constraints coming from different probes. The purpose of this review is to summarize the present state-of-the-art searches for screened scalars coupled to matter, and to translate the current bounds into a single parametrization to survey the state of the models. Presently, commonly studied chameleon models are well-constrained but less commonly studied models have large regions of parameter space that are still viable. Symmetron models are constrained well by astrophysical and laboratory tests, but there is a desert separating the two scales where the model is unconstrained. The coupling of chameleons to photons is tightly constrained but the symmetron coupling has yet to be explored. We also summarize the current bounds on f(R) models that exhibit the chameleon mechanism (Hu and Sawicki models). The simplest of these are well constrained by astrophysical probes, but there are currently few reported bounds for theories with higher powers of R. The review ends by discussing the future prospects for constraining screened modified gravity models further using upcoming and planned experiments