Implementation of a drive cylinder for low collisional experiments on magnetic reconnection.

For most laboratory plasma experiments, Coulomb collisions between the particle species are sufficiently frequent that the particle distribution functions are relaxed to a near-Maxwellian form. This hampers the applicability of such experiments to phenomena observed in tenuous and near-collisionless space plasma. The Terrestrial Reconnection EXperiment (TREX) at the Wisconsin Plasma Physics Laboratory aims to study collisionless reconnection for parameters relevant to the Earth's magnetosphere. To reduce the role of collisional effects, a reconnection Drive Cylinder has been developed, which increases both the effective system size of the TREX configuration and the rate at which reconnection can be driven. These two effects now permit TREX to reach a kinetic reconnection regime where collisional effects are minimized. The Drive Cylinder is comprised of 12 single loop drive-coils connected in parallel to a 10 kV capacitor bank. Insulated sheets of aluminum are applied to smooth the magnetic fields and enhance the drive efficiency. Following is a description of the technical details and performance of the Drive Cylinder.

A Geospatial Analysis of Social and Structural Determinants of Health and High HIV Prevalence in Alabama, USA.

OBJECTIVE: This study utilizes geospatial analytic techniques to examine HIV hotspots in Alabama leveraging Medicaid utilization data. METHODS: This cross-sectional study leveraged Medicaid utilization data from Alabama's 67 counties, averaging 9,861 Medicaid recipients aged > 18 years old per county. We used Alabama Medicaid administrative claims data from January 1, 2016, to December 31, 2020, to identify individuals with HIV. Using Microsoft SQL Server, we obtained the average annual count of HIV Medicaid claims in each of the 67 Alabama counties (numerator) and the number of adult Medicaid recipients in each county (denominator), and standardized with a multiplier of 100,000. We also examined several other area-level summary variables (e.g., non-high school completion, income greater than four times the federal poverty level, social associations, urbanicity/rurality) as social and structural determinants of health. County-boundary choropleth maps were created representing the geographic distribution of HIV rates per 100,000 adult Medicaid recipients in Alabama. Leveraging ESRI ArcGIS and local indicators of spatial association (LISA), results were examined using local Moran's I to identify geographic hotspots. RESULTS: Eleven counties had HIV rates higher than 100 per 100,000. Three were hotspots. Being an HIV hotspot was significantly associated with relatively low educational attainment and less severe poverty than other areas in the state. CONCLUSIONS: Findings suggesting that the HIV clusters in Alabama were categorized by significantly less severe poverty and lower educational attainment can aid ongoing efforts to strategically target resources and end the HIV epidemic in U.S.' Deep South.

Examining the Effect of Income-Based Inequalities and Dental Service Provision on Dental Service Utilization among Older Australians: A Multiple Mediation Analysis.

INTRODUCTION: Public service provision is one of the keys to reducing inequalities in the utilization of dental services. Given the increase in the aging population, there should be a focus on older adults' oral health. However, this is often overlooked. OBJECTIVES: This study investigates the effectiveness of public services in reducing income-related inequalities in dental service utilization among older South Australians. METHODS: A multiple counterfactual mediation analysis using the ratio of mediator probability weighting approach was used to explore the proposed mediation mechanism using a South Australian population of older adults (≥65 y). The exposure variable in the analysis was income, and the mediators were concession cards and the last dental sector (public or private). The outcome variable was the time of last dental visit. RESULTS: Half of the older adults with high income (≥$40,000) owned a concession card, and 10% of those who attended public dental services belonged to this group. Interestingly, only 16.3% of the study participants had visited the public dental sector at their last dental appointment. Results showed a negligible indirect effect (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.85-1.05) and a significant direct effect (OR, 3.09; 95% CI, 2.24-4.87). By changing the potential outcome distributions to the counterfactual exposure distributions and taking the mediators' distribution as a counterfactual exposure distribution, the odds of dental visits occurring before the past 12 mo approximately tripled for low-income compared to high-income individuals. CONCLUSION: Income inequalities were associated with relatively delayed dental visits in older South Australians, and provision of public services could not improve this pattern. This might happen due to inequitable access to concession cards and public services. A review of policies is required, including addressing income inequalities and implementing short-term approaches to improve service utilization patterns in older South Australians. KNOWLEDGE TRANSFER STATEMENT: The findings of this study can enable policymakers for informed decision-making about the provision of public dental services for older Australians. This study emphasizes the importance of reviewing the current public dental services and subsidies and implementing short-term approaches to reduce income inequalities for older Australians.

Oral health messages for Australia: A national consensus statement.

BACKGROUND: Oral health promotion initiatives must be evidence-based and consistent with broader health messaging. The Oral Health Messages for the Australian Public were first produced in 2009 and sought to enable a focused, and strategic approach to oral health promotion in Australia. As the evidence base and needs of the Australian population have since changed, this consensus statement was updated in 2022-2023. METHODS: The process of updating the messages consisted of 3 phases (preparatory phase, the Delphi technique, final revision phase). The preparatory phase included public and expert consultation, an umbrella review of published scientific literature and review of available recommendations, policies and guidelines. The Delphi technique used in this study was guided by Guidance on Conducting and REporting DElphi Studies (CREDES) and included 2 voting rounds. There were 70 experts in round 1 and 60 experts in round 2. Delphi participants comprised of experts from a variety of fields to ensure diversity and inclusion, balance expertise and maximize stakeholder representation. Consensus was defined as 75% agreement. RESULTS: A total of 11 messages were included in the 2022 update of Oral Health Messages for Australia. CONCLUSION: The updated oral health messages will support oral health promotion policy and activity at both individual and population level to improve the oral health of Australians.

Racial identity and concussion diagnosis and recovery trajectories in collegiate athletes: a LIMBIC MATARS investigation.

OBJECTIVE: To determine if there were concussion diagnosis and recovery disparities between collegiate athletes with Black and White racial identities. DESIGN: Retrospective cohort study. METHODS: Concussion information was extracted from NCAA athlete medical files at LIMBIC MATARS member institutions from the 2015-16' to 2019-20' academic years. A total of 410 concussions from 9 institutions were included that provided all independent (i.e. racial identity of Black or White) and dependent variable information (i.e. dates of injury, diagnosis, symptom resolution, and return to sport) that were analyzed using Mann-Whitney U tests. The sample consisted of 114 (27.8%) concussions sustained by Black athletes and 296 (72.1%) sustained by White athletes. RESULTS: The overall sample had a median of 0 days between injury occurrence to diagnosis, 7 days to symptom resolution, and 12 days to return to sport. No significant timing differences were observed for concussion diagnosis (p = .14), symptom resolution (p = .39), or return to sport (p = 0.58) between collegiate athletes with Black versus White racial identities. CONCLUSIONS: These findings may reflect equitable access to onsite sports medicine healthcare resources that facilitate concussion management in the collegiate sport setting. Future work should explore these associations with a larger and more diverse sample of collegiate athletes.

Differential diagnosis of suspected multiple sclerosis: an updated consensus approach.

Accurate diagnosis of multiple sclerosis requires careful attention to its differential diagnosis-many disorders can mimic the clinical manifestations and paraclinical findings of this disease. A collaborative effort, organised by The International Advisory Committee on Clinical Trials in Multiple Sclerosis in 2008, provided diagnostic approaches to multiple sclerosis and identified clinical and paraclinical findings (so-called red flags) suggestive of alternative diagnoses. Since then, knowledge of disorders in the differential diagnosis of multiple sclerosis has expanded substantially. For example, CNS inflammatory disorders that present with syndromes overlapping with multiple sclerosis can increasingly be distinguished from multiple sclerosis with the aid of specific clinical, MRI, and laboratory findings; studies of people misdiagnosed with multiple sclerosis have also provided insights into clinical presentations for which extra caution is warranted. Considering these data, an update to the recommended diagnostic approaches to common clinical presentations and key clinical and paraclinical red flags is warranted to inform the contemporary clinical evaluation of patients with suspected multiple sclerosis.

Design and testing the validity of an inexpensive and accessible sham dry needling protocol.

OBJECTIVE: To use a simple method of needle blunting to produce a placebo dry needling protocol which is indistinguishable from the sensations felt during therapeutic dry needling. METHODS: A randomised cross-over design was used to compare the perception of needle skin penetration, pain experienced and types of sensations experienced following a single placebo dry needling and a single therapeutic dry needling application. RESULTS: There were no significant differences in the proportions of patients reported ability to perceive needle penetration (p = 0.646), description of needling sensations (p = 0.3) or pain rating (p = 0.405) when comparing placebo needling to therapeutic dry needling. CONCLUSION: Needle tip bending creates a simple, cost-effective and effective placebo needle for use in comparisons with therapeutic dry needling. This offers researchers a viable alternative to expensive and inappropriate acupuncture sham devices when conducting dry needling trials.

Comparative effectiveness of cladribine tablets versus fingolimod in the treatment of highly active multiple sclerosis: A real-world study.

BACKGROUND: Cladribine tablets and fingolimod have similar marketing authorisations in Europe for the treatment of patients with highly active relapsing multiple sclerosis (HA-RMS). In the absence of direct head-to-head studies, real-world data are important to assess the comparative effectiveness of these oral disease-modifying therapies (DMTs). The primary objective of the present study was to compare relapse rates between patients who received either cladribine tablets or fingolimod. METHODS: This multicentre retrospective study conducted in the United Kingdom and Germany assessed non-inferiority in relapse rates of cladribine tablets versus fingolimod in HA-RMS patients over a 12-month period. Eligible patients who initiated treatment with cladribine tablets or fingolimod at least 12 months prior to the screening date were sampled consecutively until the target sample size was reached. Patients were censored at discontinuation of study treatment, commencement of another DMT, death, loss to follow-up, or at 12 months post-baseline, whichever happened earliest. The primary analytic timeframe for physician-confirmed relapse outcomes was the study effectiveness period (nine months of follow-up after an initial 12 weeks of treatment). Propensity score analysis was applied based on the inverse probability of treatment weighting approach. RESULTS: The primary analytic cohort consisted of 1,095 HA-RMS patients: 610 (55.7%) receiving cladribine tablets and 485 (44.3%) receiving fingolimod. Fewer patients discontinued cladribine tablets and/or switched to another DMT compared with fingolimod (0.2% versus 3.5%, respectively). The primary endpoint, adjusted annualised relapse rate (ARR), was 0.10 (95% confidence interval [CI]: 0.07-0.14) for cladribine tablets and 0.14 (95% CI: 0.10-0.20) for fingolimod. The adjusted ARR ratio of cladribine tablets versus fingolimod was 0.68 (95% CI: 0.42-1.11). Given the entire 95% CI was less than the non-inferiority margin of 1.2, cladribine tablets was non-inferior to fingolimod. CONCLUSIONS: In this real-world retrospective cohort study, cladribine tablets demonstrated comparable effectiveness to fingolimod at one year following treatment initiation. The full treatment dosage of cladribine tablets is completed over two years and so these results may be conservative.

Understanding the Experiences of Food Insecurity in Older Adult Households.

Food insecurity is a pressing multidimensional problem that negatively impacts the health and well-being of a significant number of the older population. Finding ways to better address nutritional issues among this vulnerable population is vital to their well-being. Using a mixed-methods approach, we conducted semi-structured phone interviews with a representative sample of 434 low-income older adult households in Tennessee. The aim of this study is to assess the prevalence of food insecurity, examine ongoing barriers, and, using qualitative data, to explore the diverse daily experiences older adults face when confronted with a food insecure lifestyle. Based on the USDA Adult 10-Item Household Screening Module, we found that 30% in our sample were designated as marginally, low or very low food secure. Many of those most vulnerable (older women, widowed or divorced, poor health and below the poverty line) constantly struggled with food insecurity. Being food insecure was attributed to limited financial resources, lack of transportation, health limitations, and a poor psychological state. Utilizing food stretching practicing, governmental agencies offering food supplements, family/friends, religious groups and personal resilience were common coping strategies. Implications and recommendations for service providers are offered.

Breed distribution of spontaneous chronic corneal epithelial defects in UK dogs.

BACKGROUND: This study aimed to assess the risk of bilateral disease in dogs affected by spontaneous chronic corneal epithelial defects (SCCEDs) and identify any recent changes in the distribution of breeds affected. METHODS: Medical records of dogs assessed at a single ophthalmic centre for the management of SCCEDs between 2007 and 2020 were reviewed, and clinical data were extracted. RESULTS: Three hundred and seven dogs met the inclusion criteria. Boxers (129 dogs), Staffordshire Bull Terriers (37 dogs) and French Bulldogs (20 dogs) were most frequently affected. Overall, the median age at presentation was 8 years (range 1-15 years), but French Bulldogs had a younger median age of 6 years. Boxers, French Bulldogs and Staffordshire Bull Terriers showed higher odds of bilateral ulceration (odds ratio 1.79, 1.65 and 1.64, respectively) compared to the overall study population. The median time between presentations when both eyes were affected was 4 months (range 0-42 months). There was a statistically significant increase in French Bulldogs, a reduction in Boxers and a stable number of Staffordshire Bull Terriers treated for this condition. However, as the effective sample size from each individual breed was small, further studies would be beneficial to confirm these findings. CONCLUSION: The results from this study suggest a shift in breed distribution. The risk of bilateral disease is higher in the three breeds reported here, and owners should be counselled appropriately at the initial examination.

HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis.

BACKGROUND: Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved. OBJECTIVE: To determine the influence of HLA-DRB1*1501 on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients. METHODS: One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years. HLA-DRB1*1501 status was determined using Sanger sequencing and tagging of the rs3135388 polymorphism. Linear/Poisson mixed-effects models were used to investigate rates of change in EDSS and MRI measures based on HLA-DRB1*1501 status. RESULTS: HLA-DRB1*1501 -positive (n = 52) patients showed a faster rate of disability worsening compared with the HLA-DRB1*1501 -negative (n = 55) patients (annualised change in EDSS 0.14/year vs. 0.08/year, p < 0.025), and a greater annualised change in T2 lesion volume (adjusted difference 0.45 mL/year, p < 0.025), a higher number of gadolinium-enhancing lesions, and a faster rate of brain (adjusted difference -0.12%/year, p < 0.05) and spinal cord atrophy (adjusted difference -0.22 mm2/year, p < 0.05). INTERPRETATION: These findings provide evidence that the HLA-DRB1*1501 allele plays a role in MS severity, as measured by long-term disability worsening and a greater extent of inflammatory disease activity and tissue loss. HLA-DRB1*1501 may provide useful information when considering prognosis and treatment decisions in early relapse-onset MS.

Internet Use as a Moderator of the Relationship between Age and Depression: Implications for Older Adults.

Technology-based interventions have been suggested to prevent depression and loneliness. However, it is not yet well-established if internet use is a protective factor for older adults, allowing them to combat depression and loneliness. Addressing this neglected area of research, this paper examines whether frequent internet use moderated the relationship between depression and age. Using 2016 General Social Survey (n = 869), a series of ordinary least squares regression models were employed. The findings revealed that older adults who frequently used the internet were more depressed than those who did not. This may imply that internet use by older individuals may not be an adequate source of social engagement and may even heighten existing levels of depression. Other interventions may need to be developed to compensate for the loss of physical contact and reduce the level of depression.

Use of follow-on disease-modifying treatments for multiple sclerosis: Consensus recommendations.

BACKGROUND: As patents for multiple sclerosis (MS) therapies expire, follow-on disease-modifying treatments (FO-DMTs) become available at reduced cost. Concerns exist that cheaper FO-DMTs are used simply to reduce healthcare costs. However, the well-being of people with MS should take priority. OBJECTIVES: To identify best practices for FO-DMT development and use by agreeing on principles and consensus statements through appraisal of published evidence. METHODS: Following a systematic review, we formulated five overarching principles and 13 consensus statements. Principles and statements were voted on by a multidisciplinary panel from 17 European countries, Argentina, Canada and the United States. RESULTS: All principles and statements were endorsed by >80% of panellists. In brief, FO-DMTs approved within highly regulated areas can be considered effective and safe as their reference products; FO-DMTs can be evaluated case by case and do not always require Phase III trials; long-term pharmacovigilance and transparency are needed; there is lack of evidence for multiple- and cross-switching among FO-DMTs; and education is needed to address remaining concerns. CONCLUSION: Published data support the use of FO-DMTs in MS. The consensus may aid shared decision-making. While our consensus focused on Europe, the results may contribute to enhanced quality standards for FO-DMTs use elsewhere.

The prognostic significance of early blood neurofilament light chain concentration and magnetic resonance imaging variables in relapse-onset multiple sclerosis.

BACKGROUND: Improved prognostication remains vital in multiple sclerosis to inform personalized treatment approaches. Blood neurofilament light (bNfL) is a promising prognostic biomarker, but to what extent it provides additional information, independent of established MRI metrics, is yet to be established. METHODS: We obtained all available bNfL data for 133 patients from a longitudinal observational cohort study. Patients were dichotomized into good or poor outcome groups based upon clinical and cognitive assessments performed 15 years after a clinically isolated syndrome. We performed longitudinal modeling of early NfL and MRI variables to examine differences between outcome groups. RESULTS: The bNfL dataset was incomplete, with one to three (mean 1.5) samples available per participant. Within 3 months of onset, bNfL was similar between groups. The bNfL concentration subsequently decreased in those with a good outcome, and remained persistently elevated in those with a poor outcome. By year 5, NfL in the poor outcome group was approximately double that of those with a good outcome (14.58 [10.40-18.77] vs. 7.71 [6.39-9.04] pg/ml, respectively). Differences were reduced after adjustment for longitudinal changes in T2LV, but trends persisted for a greater rate of increase in NfL in those with a poor outcome, independent of T2LV. CONCLUSIONS: This analysis requires replication in cohorts with more complete bNfL datasets, but suggests that persistently elevated blood NfL may be more common in patients with a poor long-term outcome. Persistent elevation of blood NfL may provide additional prognostic information not wholly accounted for by standard monitoring techniques.

Evaluating Enzymatic Productivity-The Missing Link to Enzyme Utility.

Kinetic productivity analysis is critical to the characterization of enzyme catalytic performance and capacity. However, productivity analysis has been largely overlooked in the published literature. Less than 0.01% of studies which report on enzyme characterization present productivity analysis, despite the fact that this is the only measurement method that provides a reliable indicator of potential commercial utility. Here, we argue that reporting productivity data involving native, modified, and immobilized enzymes under different reaction conditions will be of immense value in optimizing enzymatic processes, with a view to accelerating biotechnological applications. With the use of examples from wide-ranging studies, we demonstrate that productivity is a measure of critical importance to the translational and commercial use of enzymes and processes that employ them. We conclude the review by suggesting steps to maximize the productivity of enzyme catalyzed reactions.

Prophylactic efficacy of intravenous paracetamol administration to reduce the incidence of post-operative ocular hypertension in dogs undergoing phacoemulsification: A pilot study.

PURPOSE: To determine whether intravenous administration of paracetamol can prevent postoperative ocular hypertension (POH) in dogs following routine phacoemulsification. METHODS: Diabetic and non-diabetic patients (total 54 dogs) undergoing unilateral or bilateral phacoemulsification were recruited to this placebo-controlled, prospective study. The control group received 1 ml/kg saline via intravenous infusion while the treatment group received 10 mg/kg paracetamol via intravenous infusion. Infusions were administered 30 min prior to surgery and repeated 12 h following initial administration. All patients received topical latanoprost at the conclusion of surgery. Intraocular pressure (IOP) was measured before premedication (baseline), and at 1 h, 3 h, 5 h and 18 h following extubation. POH was defined as an IOP above 25 mmHg (POH25). In addition, the number of patients with an IOP exceeding 20 mmHg was analyzed (POH20). RESULTS: POH20 occurred in 33 of 54 animals (61.1%), including 19 of 25 animals (76.0%) in the control group and 14 of 29 animals (55.2%) in the treatment group. POH25 occurred in 23 of 44 animals (52.3%), including 13 of 25 animals (52.0%) in the control group and 10 of 29 animals (34.5%) in the treatment group. Paracetamol administration showed a significant positive effect on reducing the incidence of POH20 (p = .048), but not POH25 (p = .221). CONCLUSIONS: When comparing groups, treatment with paracetamol showed a statistically significant reduction in the incidence of POH20, although no differences were observed in the incidence of POH25 between groups. Further studies are warranted to explore whether alternative drug regimes or routes of administration can provide enhanced efficacy in the prevention of POH25.

Pausing transplants in the face of a global pandemic: Patient survival implications.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted normal operating procedures at transplant centers. With the possibility that COVID-19 infection carries an overall 4% mortality rate and potentially a 24% mortality rate among the immunocompromised transplant recipients, many transplant centers considered the possibility of slowing down and even potentially pausing all transplants. Many proposals regarding the need for pausing organ transplants exist; however, much remains unknown. Whereas the impact of the COVID-19 pandemic on the overall healthcare system is unknown, the potential impact of pausing organ transplants over a period can be estimated. This study presents a model for evaluating the impact of pausing liver transplants over a spectrum of model for end-stage liver disease-sodium (MELD-Na) scores. Our model accounts for two potential risks of a pause: (1) the waitlist mortality of all patients who do not receive liver transplants during the pause period, and (2) the impact of a longer waiting list due to the pause of liver transplants and the continuous accrual of new patients. Using over 12 years of liver transplant data from the United Network for Organ Sharing and a system of differential equations, we estimate the threshold probability above which a decision maker should pause liver transplants to reduce the loss of patient life months. We also compare different pause policies to illustrate the value of patient-specific and center-specific approaches. Finally, we analyze how capacity constraints affect the loss of patient life months and the length of the waiting list. The results of this study are useful to decision makers in deciding whether and how to pause organ transplants during a pandemic. The results are also useful to patients (and their care providers) who are waiting for organ transplants.

Characterisation of Bacteriophage vB_SmaM_Ps15 Infective to Stenotrophomonas maltophilia Clinical Ocular Isolates.

Recent acknowledgment that multidrug resistant Stenotrophomonas maltophilia strains can cause severe infections has led to increasing global interest in addressing its pathogenicity. While being primarily associated with hospital-acquired respiratory tract infections, this bacterial species is also relevant to ophthalmology, particularly to contact lens-related diseases. In the current study, the capacity of Stenotrophomonas phage vB_SmaM_Ps15 to infect ocular S. maltophilia strains was investigated to explore its future potential as a phage therapeutic. The phage proved to be lytic to a range of clinical isolates collected in Australia from eye swabs, contact lenses and contact lens cases that had previously shown to be resistant to several antibiotics and multipurpose contact lenses disinfectant solutions. Morphological analysis by transmission electron microscopy placed the phage into the Myoviridae family. Its genome size was 161,350 bp with a G + C content of 54.2%, containing 276 putative protein-encoding genes and 24 tRNAs. A detailed comparative genomic analysis positioned vB_SmaM_Ps15 as a new species of the Menderavirus genus, which currently contains six very similar globally distributed members. It was confirmed as a virulent phage, free of known lysogenic and pathogenicity determinants, which supports its potential use for the treatment of S. maltophilia eye infections.