Outcomes of an expedited same-day discharge protocol following cardiac implantable electronic device (CIED) implantation.

BACKGROUND: With increasing constraints on healthcare resources, greater attention is being focused on improved resource utilization. Prior studies have demonstrated safety of same-day discharge following CIED implantation but are limited by vague protocols with long observation periods. In this study, we evaluate the safety of an expedited 2 hour same-day discharge protocol following CIED implantation. METHODS: Patients undergoing CIED implantation at three centers between 2015 and 2021 were included. Procedural, demographic, and adverse event data were abstracted from the electronic health record. Patients were divided into same-day discharge (SDD) and delayed discharge (DD) cohorts. The primary outcome was complications including lead malfunction requiring revision, pneumothorax, hemothorax, lead dislodgement, lead perforation with tamponade, and mortality within 30 days of procedure. Outcomes were compared between the two cohorts using the χ2 test. RESULTS: A total of 4543 CIED implantation procedures were included with 1557 patients (34%) in the SDD cohort. SDD patients were comparatively younger, were more likely to be male, and had fewer comorbidities than DD patients. Among SDD patients, the mean time to post-operative chest X-ray was 2.6 h. SDD had lower rates of complications (1.3% vs 2.1%, p = 0.0487) and acute care utilization post-discharge (9.6% vs 14.0%, p < 0.0001). There was no difference in the 90-day infection rate between the cohorts. CONCLUSIONS: An expedited 2 hour same-day discharge protocol is safe and effective with low rates of complications, infection, and post-operative acute care utilization.

Testing the effectiveness of interactive training on sexual harassment and assault in field science.

Fieldwork is a critical tool for scientific research, particularly in applied disciplines. Yet fieldwork is often unsafe, especially for members of historically marginalized groups and people whose presence in scientific spaces threatens traditional hierarchies of power, authority, and legitimacy. Research is needed to identify interventions that prevent sexual harassment and assault from occurring in the first place. We conducted a quasi-experiment assessing the impacts of a 90-min interactive training on field-based staff in a United States state government agency. We hypothesized that the knowledge-based interventions, social modeling, and mastery experiences included in the training would increase participants' sexual harassment and assault prevention knowledge, self-efficacy, behavioural intention, and behaviour after the training compared to a control group of their peers. Treatment-control and pre-post training survey data indicate that the training increased participants' sexual harassment and assault prevention knowledge and prevention self-efficacy, and, to a lesser extent, behavioural intention. These increases persisted several months after the training for knowledge and self-efficacy. While we did not detect differences in the effect of the training for different groups, interestingly, post-hoc tests indicated that women and members of underrepresented racial groups generally scored lower compared to male and white respondents, suggesting that these groups self-assess their own capabilities differently. Finally, participants' likelihood to report incidents increased after the training but institutional reports remained low, emphasizing the importance of efforts to transform reporting systems and develop better methods to measure bystander actions. These results support the utility of a peer-led interactive intervention for improving workplace culture and safety in scientific fieldwork settings. PROTOCOL REGISTRATION: "The stage 1 protocol for this Registered Report was accepted in principle on August 24, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.21770165 .

Structural and functional damage to neuronal nuclei caused by extracellular tau oligomers.

INTRODUCTION: Neuronal nuclei are normally smoothly surfaced. In Alzheimer's disease (AD) and other tauopathies, though, they often develop invaginations. We investigated mechanisms and functional consequences of neuronal nuclear invagination in tauopathies. METHODS: Nuclear invagination was assayed by immunofluorescence in the brain, and in cultured neurons before and after extracellular tau oligomer (xcTauO) exposure. Nucleocytoplasmic transport was assayed in cultured neurons. Gene expression was investigated using nanoString nCounter technology and quantitative reverse transcription polymerase chain reaction. RESULTS: Invaginated nuclei were twice as abundant in human AD as in cognitively normal adults, and were increased in mouse neurodegeneration models. In cultured neurons, nuclear invagination was induced by xcTauOs by an intracellular tau-dependent mechanism. xcTauOs impaired nucleocytoplasmic transport, increased histone H3 trimethylation at lysine 9, and altered gene expression, especially by increasing tau mRNA. DISCUSSION: xcTauOs may be a primary cause of nuclear invagination in vivo, and by extension, impair nucleocytoplasmic transport and induce pathogenic gene expression changes. HIGHLIGHTS: Extracellular tau oligomers (xcTauOs) cause neuronal nuclei to invaginate. xcTauOs alter nucleocytoplasmic transport, chromatin structure, and gene expression. The most upregulated gene is MAPT, which encodes tau. xcTauOs may thus drive a positive feedback loop for production of toxic tau.

Outcomes of a Remote Cardiac Rehabilitation Program for Patients Undergoing Atrial Fibrillation Ablation: Pilot Study.

BACKGROUND: Risk factor modification, in particular exercise and weight loss, has been shown to improve outcomes for patients with atrial fibrillation (AF). However, access to structured supporting programs is limited. Barriers include the distance from appropriate facilities, insurance coverage, work or home responsibilities, and transportation. Digital health technology offers an opportunity to address this gap and offer scalable interventions for risk factor modification. OBJECTIVE: This study aims to assess the feasibility and effectiveness of a 12-week asynchronous remotely supervised exercise and patient education program, modeled on cardiac rehabilitation programs, in patients with AF. METHODS: A total of 12 patients undergoing catheter ablation of AF were enrolled in this pilot study. Participants met with an exercise physiologist for a supervised exercise session to generate a personalized exercise plan to be implemented over the subsequent 12-week program. Disease-specific education was also provided as well as instruction in areas such as blood pressure and weight measurement. A digital health toolkit for self-tracking was provided to facilitate monitoring of exercise time, blood pressure, weight, and cardiac rhythm. The exercise physiologist remotely monitored participants and completed weekly check-ins to titrate exercise targets and provide further education. The primary end point was program completion. Secondary end points included change in self-tracking adherence, weight, 6-minute walk test (6MWT), waist circumference, AF symptom score, and program satisfaction. RESULTS: The median participant age was 67.5 years, with a mean BMI of 33.8 kg/m2 and CHADs2VASC (Congestive Heart Failure, Hypertension, Age [≥75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female]) of 1.5. A total of 11/12 (92%) participants completed the program, with 94% of expected check-ins completed and 2.9 exercise sessions per week. Adherence to electrocardiogram and blood pressure tracking was fair at 81% and 47%, respectively. Significant reductions in weight, waist circumference, and BMI were observed with improvements in 6MWT and AF symptom scores (P<.05) at the completion of the program. For program management, a mean of 2 hours per week or 0.5 hours per patient per week was required, inclusive of time for follow-up and intake visits. Participants rated the program highly (>8 on a 10-point Likert scale) in terms of the impact on health and wellness, educational value, and sustainability of the personal exercise program. CONCLUSIONS: An asynchronous remotely supervised exercise program augmented with AF-specific educational components for patients with AF was feasible and well received in this pilot study. While improvements in patient metrics like BMI and 6MWT are encouraging, they should be viewed as hypothesis generating. Based on insights gained, future program iterations will include particular attention to improved technology for data aggregation, adjustment of self-monitoring targets based on observed adherence, and protocol-driven exercise titration. The study design will need to incorporate strategies to facilitate the recruitment of a diverse and representative participant cohort.

Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.

Effect of Anionic Lipids on Mammalian Plasma Cell Membrane Properties.

The effect of lipid composition on models of the inner leaflet of mammalian cell membranes has been investigated. Grazing incidence X-ray diffraction and X-ray and neutron reflectivity have been used to characterize lipid packing and solvation, while electrochemical and infrared spectroscopic methods have been employed to probe phase behavior in an applied electric field. Introducing a small quantity of the anionic lipid dimyristoylphosphatidylserine (DMPS) into bilayers of zwitterionic dimyristoylphosphatidylethanolamine (DMPE) results in a significant change in the bilayer response to an applied field: the tilt of the hydrocarbon chains increases before returning to the original tilt angle on detachment of the bilayer. Equimolar mixtures, with slightly closer chain packing, exhibit a similar but weaker response. The latter also tend to incorporate more solvent during this electrochemical phase transition, at levels similar to those of pure DMPS. Reflectivity measurements reveal greater solvation of lipid layers for DMPS > 30 mol %, matching the greater propensity for DMPS-rich bilayers to incorporate water. Taken together, the data indicate that the range of 10-35 mol % DMPS provides optimum bilayer properties (in flexibility and function as a barrier), which may explain why the DMPS content of cell membranes tends to be found within this range.

One size does not fit all: diversity of length-force properties of obliquely striated muscles.

Obliquely striated muscles occur in 17+ phyla, likely evolving repeatedly, yet the implications of oblique striation for muscle function are unknown. Contrary to the belief that oblique striation allows high force output over extraordinary length ranges (i.e. superelongation), recent work suggests diversity in operating length ranges and length-force relationships. We hypothesize oblique striation evolved to increase length-force relationship flexibility. We predict that superelongation is not a general characteristic of obliquely striated muscles and instead that length-force relationships vary with operating length range. To test these predictions, we measured length-force relationships of five obliquely striated muscles from inshore longfin squid, Doryteuthis pealeii: tentacle, funnel retractor and head retractor longitudinal fibers, and arm and fin transverse fibers. Consistent with superelongation, the tentacle length-force relationship had a long descending limb, whereas all others exhibited limited descending limbs. The ascending limb at 0.6P0 was significantly broader (P<0.001) for the tentacle length-force relationship (0.43±0.04L0; where L0 is the preparation length that produced peak isometric stress, P0) than for the arm (0.29±0.03L0), head retractor (0.24±0.06L0), fin (0.20±0.04L0) and funnel retractor (0.27±0.03L0). The fin's narrow ascending limb differed significantly from those of the arm (P=0.004) and funnel retractor (P=0.012). We further characterized the tentacle preparation's maximum isometric stress (315±78 kPa), maximum unloaded shortening velocity (2.97±0.55L0 s-1) and ultrastructural traits (compared with the arm), which may explain its broader length-force relationship. Comparison of obliquely striated muscles across taxa revealed length-force relationship diversity, with only two species exhibiting superelongation.

Risk factors for postoperative hypotension after adrenalectomy for phaeochromocytoma: derivation of the PACS risk score.

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Vectored jets power arms-first and tail-first turns differently in brief squid with assistance from fins and keeled arms.

Squids maneuver to capture prey, elude predators, navigate complex habitats and deny rivals access to mates. Despite the ecological importance of this essential locomotive function, limited quantitative data on turning performance and wake dynamics of squids are available. To better understand the contribution of the jet, fins and arms to turns, the role of orientation (i.e. arms first versus tail first) in maneuvering, and the relationship between jet flow and turning performance, kinematic and 3D velocimetry data were collected in tandem from brief squid, Lolliguncula brevis. The pulsed jet, which can be vectored to direct flows, was the primary driver of most turning behaviors, producing flows with the highest impulse magnitude and angular impulse about the main axis of the turn (yaw) and secondary axes (roll and pitch). The fins and keeled arms played subordinate but important roles in turning performance, contributing to angular impulse, stabilizing the maneuver along multiple axes and/or reducing rotational resistance. Orientation affected turning performance and dynamics, with tail-first turns being associated with greater impulse and angular impulse, longer jet structures, higher jet velocities and greater angular turning velocities than arms-first turns. Conversely, arms-first turns involved shorter, slower jets with less impulse, but these directed short pulses resulted in lower minimum length-specific turning radii. Although the length-to-diameter ratio (L/D) of ejected jet flow was a useful metric for characterizing vortical flow features, it, by itself, was not a reliable predictor of angular velocity or turning radii, which reflects the complexity of the squid multi-propulsor system.

A compact instrument for gamma-ray burst detection on a CubeSat platform II: Detailed design, assembly and validation.

The Gamma-ray Module, GMOD, is a miniaturised novel gamma-ray detector which will be the primary scientific payload on the Educational Irish Research Satellite (EIRSAT-1) 2U CubeSat mission. GMOD comprises a compact (25 mm × 25 mm × 40 mm) cerium bromide scintillator coupled to a tiled array of 4 × 4 silicon photomultipliers, with front-end readout provided by the IDE3380 SIPHRA. This paper presents the detailed GMOD design and the accommodation of the instrument within the restrictive CubeSat form factor. The electronic and mechanical interfaces are compatible with many off-the-shelf CubeSat systems and structures. The energy response of the GMOD engineering qualification model has been determined using radioactive sources, and an energy resolution of 5.4% at 662 keV has been measured. EIRSAT-1 will perform on-board processing of GMOD data. Trigger results, including light-curves and spectra, will be incorporated into the spacecraft beacon and transmitted continuously. Inexpensive hardware can be used to decode the beacon signal, making the data accessible to a wide community. GMOD will have scientific capability for the detection of gamma-ray bursts, in addition to the educational and technology demonstration goals of the EIRSAT-1 mission. The detailed design and measurements to date demonstrate the capability of GMOD in low Earth orbit, the scalability of the design for larger CubeSats and as an element of future large gamma-ray missions.

A randomised, open-label, cross-over clinical study to evaluate the pharmacokinetic, pharmacodynamic and safety and tolerability profiles of tobacco-free oral nicotine pouches relative to cigarettes.

RATIONALE: Tobacco harm reduction (THR) involves encouraging adult smokers who would otherwise continue to smoke to transition to less harmful forms of nicotine delivery. These products must offer adult smokers reduced exposure to chemicals associated with tobacco combustion, satisfactory blood plasma nicotine levels and serve as an acceptable alternative. The most recent THR innovation is tobacco-free oral nicotine pouches. OBJECTIVES: This study aimed to compare pharmacokinetic, pharmacodynamic and safety and tolerability profiles of two nicotine pouch variants (ZoneX #2 (5.8 mg nicotine/pouch); ZoneX #3 (10.1 mg nicotine/pouch)) with cigarette to assess the pouches' THR potential. METHODS: This was a controlled use, randomised, open-label, cross-over clinical study with 24 healthy adult traditional tobacco users. Pharmacokinetic (plasma nicotine levels; up to 8 h post-use), pharmacodynamic (urge to smoke, product liking; up to 4 h post-use) and short-term safety and tolerability profiles were assessed. RESULTS: Distinct nicotine pouch pharmacokinetic profiles indicated nicotine absorption via the oral mucosa. Plasma nicotine levels were lower, and time to peak slower, for the nicotine pouches compared to cigarette (Cmax cigarette: 11.6 ng/ml vs. #2: 5.2 ng/ml, p < 0.0001; #3: 7.9 ng/ml, p < 0.0003) (Tmax cigarette: 8.6 min vs. #2: 26 min; #3: 22 min). All products effectively reduced subjects' urge to smoke and presented favourable product liking scores; nicotine pouches were also well tolerated following short-term use (no serious adverse events). CONCLUSIONS: Overall, the assessed ZoneX nicotine pouches may offer an acceptable alternative for adult smokers to achieve satisfactory levels of nicotine delivery and, based on the pharmacokinetic parameters and under the study conditions, likely have a lower abuse liability and addictive potential for current adult smokers compared to continued cigarette smoking. CLINICAL TRIAL IDENTIFIER: NCT04891406 (clinicaltrials.gov).

Inequities in Telehealth Use Associated with Payer Type During the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has prompted a shift in health care delivery and compelled a heavier reliance on telehealth. The objective of this study was to determine if differences in coverage policies by payer type resulted in differential telehealth use during the first 3 months of the COVID-19 pandemic. In this population-based cohort study of low-income Arkansans, Medicaid beneficiaries enrolled in the traditional Primary Care Case Management (PCCM) program were compared with Medicaid beneficiaries covered through premium assistance in private Qualified Health Plans (QHPs). Methods: A retrospective review was conducted of insurance claims records from June 1, 2019, to June 30, 2020, for synchronous telehealth and mobile health (m-health) visits, as well as other forms of telehealth. To establish the baseline equivalence of enrollees in the two groups, propensity score matching design was used on demographic and geographic characteristics, Charlson Comorbidity Index, broadband availability, and prior service utilization. Results: Compared with enrollees in the PCCM program, Medicaid expansion enrollees in QHPs had higher odds of having had at least one telehealth visit (adjusted odds ratio [aOR] = 1.35, 95% confidence interval [CI]: 1.29-1.42) during the early phase of the COVID-19 pandemic. Categorizing utilizations by domain, QHP enrollees were more likely to use synchronous telehealth (aOR = 1.31; 95% CI: 1.25-1.37) and m-health (aOR = 5.91; 95% CI: 4.25-8.21). A higher proportion of QHP enrollees also had at least one mental or behavioral health telehealth session (aOR = 1.13; 95% CI: 1.07-1.19). Conclusions: Our study demonstrated that within low-income populations, payer type was associated with inequitable access to telehealth during the early phase of the COVID-19 pandemic.

E-Cigarette Aerosol Deposition and Disposition of [11C]Nicotine Using Positron Emission Tomography: A Comparison of Nicotine Uptake in Lungs and Brain Using Two Different Nicotine Formulations.

Smoking is a cause of serious disease in smokers. Electronic cigarettes, delivering aerosolized nicotine, offer adult smokers a potentially less harmful alternative to combustible cigarettes. This explorative PET/CT study investigated the distribution and deposition of inhaled [11C]nicotine using the mybluTM e-cigarette with two nicotine formulations, freebase and lactate salt. Fifteen healthy adult smokers participated in the two-part study to assess the distribution and accumulation of [11C]nicotine in the respiratory pathways and brain. Time-activity data for the respiratory pathways, lungs, oesophagus and brain were derived. 31-36% of both inhaled tracer formulations accumulated in the lung within 15-35 s. [11C]Nicotinefreebase exhibited higher uptake and deposition in the upper respiratory pathways. For [11C]nicotinelactate, brain deposition peaked at 4-5%, with an earlier peak and a steeper decline. A different kinetic profile was obtained for [11C]nicotinelactate with lower tracer uptake and accumulation in the upper respiratory pathways and an earlier peak and a steeper decline in lung and brain. Using nicotine lactate formulations in e-cigarettes may thus contribute to greater adult smoker acceptance and satisfaction compared to freebase formulations, potentially aiding a transition from combustible cigarettes and an acceleration of tobacco harm reduction initiatives.

SARS-CoV-2 Incidence in K-12 School Districts with Mask-Required Versus Mask-Optional Policies - Arkansas, August-October 2021.

Masks are effective at limiting transmission of SARS-CoV-2, the virus that causes COVID-19 (1), but the impact of policies requiring masks in school settings has not been widely evaluated (2-4). During fall 2021, some school districts in Arkansas implemented policies requiring masks for students in kindergarten through grade 12 (K-12). To identify any association between mask policies and COVID-19 incidence, weekly school-associated COVID-19 incidence in school districts with full or partial mask requirements was compared with incidence in districts without mask requirements during August 23-October 16, 2021. Three analyses were performed: 1) incidence rate ratios (IRRs) were calculated comparing districts with full mask requirements (universal mask requirement for all students and staff members) or partial mask requirements (e.g., masks required in certain settings, among certain populations, or if specific criteria could not be met) with school districts with no mask requirement; 2) ratios of observed-to-expected numbers of cases, by district were calculated; and 3) incidence in districts that switched from no mask requirement to any mask requirement were compared before and after implementation of the mask policy. Mean weekly district-level attack rates were 92-359 per 100,000 persons in the community* and 137-745 per 100,000 among students and staff members; mean student and staff member vaccination coverage ranged from 13.5% to 18.6%. Multivariable adjusted IRRs, which included adjustment for vaccination coverage, indicated that districts with full mask requirements had 23% lower COVID-19 incidence among students and staff members compared with school districts with no mask requirements. Observed-to-expected ratios for full and partial mask policies were lower than ratios for districts with no mask policy but were slightly higher for districts with partial policies than for those with full mask policies. Among districts that switched from no mask requirement to any mask requirement (full or partial), incidence among students and staff members decreased by 479.7 per 100,000 (p<0.01) upon implementation of the mask policy. In areas with high COVID-19 community levels, masks are an important part of a multicomponent prevention strategy in K-12 settings (5).

Automation of hybridization and capture based next generation sequencing library preparation requires reduction of on-deck bead binding and heated wash temperatures.

Capture-based library preparation for next generation sequencing (NGS) offers a balance between sequencing depth and bioinformatics cost of analysis. Liquid handling automation enhances the reliability of the library preparation process by reducing sample-to-sample variation and substantially enhances throughput, particularly when it can be employed in a 'walk-away' fashion with limited hands-on interaction. This requires complex series of mixing and heating steps like those utilized in capture chemistries to happen on the liquid handler. While developing liquid handling automation for Integrated DNA Technologies (IDT) xGen Exome, Illumina TruSight Oncology 500, and Personal Genome Diagnostics (PGDx) elio Plasma Resolve chemistries on the PerkinElmer Sciclone liquid handler, we found that applying the capture temperatures recommended for manual library preparation results in low yield on automation. To restore the final library yield, we reduced bead binding and/or heated wash temperatures of the Peltier heaters on the liquid handlers by about 10°C. Since this applied across three unique capture-based chemistries, we consider this a generalizable principle of automating capture on the Sciclone. We hypothesize that this is driven by the very different thermodynamic environments represented by a sealed plate on a thermal cycler and a plate with a lid on a Peltier heater. This phenomenon should be considered when automating NGS library preparation on PerkinElmer Sciclone instruments.

Reductions in biomarkers of exposure to selected harmful and potentially harmful constituents following exclusive and partial switching from combustible cigarettes to myblu™ electronic nicotine delivery systems (ENDS).

Electronic nicotine delivery systems (ENDS) offer adult combustible cigarette smokers an alternative, potentially reduced harm, mode of nicotine delivery, attributed to fewer and reduced levels of harmful and potentially harmful constituents (HPHCs) in their aerosols compared to cigarette smoke. These two identical, randomised, open label, two-part studies aimed to compare levels of 15 biomarkers of exposure (BoE) to selected HPHCs associated with tobacco smoking in healthy US adult smoker subjects (n = 72). Following 9 days of exclusive use of a range of allocated myblu™ ENDS variants, subjects' levels of 14 non-nicotine BoE were substantially reduced compared to baseline values (combustible cigarette use), in the range of 46-97%. BoE reductions were sustained in subjects who continued myblu use exclusively (n = 25) for a further 5 days, and returned to near baseline levels in subjects who returned to exclusive combustible cigarette use (n = 21). Dual users (n = 24) demonstrated reductions in BoE to a lesser extent than with exclusive myblu use. Measured nicotine equivalents did not significantly change throughout the study. These data suggest exclusive use of ENDS provides adult smokers seeking an alternative to combustible cigarettes with substantial reductions in HPHC exposures whilst achieving satisfying levels of nicotine delivery. Dual use involving substitution of cigarettes may also provide some of this advantage, but to lesser extent. Overall, the data contribute to the weight of evidence that ENDS are an important tool in tobacco harm reduction for adult smokers unwilling to or uninterested in quitting smoking. Study 1: NCT04430634, study 2: NCT04429932, clinicaltrials.gov (10-06-2020).

A compact instrument for gamma-ray burst detection on a CubeSat platform I: Design drivers and expected performance.

The Educational Irish Research Satellite 1 (EIRSAT-1) is a 2U CubeSat being developed under ESA's Fly Your Satellite! programme. The project has many aspects, which are primarily educational, but also include space qualification of new detector technologies for gamma-ray astronomy and the detection of gamma-ray bursts (GRBs). The Gamma-ray Module (GMOD), the main mission payload, is a small gamma-ray spectrometer comprising a 25 mm × 25 mm × 40 mm cerium bromide scintillator coupled to an array of 16 silicon photomultipliers. The readout is provided by IDE3380 (SIPHRA), a low-power and radiation tolerant readout ASIC. GMOD will detect gamma-rays and measure their energies in a range from tens of keV to a few MeV. Monte Carlo simulations were performed using the Medium Energy Gamma-ray Astronomy Library to evaluate GMOD's capability for the detection of GRBs in low Earth orbit. The simulations used a detailed mass model of the full spacecraft derived from a very high-fidelity 3D CAD model. The sky-average effective area of GMOD on board EIRSAT-1 was found to be 10 cm2 at 120 keV. The instrument is expected to detect between 11 and 14 GRBs, at a significance greater than 10σ (and up to 32 at 5σ), during a nominal one-year mission. The shape of the scintillator in GMOD results in omni-directional sensitivity which allows for a nearly all-sky field of view.

Quantitative Assessment of Response to Long-Term Treatment with Intravenous Immunoglobulin in Patients with Stiff Person Syndrome.

BACKGROUND: Stiff person syndrome (SPS) is an autoimmune condition involving antibodies against several components of the inhibitory synapse in the spinal cord, with glutamic acid decarboxylase antibodies being the predominant immune marker. SPS affects approximately 1 patient per million population per year. The effect of intravenous immunoglobulin (IVIG) has been established, but studies on the long-term efficacy of regular IVIG are limited. OBJECTIVES: To review clinical details and long-term treatment response using a patient-reported questionnaire in SPS and related syndromes. METHODS: Patients were identified from a tertiary neuroimmunology clinic based on classical clinical symptoms, autoimmune profiles, and neurophysiological changes (Dalakas criteria). They were followed up after treatment to assess the response to IVIG. RESULTS: A total of 23 patients fulfilled the selection criteria. Patients' demographic profiles and clinical presentations were akin to that reported in literature. There was significant improvement in the functional ability (assessed by the modified Rankin scale [mRS]) and quality of life (QoL) following treatment with IVIG within 4 to 10 weeks (pre-mRS vs. post-mRS, P < 0.0001; pre-QoL vs. post-QoL, P = 0.0003) and sustained after 5 years of treatment (pre-mRS vs. present mRS, P = 0.0003; pre-QoL vs. present QoL, P = 0.0002). CONCLUSIONS: This article describes one of the largest single-center experiences of 23 patients with SPS and related syndromes and is the first to establish the long-term efficacy of regular IVIG using a patient-reported scoring system (Birmingham Response to Immunomodulatory Therapy [BRIT]). Consistent improvement in QoL and functional scores were seen over nearly 5 years after regular use of IVIG. It is recommended to use BRIT scores to assess the initial response as well as to monitor continued improvement to immunomodulation in SPS.

Multicomponent Informed Consent with Marshallese Participants.

Pacific Islanders are the second fastest-growing population in the United States; however, Pacific Islanders, and Marshallese specifically, are underrepresented in health research. A community-based participatory research (CBPR) approach was used to engage Marshallese stakeholders and build an academic-community research collaborative to conduct health disparities research. Our CBPR partnership pilot tested a multicomponent consent process that provides participants the option to control the use of their data. Consent forms used concise plain language to describe study information, including participant requirements, risks, and personal health information protections, and were available in both English and Marshallese. This study demonstrates that when provided a multicomponent consent, the vast majority of consenting study participants (89.6%) agreed to all additional options, and only five (10.4%) provided consent for some but not all options. Our description of the development and implementation of a multicomponent consent using a CBPR approach adds a specific example of community engagement and may be informative for other indigenous populations.

Enrollee Experience with Providers in the Arkansas Medicaid Expansion Program.

BACKGROUND: Patient ratings of their healthcare experience as a quality measure have become critically important since the implementation of the Affordable Care Act (ACA). The ACA enabled states to expand Medicaid eligibility to reduce uninsurance nationally. Arkansas gained approval to use Medicaid funds to purchase a qualified health plan (QHP) through the ACA marketplace for newly eligible beneficiaries. OBJECTIVE: We compare patient-reported satisfaction between fee-for-service Medicaid and QHP participants. DESIGN: The Consumer Assessment of Healthcare Providers and Systems (CAHPS) was used to identify differences in Medicaid and QHP enrollee healthcare experiences. Data were analyzed using a regression discontinuity design. PARTICIPANTS: Newly eligible Medicaid expansion participants enrolled in Medicaid during 2013 completed the Consumer Assessment of Health Providers and Systems (CAHPS) survey in 2014. Survey data was analyzed for 3156 participants (n = 1759 QHP/1397 Medicaid). MEASURES: Measures included rating of personal and specialist provider, rating of all healthcare received, and whether the provider offered to communicate electronically. Demographic and clinical characteristics of the enrollees were controlled for in the analyses. METHODS: Regression-discontinuity analysis was used to evaluate differential program effects on positive ratings as measured by the CAHPS survey while controlling for demographic and health characteristics of participants. KEY RESULTS: Adjusted logistic regression models for overall healthcare (OR = 0.71, 95%CI = 0.56-0.90, p = 0.004) and personal doctor (OR = 0.68, 95%CI = 0.53-0.87, p = 0.002) predicted greater satisfaction among QHP versus Medicaid participants. Results were not significant for specialists or for use of electronic communication with provider. CONCLUSIONS: Using a quasi-experimental statistical approach, we were able to control for observed and unobserved heterogeneity showing that among participants with similar characteristics, including income, QHP participants rated their personal providers and healthcare higher than those enrolled in Medicaid. Access to care, utilization of care, and healthcare and health insurance literacy may be contributing factors to these results.