On Identifying and Mitigating Bias in Inferred Measurements for Solar Vector Magnetic-Field Data.

The problem of bias, meaning over- or under-estimation, of the component perpendicular to the line-of-sight [ B ⊥ ] in vector magnetic-field maps is discussed. Previous works on this topic have illustrated that the problem exists; here we perform novel investigations to quantify the bias, fully understand its source(s), and provide mitigation strategies. First, we develop quantitative metrics to measure the B ⊥ bias and quantify the effect in both local (physical) and native image-plane components. Second, we test and evaluate different options available to inversions and different data sources, to systematically characterize the impacts of these choices, including explicitly accounting for the magnetic fill fraction [ f f ]. Third, we deploy a simple model to test how noise and different models of the bias may manifest. From these three investigations we find that while the bias is dominantly present in under-resolved structures, it is also present in strong-field, pixel-filling structures. Noise in the spectropolarimetric data can exacerbate the problem, but it is not the primary cause of the bias. We show that fitting f f explicitly provides significant mitigation, but that other considerations such as the choice of χ 2 -weights and optimization algorithms can impact the results as well. Finally, we demonstrate a straightforward "quick fix" that can be applied post facto but prior to solving the 180 ∘ ambiguity in B ⊥ , and which may be useful when global-scale structures are, e.g., used for model boundary input. The conclusions of this work support the deployment of inversion codes that explicitly fit f f or, as with the new SyntHIA neural-net, that are trained on data that did so.

Oro-mucosal midazolam maleate: Use and effectiveness in adults with epilepsy in the UK.

BACKGROUND: Oro-mucosal midazolam maleate (OMM) with suitable training to family and carers is being increasingly recognized as the treatment of choice to mitigate the development of status epilepticus in non-hospital community settings. There are no studies to describe the use, effectiveness, and suitable dosing of OMM in adults with epilepsy in community settings. PURPOSE: To describe the use, effectiveness, and dosing of OMM in the emergency treatment of epileptic seizures in community settings. METHODS: A retrospective observational study (2016-17) design was used with participant recruitment from four UK NHS secondary care outpatient clinics providing epilepsy management. Study sample was of adult people with epilepsy (PWE) having had a recent seizure requiring OMM. Data on patient demographics, patient care plans, details of a recent seizure requiring emergency medication, and dose of OMM were collected from medical records. RESULTS: Study data from 146 PWE were included. The mean age of PWE was 41.0 years (SD 15.2) and mean weight was 64.8Kg (SD 18.2). Fifty-three percent of PWE were recorded as having intellectual disability. The most frequently used concomitant medications were lamotrigine (43%). The majority of seizures occurred at people's homes (n = 92, 63%). OMM was most often administered by family/professional care-givers (n = 75, 48.4%). Generalized (tonic/clonic) seizures were recorded in most people (n = 106, 72.6%). The most common initial dose of OMM was 10 mg (n = 124, 84.9%). The mean time to seizure cessation after administration of this initial dose was 5.5 minutes (SD = 4.5, Median 5.0, IQR 2.1-5.0). Only a minority of seizures led to ambulance callouts (n = 18, 12.3%) or hospital admissions (n = 13, 9%). CONCLUSION: This is the first observational study describing the use and effectiveness of OMM in adults in community settings. Minimal hospital admissions were reported in this cohort and the treatment was effective in ending seizures in adults in community settings.

Surveillance for COVID-19 in the English Football League 2019-2020.

Medical surveillance and risk mitigation protocols to reduce viral transmission have underpinned the return of elite football during the COVID-19 pandemic. This article describes the evidence-informed approach and surveillance findings from the English Football League across a 9-week period at the end of the 2019-20 season. Protocols were devised by the lead EFL Medical Advisor with specialist occupational medicine input. Isolation requirements for cases and contacts were in-line with UK Government regulations, with external contact tracing conducted by local public health authorities. Quantitative PCR testing was conducted twice weekly and within 72 hours of fixtures. Forty-three individuals, including 18 players returned positive tests. No positive results were returned after week 5 (round 10). Our findings support those from other leagues that with appropriate compliance, elite football can continue safely during this pandemic. We recommend that protocols and compliance should be revised as necessary according to community prevalence and changes in viral transmission dynamics.

Interassociation consensus recommendations for pitch-side emergency care and personal protective equipment for elite sport during the COVID-19 pandemic.

The COVID-19 pandemic has necessitated many novel responses in healthcare including sport and exercise medicine. The cessation of elite sport almost globally has had significant economic implications and resulted in pressure to resume sport in very controlled conditions. This includes protecting pitch-side medical staff and players from infection. The ongoing prevalence of SARS-CoV-2 and the desire to resume professional sport required urgent best practice guidelines to be developed so that sport could be resumed as safely as possible. This set of best practice recommendations assembles early evidence for managing SARS-CoV-2 and integrates expert opinion to provide a uniform and pragmatic approach to enhance on-field and pitch-side safety for the clinician and player. The nature of SARS-CoV-2 transmission creates new hazards during resuscitation and emergency care and procedures. Recommendations for the use and type of personal protective equipment during on-field or pitch-side emergency medical care is provided based on the clinical scenario and projected risk of viral transmission.

From Passive Patient to Engaged Partner: My Journey With Parkinson Disease.

This patient narrative by Richard Higgins with Maureen Hennessey describes Richard's journey of learning to live with a chronic and progressive illness. It begins with Richard's diagnosis and shares many of the lessons learned along the way. Richard copes daily with this condition, relying on the support and expertise of his wife and the treatment team he has assembled while also encouragingly drawing on the skills and knowledge gained as a longtime running coach. A clinical commentary is provided at the article's conclusion, drafted by Richard's friend, Maureen Hennessey, PhD, CPCC, CPHQ, offering observations about the relevance of Richard's story to participatory medicine and suggesting pertinent resources for patients and health care professionals.

Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury.

OBJECTIVES: To determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS). METHODS: Data were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases. RESULTS: The transcriptional program in the CNS following TBI, HS, and VPA treatment includes activation of regulatory pathways that enhance neurogenesis and suppress gliogenesis. Genes which encode the transcription factors (TFs) that specify neuronal cell fate, including MEF2D, MYT1L, NEUROD1, PAX6 and TBR1, and their target genes, are induced by VPA. VPA represses genes responsible for oligodendrogenesis, maintenance of white matter, T-cell activation, angiogenesis, and endothelial cell proliferation, adhesion and chemotaxis. NEUROD1 has regulatory interactions with 38% of the genes regulated by VPA in a swine model of TBI and HS in adult brain. Hi-C spatial mapping of a VPA pharmacogenomic SNP in the GRIN2B gene shows it is part of a transcriptional hub that contacts 12 genes that mediate chromatin-mediated neurogenesis and neuroplasticity. CONCLUSIONS: Following TBI and HS, this study shows that VPA administration acts in the adult brain through differential activation of TFs responsible for neurogenesis, genes responsible for neuroplasticity, and repression of TFs that specify oligodendrocyte cell fate, endothelial cell chemotaxis and angiogenesis. Short title: Mechanism of action of valproic acid in traumatic brain injury.

Matrix Metalloproteinase-9 Regulates Neuronal Circuit Development and Excitability.

In early postnatal development, naturally occurring cell death, dendritic outgrowth, and synaptogenesis sculpt neuronal ensembles into functional neuronal circuits. Here, we demonstrate that deletion of the extracellular proteinase matrix metalloproteinase-9 (MMP-9) affects each of these processes, resulting in maladapted neuronal circuitry. MMP-9 deletion increases the number of CA1 pyramidal neurons but decreases dendritic length and complexity. Parallel changes in neuronal morphology are observed in primary visual cortex and persist into adulthood. Individual CA1 neurons in MMP-9(-/-) mice have enhanced input resistance and a significant increase in the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs). Additionally, deletion of MMP-9 significantly increases spontaneous neuronal activity in awake MMP-9(-/-) mice and enhances response to acute challenge by the excitotoxin kainate. Our data document a novel role for MMP-9-dependent proteolysis: the regulation of several aspects of circuit maturation to constrain excitability throughout life.

Feeling like a clerk in H. G. Wells.

In three turn-of-the-century novels about clerks and scholarship boys, H. G. Wells illustrates the emotional impact of social hierarchies on individual lives. By portraying the conflicted, class-related emotions of lower-middle-class men, Wells departs from the common contemporary image of the clerk as a figure synonymous with his function. But Wells depicts other emotions--specifically, those associated with domesticity and recklessness--to push against what he sees as the classed nature of emotional lives. He rewrites Victorian domesticity as a zone of sexuality and desire for his lower-middle-class clerks, and he mobilizes an emergent cultural appreciation of recklessness to instill them with vitality. The "significant selves" that develop as a result help to offset their ultimate failure to escape their class.

Class half-empty? Pre-registration house officer attendance at weekly teaching sessions: implications for delivering the new Foundation Programme curriculum.

This study aimed to explore patterns of attendance at classroom-based, taught education programmes for pre-registration house officers (PRHOs) and to identify reasons for non-attendance, and to consider implications for Foundation Programme curriculum delivery and suggest strategies for improving delivery. We analysed registers of attendance for education sessions for 3 local teaching hospitals in the Leicestershire, Northamptonshire and Rutland (LNR) Healthcare Workforce Deanery, along with PRHO exit questionnaire returns (from 2001 to 2005). Despite a trend for attendance to fall slightly over the course of a rotation, attendance rates have, in general, remained relatively stable at around two-thirds. However, during most 4-month posts, a fifth or more of PRHOs missed half or more of all sessions. Two types of barrier to attendance were identified: 'routine barriers', which relate to hospital working patterns, and 'contextual barriers', which refer to the particularities of each hospital post. There was no evidence that doctors' motivation and commitment towards the education programme is a main determinant of attendance. Contextual barriers to attendance, such as pressure being placed on PRHOs to remain on the ward, can be addressed. However, routine barriers to attendance, including on-call working patterns and annual leave, render it impossible to avoid significant numbers of education sessions being missed by PRHOs in each post during a rotation. En bloc teaching of basic generic skills prior to the start of the rotation plus greater use of online learning resources are examples of ways in which reliance on in-post, classroom-based programmes can be reduced.

Design and demonstration of a switching engine for a binary true-time-delay device that uses a white cell.

Optical true-time-delay devices based on the White cell can be divided into two general types: polynomial cells, in which the number of delays that can be obtained is related to the number of times m that a beam bounces in the cell raised to some power, and exponential cells, in which the number of delays is proportional to some number raised to the power of m. In exponential cells, the topic to be addressed, the spatial light modulator switches between a delay element and a null path on each bounce. We describe an improved design of this switching engine, which contains a liquid-crystal switch and a White cell. We examine astigmatism and corrections for it and present a specific design.