Open-source 3-D printable autoinjector: Design, testing, and regulatory limitations.

Autoinjectors have become popular modern injectable medical devices used as drug delivery systems. Due to their ease, capability and reliability compared to other conventional injectable medical devices, the market and manufacturing demand for autoinjector devices are increasing rapidly and expected to reach a market of $37.5 billion globally by 2025. Although autoinjectors can offset healthcare treatment costs through self-administered medication, they can be expensive for consumers, which limit their accessibility. This study describes the design and manufacture of a spring-driven and 3-D printed autoinjector to overcome this economic accessibility challenge. The digitally replicable device is released as open-source hardware to enable low-cost distributed manufacturing. The bill of materials and assembly instructions are detailed, and the effectiveness of the autoinjector is tested against the current standard (ISO 11608-1:2022) for needle-based injection systems. The safety and dosing accuracy was tested by measuring the weight of 100% ethyl alcohol expelled from six BD Insulin syringes with varying capacities or needle lengths. A one-way analysis assessed the variability between the dose delivery efficiency of 1mL, 0.5mL, and 0.3mL syringes. Testing indicated that the entire dose was delivered over 97.5% of the time for 1mL and 0.5mL syringes, but the autoinjector's loaded spring force and size exceeded structural limitations of 0.3mL or smaller syringes. Components can be manufactured in about twelve hours using an open-source desktop RepRap-class fused filament 3-D printer. The construction requires two compression springs and 3-D printed parts. The total material cost of CAD$6.83 is less than a tenth of comparable commercial autoinjectors, which makes this approach promising. The autoinjector, however, is a class two medical device and must be approved by regulators. Future work is needed to make distributed manufacturing of such medical devices feasible and reliable to support individuals burdened by healthcare costs.

Vaporized nicotine use among patients in HIV care who smoke tobacco: perceived health effects and effectiveness as a smoking cessation tool.

Evidence suggests adverse health effects from vaporized nicotine (VN) use, such as electronic "e" cigarettes, and limited efficacy to aid tobacco cessation. People with HIV (PWH) smoke tobacco at higher rates than the general population, with greater morbidity, highlighting the necessity of effective tobacco cessation tools. PWH may be more vulnerable to adverse effects of VN. Using semi-structured 1:1 interviews, we examined health beliefs regarding VN, patterns of use, and perceived effectiveness for tobacco cessation among PWH in HIV care at three geographically diverse U.S. sites. PWH (n = 24) had limited understanding of VN product content or health effects, presuming VN less harmful than tobacco cigarettes (TC). VN failed to adequately replicate the psychoactive effects or desired ritual of smoking TC. Concurrent TC use, and continuous VN use throughout the day, was common. Satiety using VN was elusive, and consumption quantity was difficult to track. VN had limited desirability and durability as a TC cessation tool among the interviewed PWH.

Methane in aquifers and alluvium overlying a coal seam gas region: Gas concentrations and isotopic differentiation.

The detection and attribution of methane in aquifers overlying oil and gas reservoirs has recently gained increasing attention internationally. The Surat Basin, in the Great Artesian Basin (GAB), Australia, hosts a coal seam gas (CSG) reservoir, with feedlots, town water supply, mines and agriculture that extract groundwater from aquifers that underly and overly the gas reservoir. This study aimed to use a multi-isotopic approach to differentiate biogenic methane generated in situ in GAB aquifers and the Condamine Alluvium, from the biogenic CSG produced from the underlying Walloon Coal Measures reservoir, to understand if gas had migrated or not. Dissolved methane (0.001 to 160 mg/l) and total methane concentrations (up to 91,818 ppmv) were measured using closed sampling methods and were higher than from open direct fill sampling (<0.001 to 25.4 mg/l), especially in gassy bores that contain dissolved methane above 10 to 13 mg/l. The CSG production waters and a gassy overlying aquifer bore had the most depleted water isotopes, and also the most enriched δ13C-DIC indicating strong methanogenesis. The majority of aquifers have isotopic signatures (δ13C-DIC, CH4 and CO2) indicating in situ methane production by primary CO2 reduction or fermentation, distinct from secondary microbial CO2 reduction in the CSG reservoir. Fractionation factors support methane production mainly via CO2 reduction, with fermentation in a subset of aquifer samples. The gas wetness parameters (636 to 20,000) are consistent with mainly microbial gases, with low dissolved ethane (max 0.04 mg/l). The majority of aquifer and alluvium samples in this study are consistent with in situ methane production, not migration, however in several gassy bores the methane source could not be clearly identified. This study is broadly applicable to understanding methane sources in aquifers overlying CSG reservoirs.

CELPI: trial protocol for a randomised controlled trial of a Carer End of Life Planning Intervention in people dying with dementia.

BACKGROUND: Dementia is a leading cause of death in developed nations. Despite an often distressing and symptom laden end of life, there are systematic barriers to accessing palliative care in older people dying of dementia. Evidence exists that 70% of people living with severe dementia attend an emergency department (ED) in their last year of life. The aim of this trial is to test whether a Carer End of Life Planning Intervention (CELPI), co-designed by consumers, clinicians and content specialists, improves access to end of life care for older people with severe dementia, using an ED visit as a catalyst for recognising unmet needs and specialist palliative care referral where indicated. METHODS: A randomised controlled trial (RCT) enrolling at six EDs across three states in Australia will be conducted, enrolling four hundred and forty dyads comprising a person with severe dementia aged ≥ 65 years, and their primary carer. Participants will be randomly allocated to CELPI or the control group. CELPI incorporates a structured carer needs assessment and referral to specialist palliative care services where indicated by patient symptom burden and needs assessment. The primary outcome measure is death of the person with dementia in the carer-nominated preferred location. Secondary outcomes include carer reported quality of life of the person dying of dementia, hospital bed day occupancy in the last 12 months of life, and carer stress. An economic evaluation from the perspective of a health funder will be conducted. DISCUSSION: CELPI seeks to support carers and provide optimal end of life care for the person dying of dementia. This trial will provide high level evidence as to the clinical and cost effectiveness of this intervention. TRIAL REGISTRATION: ACTRN12622000611729 registered 22/04/2022.

Open source surgical fracture table for digitally distributed manufacturing.

Roughly a third of the surgical procedures the World Bank is prioritizing as essential and cost-effective are orthopedic procedures. Yet in much of the developing world, prohibitive costs are a substantial barrier to universal access. One area where this is clear is surgical fracture tables, which generally cost >US$200,000 new. With the advent of 3-D printing, a new way to reduce medical equipment costs is to use open source hardware licensed designs to fabricate digitally-distributed manufactured medical hardware. That approach is applied here to make surgical tables more accessible. This study describes the design and manufacture of an open source surgical fracture table that uses materials that are widely available worldwide with specialty components being 3-D printed. The bill of materials and assembly instructions are detailed and the fracture table is validated to perform mechanically to specifications. Using an open source desktop RepRap-class 3-D printer, the components can be printed in a little over a week of continuous printing. Including the 3-D printed parts, the open source fracture table can be constructed for under US$3,000 in material costs, representing a 98.5% savings for commercial systems, radically increasing accessibility. The open source table can be adjusted 90-116 cm in height, tilted from +/-15 degrees, the leg height ranges from 31 to 117 cm, the arm supports and foot holder both have a 180-degree range, the foot position has a 54 cm range, and the legs can be adjusted from 55 to 120 degrees. It is mechanically adjusted so does not require electricity, however, surgical staff need to be trained on how to perform needed adjustments during surgery. The open source surgical table has verified performance for mechanical loading over 130 kg, geometric flexibility to allow for wide array of common surgeries, is radiolucent in surgical zones, and is modular and upgradeable.

Overcoming supply disruptions during pandemics by utilizing found hardware for open source gentle ventilation.

This article details the design of an open source emergency gentle ventilator (gentle-vent) framework that can be used in periods of scarcity. Although it is not a medical device, the system utilizes a wide range of commonly-available components that are combined using basic electronics skills to achieve the desired performance. The main function of the gentle-vent is to generate a calibrated pressure wave at the pump to provide support to the patient's breathing. Each gentle-vent permutation was tested using a DIY manometer as it would be utilized in the field in low-resource settings and validated with an open source VentMon. The most rudimentary implementation costs less than $40.

Open source software toolchain for automated non-targeted screening for toxins in alternative foods.

Previous published methods for non-targeted screening of toxins in alternative foods such as leaf concentrate, agricultural residues or plastic fed to biological consortia are time consuming and expensive and thus present accessibility, as well as, time-constraint issues for scientists from under resourced settings to identify safe alternative foods. The novel methodology presented here, utilizes a completely free and open source software toolchain for automatically screening unknown alternative foods for toxicity using experimental data from ultra-high-pressure liquid chromatography and mass spectrometry. The process uses three distinct tools (mass spectrometry analysis with MZmine 2, formula assignment with MFAssignR, and data filtering with ToxAssign) enabling it to be modular and easily upgradable in the future. MZmine 2 and MFAssignR have been previously described, while ToxAssign was developed here to match the formulas output by formula assignment to potentially toxic compounds in a local table, then look up toxic data on the Open Food Tox Database for the matched compounds. This process is designed to fill the gap between food safety analysis techniques and developing alternative food production techniques to allow for new methods of food production to be preliminarily tested before animal testing. The methodology was validated against a previous method using proprietary commercial software. The new process identifies all of the toxic elements the previous process identified with more detailed information than the previous process was able to provide automatically.•Efficient analysis to find potentially toxic compounds in alternative foods and resilient foods.•Identification of potentially unsafe products without the use of live animal testing.•Modular free and open source design to allow for upgrading or fitting of user needs.

Associations between behaviour and health outcomes in conventional and slow-growing breeds of broiler chicken.

Broiler chickens are prone to a range of complex health and welfare issues. To support informed selection of welfare traits whilst minimising impact on production efficiency and to address a major gap in understanding, we systematically explored associations between health and behavioural indicators of broiler welfare. One conventional (CNV, n = 350) and two slow-growing broiler breeds (SGH and SGN, respectively n = 400) were reared from hatch in pens of 50 birds. Birds were assessed for health (gait, plumage cover and dirtiness, pododermatitis, hockburn, and leg deviations) at 2.2 kg liveweight according to the Royal Society for the Prevention of Cruelty to Animals Broiler Breed Welfare Assessment Protocol. Behaviour and resource-use of 10% of birds per pen, on days 29 (all breeds) and 43 (SGH and SGN), was (i) scan sampled every 60 min between three to six and between twelve to fifteen hours after photoperiod onset; and (ii) continuously sampled sequentially from focal birds for 3 min each in a random order, during 15 min observation periods at three and twelve hours after photoperiod onset. Binary logistic generalized linear models were used, to assess respective associations between pen prevalence of each health outcome and (i) pen mean percentage scans of behaviour, and (ii) pen mean frequency and duration per 3 min focal observation of behaviour. Better growth rate and feed conversion but poorer health outcomes (mortality, gait, pododermatitis, feather cover) were more prevalent in CNV. Strong associations between behaviour and several heath indicators revealed, (i) increases in side-lying inactive, sitting inactive, and use of the litter relative to other resources, as primary and general indicators of poorer health, and (ii) increases in standing inactive, perch use, walking, Comfort, High Energy and Exploratory behaviour as primary and general indicators of better health. Of these, changes in side-lying, standing inactive, walking, Comfort and High Energy behaviour were particularly sensitive to small differences in health outcomes important for breed acceptance in high-welfare schemes. Crucially these behavioural measures additionally represent motivational and affective aspects of welfare not captured by health measures and allow opportunity for earlier intervention. Thus, to provide a comprehensive assessment of broiler experience, behaviour should be incorporated into broiler welfare assessments.

A philosophical history of programmatic assessment: tracing shifting configurations.

Programmatic assessment is now well entrenched in medical education, allowing us to reflect on when it first emerged and how it evolved into the form we know today. Drawing upon the intellectual tradition of historical epistemology, we provide a philosophically-oriented historiographical study of programmatic assessment. Our goal is to trace its relatively short historical trajectory by describing shifting configurations in its scene of inquiry-focusing on questions, practices, and philosophical presuppositions. We identify three historical phases: emergence, evolution and entrenchment. For each, we describe the configurations of the scene; examine underlying philosophical presuppositions driving changes; and detail upshots in assessment practice. We find that programmatic assessment emerged in response to positivist 'turmoil' prior to 2005, driven by utility considerations and implicit pragmatist undertones. Once introduced, it evolved with notions of diversity and learning being underscored, and a constructivist ontology developing at its core. More recently, programmatic assessment has become entrenched as its own sub-discipline. Rich narratives have been emphasised, but philosophical underpinnings have been blurred. We hope to shed new light on current assessment practices in the medical education community by interrogating the history of programmatic assessment from this philosophical vantage point. Making philosophical presuppositions explicit highlights the perspectival nature of aspects of programmatic assessment, and suggest reasons for perceived benefits as well as potential tensions, contradictions and vulnerabilities in the approach today. We conclude by offering some reflections on important points to emerge from our historical study, and suggest 'what next' for programmatic assessment in light of this endeavour.

Hip fractures in centenarians: a multicentre review of outcomes.

INTRODUCTION: Advances in healthcare have resulted in an increasing UK population, with the proportion of elderly individuals expanding significantly, including centenarians. Hospitals can expect to see growing numbers of so-called 'super-elderly' patients with trauma, a majority of whom will have hip fractures. We performed a multicentre review of hip fracture outcomes in centenarians to assess whether being an outlier in age correlates with poorer prognosis. METHODS: Centenarians admitted to Basingstoke, Southampton, Dorset, and Salisbury district hospitals with hip fractures between January 2014 and June 2019 were included. Electronic records were searched to obtain demographics, functional status, and admission details. RESULTS: A total of 60 centenarians were included, with a median age of 101 years (range 100-108 years), 85% of whom were female; 29 were admitted from their own home or sheltered housing and 31 from nursing or residential care; 33 had some outdoor mobility, 26 only mobilised indoors, and 1 had no mobility. Common comorbidities were renal and heart disease and dementia. Of the total, 56 underwent surgery, 51 within 36 hours. In terms of accommodation, 63.4% returned to their pre-injury level of independence. At 30 days, three months, and one year, mortality rates were 27% (n = 16), 40% (n = 24) and 55% (n = 33), respectively. CONCLUSION: Trauma in the elderly population is an area of growing interest, yet few studies address centenarians with hip fractures. This work demonstrates that mortality rates within one year of injury were high, but almost half survived beyond a year. Two-thirds of patients regained their pre-injury level of independence, suggesting that functional recovery may not be as poor as previously reported.

Pourfour du Petit (1664-1741).

François Pourfour du Petit was a Parisian experimental neuro-anatomist, and ophthalmologist, who investigated his extensive wartime experiences of brain and spinal injuries and verified his conclusions by animal experiments. His results showed with great originality that brain injuries caused weakness or paralysis of the opposite limbs. He also clarified the anatomy of the spinal cord and decussation of the pyramidal tracts, and demonstrated the anatomy and clinical significance of the cervical sympathetic chain.

Menthol as an Ergogenic Aid for the Tokyo 2021 Olympic Games: An Expert-Led Consensus Statement Using the Modified Delphi Method.

INTRODUCTION: Menthol topical application and mouth rinsing are ergogenic in hot environments, improving performance and perception, with differing effects on body temperature regulation. Consequently, athletes and federations are beginning to explore the possible benefits to elite sport performance for the Tokyo 2021 Olympics, which will take place in hot (~ 31 °C), humid (70% RH) conditions. There is no clear consensus on safe and effective menthol use for athletes, practitioners, or researchers. The present study addressed this shortfall by producing expert-led consensus recommendations. METHOD: Fourteen contributors were recruited following ethical approval. A three-step modified Delphi method was used for voting on 96 statements generated following literature consultation; 192 statements total (96/96 topical application/mouth rinsing). Round 1 contributors voted to "agree" or "disagree" with statements; 80% agreement was required to accept statements. In round 2, contributors voted to "support" or "change" their round 1 unaccepted statements, with knowledge of the extant voting from round 1. Round 3 contributors met to discuss voting against key remaining statements. RESULTS: Forty-seven statements reached consensus in round 1 (30/17 topical application/rinsing); 14 proved redundant. Six statements reached consensus in round 2 (2/4 topical application/rinsing); 116 statements proved redundant. Nine further statements were agreed in round 3 (6/3 topical application/rinsing) with caveats. DISCUSSION: Consensus was reached on 62 statements in total (38/24 topical application/rinsing), enabling the development of guidance on safe menthol administration, with a view to enhancing performance and perception in the heat without impairing body temperature regulation.

Limiting liability with positioning to minimize negative health effects of cellular phone towers.

The use of cellular phones is now ubiquitous through most of the adult global population and is increasingly common among even young children in many countries (e.g. Finland, where the market for smart phones is nearly saturated). The basic operation of cellular phone networks demands widespread human exposure to radio-frequency radiation (RFR) with cellular phone base stations providing cellular coverage in most areas. As the data needs of the population increase from the major shift in the source of Internet use from personal computers to smart phones, this coverage is widely predicted to increase. Thus, both the density of base stations and their power output is expected to increase the global human RFR exposure. Although direct causation of negative human health effects from RFR from cellular phone base stations has not been finalized, there is already enough medical and scientific evidence to warrant long-term liability concerns for companies deploying cellular phone towers. In order to protect cell phone tower firms from the ramifications of the failed paths of other industries that have caused unintended human harm (e.g. tobacco) this Current Issue summarizes the peer-reviewed literature on the effects of RFR from cellular phone base stations. Specifically the impacts of siting base stations are closely examined and recommendations are made for companies that deploy them to minimize their potential future liability.

Erratum: Frequency of heavy vehicle traffic and association with DNA methylation at age 18 years in a subset of the Isle of Wight birth cohort.

[This corrects the article DOI: 10.1093/eep/dvy028.][This corrects the article DOI: 10.1093/eep/dvy028.].

The "split brain" and Roger Wolcott Sperry (1913-1994).

The concepts of cerebral localization were established in the early 19th century. From these arose the idea that the dominant (usually left) hemisphere mainly subserved functions of cognition and language. The "relatively retarded right hemisphere" by contrast was mute, agraphic, apraxic, and lacking generally in higher cognitive function. This essay sketches the import of the work of Sperry and colleagues on patients subjected to callosal section eg., "split brain". They showed that the minor hemisphere possessed considerable capacity for cognitive understanding and language. His Nobel prize-winning "Split-Brain Experiments"confirmed the role of the corpus callosum in interhemispheric transfer of information.

Education Research: Neuroradiology curriculum in neurology residency training programs: How we teach neuroimaging.

OBJECTIVE: To better understand how the essential skill of interpreting various neuroimaging studies is taught to neurology residents in Accreditation Council for Graduate Medical Education (ACGME)-accredited training programs. METHODS: A 22-question survey was sent electronically to 150 ACGME adult neurology program directors. We collected data regarding the presence of a neuroimaging curriculum, frequency of review sessions and testing, resource availability, and program director confidence in neuroimaging skills of graduating residents. We collected average scores on the neuroimaging section of the Resident In-service Training Examination of graduating residents for the past 3 years, which we attempted to correlate with resource availability. RESULTS: One-third of neurology residency programs do not have a neuroimaging curriculum, and half of training programs do not require a neuroimaging rotation. On average, trainees spend 1 hour per week reviewing imaging with radiologists. Program directors believed trainees receive insufficient neuroimaging training, with a median satisfaction rating on a Likert scale (0-100) of 35 (interquartile range 27-47). Few programs take advantage of online training resources. CONCLUSION: Opportunities exist to improve neuroimaging education in neurology resident education. This can be done by closer adherence to the American Academy of Neurology neuroimaging curriculum guidelines, especially by expanding access to online resources and additional emphasis on imaging review with neurology subspecialists.

Multivariate Air Pollution Prediction Modeling with partial Missingness.

Missing observations from air pollution monitoring networks have posed a longstanding problem for health investigators of air pollution. Growing interest in mixtures of air pollutants has further complicated this problem, as many new challenges have arisen that require development of novel methods. The objective of this study is to develop a methodology for multivariate prediction of air pollution. We focus specifically on tackling different forms of missing data, such as: spatial (sparse sites), outcome (pollutants not measured at some sites), and temporal (varieties of interrupted time series). To address these challenges, we develop a novel multivariate fusion framework, which leverages the observed inter-pollutant correlation structure to reduce error in the simultaneous prediction of multiple air pollutants. Our joint fusion model employs predictions from the Environmental Protection Agency's Community Multiscale Air Quality (CMAQ) model along with spatio-temporal error terms. We have implemented our models on both simulated data and a case study in South Carolina for 8 pollutants over a 28-day period in June 2006. We found that our model, which uses a multivariate correlated error in a Bayesian framework, showed promising predictive accuracy particularly for gaseous pollutants.