Resolving the masers in M82

Despite first being detected in the 1970s, surprisingly little is known about the OH main line maser population in the nearby starburst galaxy M82. Sometimes referred to as 'kilomasers', they have isotropic luminosities intermediate between Galactic masers and those found in more distant megamasers. Several observations have been carried by this group over the last ten years in an attempt to get a better handle on their nature. High velocity resolution VLA observations in 2006 showed that almost all of the maser spots, distributed across the central arcminute of the galaxy, were apparently coincident with background continuum features, and a handful displayed multiple velocity components. The majority of those with velocity structure are located on a blue-shifted arc in the pv-plane, spatially located on an arc northward of the peculiar source known as B41.95+57.5. Now, new results from high spatial and spectral resolution observations with the EVN have resolved several of these masers into multiple spatial components for the first time. The maser emission is compared with known continuum sources in the galaxy, and we conclude that at least some of the maser emission is from high-gain maser action.Comment: Six pages, one table, one figure. To appear in proceedings of the 11th EVN Symposium (Bordeaux, 9-12 October 2012

Prospective observational cohort study of factors influencing trial participation in people with motor neuron disease (FIT-participation-MND): a protocol

Introduction Motor neuron disease (MND) is a rapidly progressive and fatal neurodegenerative disorder with limited treatment options. The Motor Neuron Disease Systematic Multi-Arm Randomised Adaptive Trial (MND-SMART) is a multisite UK trial seeking to address the paucity in effective disease-modifying drugs for people with MND (pwMND). Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. Failure to recruit and/or retain participants can cause insufficiently representative samples, terminated trials or invalid conclusions. This study investigates patient-specific factors affecting recruitment and retention of pwMND to MND-SMART. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention.Methods and analysis PwMND on the Scottish MND Register, Clinical Audit Research and Evaluation of MND (CARE-MND), will be invited to participate in a prospective observational cohort study that investigates factors affecting trial participation and attrition. We hypothesise that patient-specific factors will significantly affect trial recruitment and retention. Participants will complete the Hospital Anxiety and Depression Scale, 9-Item Patient Health Questionnaire and State-Trait Anxiety Inventory-Form Y to evaluate neuropsychiatric symptoms, the ALS-Specific Quality of Life Questionnaire-Brief Form and Centre for Disease Control and Prevention-Health-Related Quality of Life for quality of life and a novel study-specific questionnaire on Attitudes towards Clinical Trial Participation (ACT-Q). Clinical data on phenotype, cognition (Edinburgh Cognitive and Behavioural ALS Screen) and physical functioning (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) will also be collated. Caregivers will complete the Brief Dimensional Apathy Scale. After 12 months, a data request to MND-SMART will evaluate recruitment and retention. Descriptive statistics will summarise and compare assessments and participants reaching impairment thresholds. Variable groupings: attitudes, quality of life, cognition, behaviour, physical functioning, neuropsychiatric and phenotype. Univariate and multivariable logistic regression will explore association with participation/withdrawal in MND-SMART; presented as ORs and 95% CIs.Ethics and dissemination Ethical approval was provided by the West of Scotland Research Ethics Committee 3 (20/WS/0067) on 12 May 2020. The results of this study will be published in a peer-reviewed journal, presented at academic conferences and disseminated to participants and the public

A systematic review of non-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with common and impactful non-motor symptoms, such as neuropsychiatric symtpoms, cognitive and behavioural changes, pain, disordered sleep, fatigue and problematic saliva. AIM/HYPOTHESIS: We aimed to systematically review 25 years of ALS clinical trials data to identify if non-motor features were evaluated, in addition to the traditional measures of motor functioning and survival, and where evaluated to describe the instruments used to assess. We hypothesised that assessment of non-motor symptoms has been largely neglected in trial design and not evaluated with ALS-suitable instruments. METHODS: We reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole in 1994. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. RESULTS: 237 clinical trials, including over 29,222 participants, were investigated for their use of non-motor outcome measures. These trials evaluated neuropsychiatric symptoms (75, 32%), cognitive impairment (16, 6.8%), behavioural change (34, 14%), pain (55, 23%), sleep disturbances (12, 5%) and fatigue (18, 8%). Problematic saliva was assessed as part of composite ALS-FRS(R) scores in 184 trials (78%) but with no focus on this as an isolated symptom. 31 (13%) trials including 3585 participants did not include any assessment of non-motor symptoms. CONCLUSIONS: Non-motor symptoms such as neuropsychiatric, cognitive and behavioural changes, pain, disordered sleep, fatigue, and problematic saliva have not been consistently evaluated in trials for people with ALS. Where evaluated, non-symptoms were primarily assessed using instruments and impairment thresholds that are not adapted for people with ALS. Future trials should include non-motor symptom assessments to evaluate the additional potential therapeutic benefit of candidate drugs. PROPSERO REGISTRATION: CRD42020223648. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10651-1

Viable pathogen aerosols produced during laser dermatology surgery - a quantified analysis

The use of laser processes for surgical, medical and cosmetic procedures has been increasing with five hundred thousand workers exposed to laser surgical smoke per year. The use of lasers introduces direct beam hazards into the environment but also generates unique hazards such as material ejected from the laser process. Within this material can be potentially harmful particulate when inhaled by humans, accompanying this particulate is a foul unwanted odour. Along with the generation of these particles it is extremely possible for viable biological organisms to be generated with the particulate. Airborne particulate matter or bio-aerosols are not just a hazard to the patient, but also to other people in the environment around the laser process. The aim of this paper is to investigate and quantify the aerosol danger to both patients and operators when utilising lasers within surgical procedures, while suggesting a suitable initial solution. The tailored research for this aim will focus on whether a suitable extraction system can be developed and the effects that different types of lasers have on the size and visuals of any particulate generated. To determine whether there is a risk of infection and to ascertain the level of infection control, the possibility of viable bio-aerosols being detected after a laser process should be considered. The experiments are split into 3 sections; section 1 is the testing of the extraction system using a smoke generation system to ascertain visual proof of a functioning extraction system, section 2 is the testing of the effect of laser irradiance on the tissue simulant to determine the effect of varying laser types on the particulate generated and section 3 is the generation and measurement of bio-aerosols with the use of bio markers to test for survival of laser processing and transmission

Non-motor symptoms in motor neuron disease:Prevalence, assessment and impact

People with motor neuron disease often experience non-motor symptoms that may occur secondary to, or distinct from, motor degeneration and that may significantly reduce quality of life, despite being under-recognized and evaluated in clinical practice. Non-motor symptoms explored in this population-based study include pain, fatigue, gastrointestinal issues, poor sleep, low mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction. People registered on the Clinical Audit Research and Evaluation of motor neuron disease platform, the Scottish Motor Neuron Disease Register, were invited to complete a questionnaire on non-motor symptoms and a self-reported Amyotrophic Lateral Sclerosis Functional Rating Scale. The questionnaire comprised a pre-defined list of 11 potential non-motor symptoms, with the opportunity to list additional symptoms. A total of 120 individuals participated in this cross-sectional study, a 39% response rate of those sent questionnaires (n = 311); 99% of participants recruited (n = 120) experienced at least one non-motor symptom, with 72% (n = 120) reporting five or more. The symptoms most often reported were pain and fatigue (reported by 76% of participants, respectively). The symptoms reported to be most impactful were gastrointestinal issues (reported as ‘severe’ by 54% of participants who experienced them), followed by pain and problematic saliva (51%, respectively). Lower Amyotrophic Lateral Sclerosis Functional Rating Scale scores, indicating more advanced disease and being a long survivor [diagnosed over 8 years ago; Black et al. (Genetic epidemiology of motor neuron disease-associated variants in the Scottish population. Neurobiol Aging. 2017;51:178.e11-178.e20.)], were significantly associated with reporting more symptoms; 73% of respondents were satisfied with the frequency that non-motor symptoms were discussed in clinical care; 80% of participants indicated they believe evaluation of non-motor symptom is important to include as outcomes in trials, independent of their personal experience of these symptoms. The preferred method of assessment was completing questionnaires, at home. The overwhelming majority of people with motor neuron disease report non-motor symptoms and these frequently co-occur. Pain, fatigue, gastrointestinal issues, sleep, mood, anxiety, problematic saliva, apathy, emotional lability, cognitive complaints and sexual dysfunction are prevalent. People with motor neuron disease who had worse physical function and those who were long survivors were more likely to report more symptoms. Where reported, these symptoms are frequent, impactful and a priority for people with motor neuron disease in clinical care and trial design

The design of medical laser surgery dermatology handpieces for radiation control and direct extraction of infectious laser generated plume

Surgical skin treatments such as; laser ablation, laser scalpels, hair removal, tattooed removal etc can all generate direct and secondary optical radiation hazards, however, because they are designed to intentionally destroy human tissue, they also generate gaseous and particulate emissions. This second family often referred to as; surgical smoke, surgical smoke plume and surgical fume, have now been identified as producing viable bio-active aerosols, these by-products now pose infectious hazards to the patient and staff of the operating room. Local extraction is sometimes used to try and reduce the airborne concentration of these byproducts though in virtually all cases the smell of the process is detectable by all. The optical radiation hazard usually dictates the wearing of protective eyewear to provide some level of personal protection. A major health concern to all medical and cosmetic facilities is that of infection control. Surgical smoke is usually overlooked as a source of infection within the operating environment and it has been known since the mid-1980s that the particulate can carry with it live pathogens from the patient which can now be in skin contact or respired by the operating staff. A paper presented by the authors in the Medical Session here at ILSC provides possibly the first quantitative analysis of the hazards the surgeon and other staff are subject to. This paper examines the practical limitations of the existing approaches and provides some simple practical control measures that provide complete radiation containment as well as enable complete particulate and gas extraction without any reliance on any form of personal protection for the patient and operating staff. These designs have now been tested and are shown to offer 100% effective plume extraction and radiation containment

A systematic review of neuropsychiatric and cognitive assessments used in clinical trials for amyotrophic lateral sclerosis

Background: Up to 50% of people with amyotrophic lateral sclerosis (ALS) experience cognitive dysfunction, whilst depression and anxiety are reported in up to 44% and 33%, respectively. These symptoms impact on quality of life, and are associated with a poorer prognosis. Historically, outcomes in clinical trials have focused on the effect of candidate drugs on physical functioning.Methods: We reviewed the past 25 years of clinical trials of investigative medicinal products in people with ALS, since the licensing of riluzole, and extracted data on frequency and type of assessment for neuropsychiatric symptoms and cognitive impairment. Trial registry databases, including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed, were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 31/10/2019. No language restrictions were applied. Outcome measures, exclusion criteria and assessment tool used were extracted.Results: 216 trials, investigating 26,326 people with ALS, were reviewed. 35% assessed neuropsychiatric symptoms, and 22% assessed cognition, as Exclusion Criteria or Outcome Measures. 3% (n = 6) of trials assessed neuropsychiatric symptoms as a Secondary Outcome Measure, and 4% (n = 8) assessed cognition as Outcome Measures; only one trial included assessments for both cognition and neuropsychiatric symptoms as Outcome Measures. Three ALS-specific assessments were used in six trials.Conclusions: Trials for people with ALS have neglected the importance of neuropsychiatric symptoms and cognitive impairment. Evaluation of these extra-motor features is essential to understanding the impact of candidate drugs on all symptoms of ALS.</p

A systematic review of digital technology to evaluate motor function and disease progression in motor neuron disease

Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional Rating Scale—Revised (ALS-FRS(R)), a clinician-administered questionnaire providing a composite score on physical functioning. Technology offers a potential alternative for assessing motor progression in both a clinical and research capacity that is more sensitive to detecting smaller changes in function. We reviewed studies evaluating the utility and suitability of these devices to evaluate motor function and disease progression in people with MND (pwMND). We systematically searched Google Scholar, PubMed and EMBASE applying no language or date restrictions. We extracted information on devices used and additional assessments undertaken. Twenty studies, involving 1275 (median 28 and ranging 6–584) pwMND, were included. Sensor type included accelerometers (n = 9), activity monitors (n = 4), smartphone apps (n = 4), gait (n = 3), kinetic sensors (n = 3), electrical impedance myography (n = 1) and dynamometers (n = 2). Seventeen (85%) of studies used the ALS-FRS(R) to evaluate concurrent validity. Participant feedback on device utility was generally positive, where evaluated in 25% of studies. All studies showed initial feasibility, warranting larger longitudinal studies to compare device sensitivity and validity beyond ALS-FRS(R). Risk of bias in the included studies was high, with a large amount of information to determine study quality unclear. Measurement of motor pathology and progression using technology is an emerging, and promising, area of MND research. Further well-powered longitudinal validation studies are needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11312-7