Microscopic dynamics in liquid metals: the experimental point of view

The experimental results relevant for the understanding of the microscopic dynamics in liquid metals are reviewed, with special regards to the ones achieved in the last two decades. Inelastic Neutron Scattering played a major role since the development of neutron facilities in the sixties. The last ten years, however, saw the development of third generation radiation sources, which opened the possibility of performing Inelastic Scattering with X rays, thus disclosing previously unaccessible energy-momentum regions. The purely coherent response of X rays, moreover, combined with the mixed coherent/incoherent response typical of neutron scattering, provides enormous potentialities to disentangle aspects related to the collectivity of motion from the single particle dynamics. If the last twenty years saw major experimental developments, on the theoretical side fresh ideas came up to the side of the most traditional and established theories. Beside the raw experimental results, therefore, we review models and theoretical approaches for the description of microscopic dynamics over different length-scales, from the hydrodynamic region down to the single particle regime, walking the perilous and sometimes uncharted path of the generalized hydrodynamics extension. Approaches peculiar of conductive systems, based on the ionic plasma theory, are also considered, as well as kinetic and mode coupling theory applied to hard sphere systems, which turn out to mimic with remarkable detail the atomic dynamics of liquid metals. Finally, cutting edges issues and open problems, such as the ultimate origin of the anomalous acoustic dispersion or the relevance of transport properties of a conductive systems in ruling the ionic dynamic structure factor are discussed.Comment: 53 pages, 41 figures, to appear in "The Review of Modern Physics". Tentatively scheduled for July issu

'I found myself a despicable being!':Medical students face disturbing moral dilemmas

CONTEXT: The psychological realm of medical students` moral experiences is explored tangentially in medical education literature, often in the context of ethics or professionalism education. This study deepens our understanding by (1) investigating the nature of moral dilemmas experienced at the onset of clinical practice, (2) exploring students` emotional response to these dilemmas, and (3) examining how students perceive the influence of these dilemmas on their professional development. METHODS: This is a cross-sectional qualitative study carried out in 2017 that applied Thematic Template Analysis to individual interviews performed with last-year medical students. The interviews followed the drawing of a Rich Picture representing moral dilemmas experienced by medical students at the onset of clinical practice. RESULTS: Moral dilemmas have four intertwined dimensions. The first relates to students` struggle to prioritize, balance and apply conflicting moral values; the second comprises the clash between students` inner motivation and the external constraints that limit the moral action; the third refers to the conflict between students' current attitudes with the desired/idealized attitudes of the doctor they intend to become; the forth corresponds to weighting conflicting ethical principles during the moral decision. Students` emotional responses are intense, long-lasting, and with a remarkable residue effect, particularly when the moral decision does not align with their moral beliefs. Moral dilemmas are impactful experiences that affect the professional development of medical students and can culminate in both detachment or growth in moral courage. CONCLUSION: Moral dilemmas are memorable, complex, and emotionally intense experiences that impact the professional development of medical students. Understanding students` moral dilemmas can help educators to devise pedagogical activities to anticipate and reflect on these experiences. These activities should happen under the guidance of a non-judgmental facilitator, capable of listening and legitimating students' thoughts and feelings while providing insights to nurture their professional development

Effects of oxidized lipids (4,5 (E)-epoxy-2(E)-heptenal and 4,5 (E)-epoxy-2 (E) -decenal) and lysine reaction products on zinc and calcium utilization: assays in Caco-2 cells

The influence of the presence of brown products from the reaction between two oxidized lipids (4,5 (E)-epoxy-2(E)-heptenal, EH, and 4,5 (E)-epoxy-2 (E)-decenal, ED) and lysine (EH-L and ED-L) on zinc and calcium utilization was studied, and compared with a fructosyl-lysine mixture (F-L). Assays were carried out in Caco-2 cells grown in bicameral chambers. The Zn transported across the cell monolayer was significantly lower in the presence of the EH-L, ED-L and F-L samples, specially with EH-L. Significant decreases in Zn uptake were also observed, with no differences between samples. However, calcium transport was not modified. Thus, the assayed lipid-aminoacid brown products seem to have negative effects on Zn availability, whereas Ca availability appears to be unaffected.Se estudió la influencia de la presencia de productos obtenidos en la reacción de dos lípidos oxidados (4,5(E)-epoxy-2(E)- heptenal, EH, y 4,5(E)-epoxy-2(E)-decenal, ED) con el aminoácido lisina (EH-L y ED-L), sobre la absorción de zinc y calcio, comparándolos frente a una mezcla de fructosil-lisina (F-L). Los ensayos se realizaron con células Caco-2 sembradas en placas bicamerales. La adición de las muestras EH-L, ED-L y F-L al medio de cultivo supuso una reducción significativa en el Zn transportado a través de la monocapa de células, mucho más marcada ante la presencia de EH-L. También se redujo significativamente la captación celular de Zn, sin diferencias entre las distintas muestras ensayadas. Sin embargo, el transporte de Ca no se vio modificado. Por lo tanto, los productos pardos lípido-aminoacídicos ensayados parecen afectar negativamente la disponibilidad del Zn, sin tener efectos notables sobre la del Ca.Peer reviewe

A directly comparative two-gate case-control diagnostic accuracy study of the pure tone screen and HearCheck Screener tests for identifying hearing impairment in school children

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjectives This study directly compared the accuracy of two audiometry-based tests for screening school children for hearing impairment: the currently used test, pure tone screen and a device newly applied to children, HearCheck Screener. Design Two-gate case–control diagnostic test accuracy study. Setting and participants Hearing impaired children (‘intended cases’) aged 4–6 years were recruited between February 2013 and August 2014 from collaborating audiology services. Children with no previously identified impairment (‘intended controls’) were recruited from Foundation and Year 1 of schools between February 2013 and June 2014 in central England. The reference standard was pure tone audiometry. Tests were administered at Nottingham Hearing Biomedical Research Unit or, for some intended cases only, in the participant’s home. Main outcome measures Sensitivity and specificity of the pure tone screen and HearCheck tests based on pure tone audiometry result as reference standard. Results 315 children (630 ears) were recruited; 75 from audiology services and 240 from schools. Full test and reference standard data were obtained for 600 ears; 155 ears were classified as truly impaired and 445 as truly hearing based on the pure tone audiometry assessment. Sensitivity was estimated to be 94.2% (95% CI 89.0% to 97.0%) for pure tone screen and 89.0% (95% CI 82.9% to 93.1%) for HearCheck (difference=5.2% favouring pure tone screen; 95% CI 0.2% to 10.1%; p=0.02). Estimates for specificity were 82.2% (95% CI 77.7% to 86.0%) for pure tone screen and 86.5% (95% CI 82.5% to 89.8%) for HearCheck (difference=4.3% favouring HearCheck; 95% CI0.4% to 8.2%; p=0.02). Conclusion Pure tone screen was better than HearCheck with respect to sensitivity but inferior with respect to specificity. As avoiding missed cases is arguably of greater importance for school entry screening, pure tone screen is probably preferable in this context.National Institute for Health Research (NIHR)University of ExeterNottingham University Hospitals National Health Service (NHS) TrustCCS NHS TrustAddenbrookes Hospital, Cambridge University Hospitals Foundation TrustUniversity of Nottingha

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

PAin SoluTions In the Emergency Setting (PASTIES)--patient controlled analgesia versus routine care in emergency department patients with non-traumatic abdominal pain: randomised trial

© Smith et al 2015. OBJECTIVE: To determine whether patient controlled analgesia (PCA) is better than routine care in providing effective analgesia for patients presenting to emergency departments with moderate to severe non-traumatic abdominal pain.DESIGN: Pragmatic, multicentre, parallel group, randomised controlled trialSETTING: Five English hospitals.PARTICIPANTS: 200 adults (66% (n=130) female), aged 18 to 75 years, who presented to the emergency department requiring intravenous opioid analgesia for the treatment of moderate to severe non-traumatic abdominal pain and were expected to be admitted to hospital for at least 12 hours.INTERVENTIONS: Patient controlled analgesia or nurse titrated analgesia (treatment as usual).MAIN OUTCOME MEASURES: The primary outcome was total pain experienced over the 12 hour study period, derived by standardised area under the curve (scaled from 0 to 100) of each participant's hourly pain scores, captured using a visual analogue scale. Pre-specified secondary outcomes included total morphine use, percentage of study period in moderate or severe pain, percentage of study period asleep, length of hospital stay, and satisfaction with pain management.RESULTS: 196 participants were included in the primary analyses (99 allocated to PCA and 97 to treatment as usual). Mean total pain experienced was 35.3 (SD 25.8) in the PCA group compared with 47.3 (24.7) in the treatment as usual group. The adjusted between group difference was 6.3 (95% confidence interval 0.7 to 11.9). Participants in the PCA group received significantly more morphine (mean 36.1 (SD 22.4) v 23.6 (13.1) mg; mean difference 12.3 (95% confidence interval 7.2 to 17.4) mg), spent less of the study period in moderate or severe pain (32.6% v 46.9%; mean difference 14.5% (5.6% to 23.5%)), and were more likely to be perfectly or very satisfied with the management of their pain (83% (73/88) v 66% (57/87); adjusted odds ratio 2.56 (1.25 to 5.23)) in comparison with participants in the treatment as usual group.CONCLUSIONS: Significant reductions in pain can be achieved by PCA compared with treatment as usual in patients presenting to the emergency department with non-traumatic abdominal pain. Trial registration European Clinical Trials Database EudraCT2011-000194-31; Current Controlled Trials ISRCTN25343280

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

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

This is the final version. Available on open access from the American Medical Association via the DOI in this recordData Sharing Statement Stevens. Evaluation of Simvastatin as a Neuroprotective Treatment for Patients With Parkinson Disease. JAMA Neurol. Published October 31, 2022. doi:10.1001/jamaneurol.2022.3718 Data Data available: Yes Data types: Deidentified participant data How to access data: By request to the data custodian/sponsor representative ([email protected] ). When available: With publication Supporting Documents Document types: None Additional Information Who can access the data: Researchers undertaking ethically approved purposes and on execution of a valid data sharing agreement. Types of analyses: Specified ethically approved purpose. Mechanisms of data availability: With a signed valid data sharing agreement.mportance 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: 16108482JP Moulton Charitable FoundationCure Parkinson’s Trus

The cost-effectiveness of patient-controlled analgesia vs. standard care in patients presenting to the emergency department in pain, who are subsequently admitted to hospital.

The clinical effectiveness of patient-controlled analgesia has been demonstrated in a variety of settings. However, patient-controlled analgesia is rarely utilised in the emergency department. The aim of this study was to compare the cost-effectiveness of patient-controlled analgesia vs. standard care in participants admitted to hospital from the emergency department with pain due to traumatic injury or non-traumatic abdominal pain. Pain scores were measured hourly for 12 h using a visual analogue scale. Cost-effectiveness was measured as the additional cost per hour in moderate to severe pain avoided by using patient-controlled analgesia rather than standard care (the incremental cost-effectiveness ratio). Sampling variation was estimated using bootstrap methods and the effects of parameter uncertainty explored in a sensitivity analysis. The cost per hour in moderate or severe pain averted was estimated as £24.77 (€29.05, US$30.80) (bootstrap estimated 95$18.86) (bootstrap estimate 95%CI £9.03 to £46.00) for participants with non-traumatic abdominal pain. Overall costs were higher with patient-controlled analgesia than standard care in both groups: pain from traumatic injuries incurred an additional £18.58 (€21.79 US$23.10) (95$25.09) (95%CI £19.45 to £20.84) per 12 h