Robust superconductivity and fragile magnetism induced by the strong Cu impurity scattering in the high-pressure phase of FeSe

Superconductivity in FeSe is strongly enhanced under applied pressure and it is proposed to emerge from anomalously coupled structural and magnetic phases. Small impurities inside the Fe plane can strongly disrupt the pair formation in FeSe at ambient pressure and can also reveal the interplay between normal and superconducting phases. Here, we investigate how an impurity inside the Fe plane induced by the Cu substitution can alter the balance between competing electronic phases of FeSe at high pressures. In the absence of an applied magnetic field, at low pressures the nematic and superconducting phases are suppressed by a similar factor. On the other hand, at high pressures, above 10 kbar, the superconductivity remains unaltered despite the lack of any signature in transport associated to a magnetic phase in zero-magnetic field. However, by applying a magnetic field, the resistivity displays an anomaly preceding the activated behaviour in temperature, assigned to a magnetic anomaly. We find that the high-pressure superconducting phase of FeSe is robust and remains enhanced in the presence of Cu impurity, whereas the magnetic phase is not. This could suggest that high-$T_{\rm c}$ superconductivity has a sign-preserving order parameter in a presence of a rather glassy magnetic phase.Comment: 13 pages, 9 figure

Dialogue based interfaces for universal access.

Conversation provides an excellent means of communication for almost all people. Consequently, a conversational interface is an excellent mechanism for allowing people to interact with systems. Conversational systems are an active research area, but a wide range of systems can be developed with current technology. More sophisticated interfaces can take considerable effort, but simple interfaces can be developed quite rapidly. This paper gives an introduction to the current state of the art of conversational systems and interfaces. It describes a methodology for developing conversational interfaces and gives an example of an interface for a state benefits web site. The paper discusses how this interface could improve access for a wide range of people, and how further development of this interface would allow a larger range of people to use the system and give them more functionality

Multiband description of the upper critical field of bulk FeSe

The upper critical field of multiband superconductors can be an essential quantity to unravel the nature of superconducting pairing and its interplay with the electronic structure. Here we experimentally map out the complete upper critical field phase diagram of FeSe for different magnetic field orientations at temperatures down to 0.3 K using both resistivity and torque measurements. The temperature dependence of the upper critical field reflects that of a multiband superconductor and requires a two-band description in the clean limit with band coupling parameters favoring interband over intraband interactions. Despite the relatively small Maki parameter in FeSe of α ∼ 1.6, the multiband description of the upper critical field is consistent with the stabilization of a Fulde-Ferrell-Larkin-Ovchinnikov state below T /Tc ∼ 0.3. We find that the anomalous behavior of the upper critical field is linked to a departure from the single-band picture, and FeSe provides a clear example of where multiband effects and the strong anisotropy of the superconducting gap need to be taken into account

A systematic review of biomarkers for disease progression in Parkinson's disease

This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124).BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.Publisher PDFPeer reviewe

Anomalous high-magnetic field electronic state of the nematic superconductors FeSe₁₋ₓSₓ

Understanding superconductivity requires detailed knowledge of the normal electronic state from which it emerges. A nematic electronic state that breaks the rotational symmetry of the lattice can potentially promote unique scattering relevant for superconductivity. Here, we investigate the normal transport of superconducting FeSe1−xSx across a nematic phase transition using high-magnetic fields up to 69 T to establish the temperature and field dependencies. We find that the nematic state is dominated by a linear resistivity at low temperatures that evolves towards Fermi-liquid behavior, depending on the composition x and the impurity level. Near the nematic end point, we find an extended temperature regime with ∼T1.5 resistivity, different from the behavior found near an antiferromagnetic critical point. The variation of the resistivity exponent with temperature reflects the importance of the nematoelastic coupling that can also suppress divergent critical fluctuations at the nematic end point. The transverse magnetoresistance inside the nematic phase has a ∼H1.55 dependence over a large magnetic field range and it displays an unusual peak at low temperatures inside the nematic phase. Our study reveals anomalous transport inside the nematic phase, influenced by both changes in the electronic structure and the scattering with the lattice and spin fluctuations

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial

\ua9 2022 American Medical Association. All rights reserved.Importance: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective: To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants: This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions: Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures: The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results: Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P =.006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance: In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration: ISRCTN Identifier: 16108482

Temperature drives variation in flying insect biomass across a German malaise trap network

1. Among the many concerns for biodiversity in the Anthropocene, recent reports of flying insect loss are particularly alarming, given their importance as pollinators, pest control agents, and as a food source. Few insect monitoring programmes cover the large spatial scales required to provide more generalizable estimates of insect responses to global change drivers. 2. We ask how climate and surrounding habitat affect flying insect biomass using data from the first year of a new monitoring network at 84 locations across Germany comprising a spatial gradient of land cover types from protected to urban and crop areas. 3. Flying insect biomass increased linearly with temperature across Germany. However, the effect of temperature on flying insect biomass flipped to negative in the hot months of June and July when local temperatures most exceeded long-term averages. 4. Land cover explained little variation in insect biomass, but biomass was lowest in forests. Grasslands, pastures, and orchards harboured the highest insect biomass. The date of peak biomass was primarily driven by surrounding land cover, with grasslands especially having earlier insect biomass phenologies. 5. Standardised, large-scale monitoring provides key insights into the underlying processes of insect decline and is pivotal for the development of climate-adapted strategies to promote insect diversity. In a temperate climate region, we find that the positive effects of temperature on flying insect biomass diminish in a German summer at locations where temperatures most exceeded long-term averages. Our results highlight the importance of local adaptation in climate change-driven impacts on insect communities

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial.

Importance: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective: To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants: This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions: Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures: The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results: Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance: In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration: ISRCTN Identifier: 16108482

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial aimed to determine whether or not oral Δ(9)-tetrahydrocannabinol (Δ(9)-THC) slowed the course of progressive multiple sclerosis (MS); evaluate safety of cannabinoid administration; and, improve methods for testing treatments in progressive MS.The National Institute for Health Research Health Technology Assessment programmeMedical Research Council Efficacy and Mechanism Evaluation programmeMultiple Sclerosis SocietyMultiple Sclerosis Trus

Standing up in Multiple Sclerosis (SUMS): Protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

This study is funded by the NIHR Health Technology Assessment Programme (14/176/12), United Kingdom.Background:  Impaired mobility is a cardinal feature of multiple sclerosis (MS) and is rated by people with MS as their highest priority. By the secondary progressive phase, balance, mobility and physical activity levels are significantly compromised; an estimated 70% of people with secondary progressive MS fall regularly. Our ongoing research has systematically developed ‘Balance Right in MS’ (BRiMS), an innovative, manualised 13-week guided self-management programme tailored to the needs of people with MS, designed to improve safe mobility and minimise falls. Our eventual aim is to assess the clinical and cost effectiveness of BRiMS in people with secondary progressive MS by undertaking an appropriately statistically powered, multi-centre, assessor-blinded definitive, randomised controlled trial. This feasibility study will assess the acceptability of the intervention and test the achievability of running such a definitive trial. Methods/design:  This is a pragmatic multi-centre feasibility randomised controlled trial with blinded outcome assessment. Sixty ambulant people with secondary progressive MS who self-report two or more falls in the previous 6 months will be randomly allocated (1:1) to either the BRiMS programme plus usual care or to usual care alone. All participants will be assessed at baseline and followed up at 15 weeks and 27 weeks post-randomisation. The outcomes of this feasibility trial include: • Feasibility outcomes, including trial recruitment, retention and completion • Assessment of the proposed outcome measures for the anticipated definitive trial (including measures of walking, quality of life, falls, balance and activity level) • Measures of adherence to the BRiMS programme • Data to inform the economic evaluation in a future trial • Process evaluation (assessment of treatment fidelity and qualitative evaluation of participant and treating therapist experience) Discussion:  The BRiMS intervention aims to address a key concern for MS service users and providers. However, there are several uncertainties which need to be addressed prior to progressing to a full-scale trial, including acceptability of the BRiMS intervention and practicality of the trial procedures. This feasibility trial will provide important insights to resolve these uncertainties and will enable a protocol to be finalised for use in the definitive trial.Publisher PDFPeer reviewe