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Studies have been carried out to investigate the disposition of nicardipine hydrochloride following intravenous and oral administration to male volunteers. Following oral administration of a radiolabelled dose, nicardipine was shown to be rapidly and extensively metabolised and to be rapidly eliminated from plasma. After intravenous infusion of nicardipine at 5 mg-1 for 3 h, plasma levels declined biexponentially, and clearance values were of the same order as hepatic blood flow. With repeated oral administration, 20 mg three times daily for 28 days, plasma levels rose over the first 3 days of administration and then declined to some extent. Possible reasons for this decline are discussed. Steady-state plasma levels and bioavailability show a nonlinear relationship with doses over the range 10-40 mg three times daily. Food consumption has been shown to reduce the bioavailability of nicardipine when the food is taken before or at the same time as nicardipine administration. [ABSTRACT FROM AUTHOR]

Organic thin films are of great interest due to their intriguing interfacial and functional properties, especially for device applications such as thin-film transistors and sensors. As their thickness approaches single nanometer thickness, characterization and interpretation of the extracted data become increasingly complex. In this study, plasma polymerization is used to construct ultrathin films that range in thickness from 1 to 20 nm, and time-of-flight secondary ion mass spectrometry coupled with principal component analysis is used to investigate the effects of film thickness on the resulting spectra. We demonstrate that for these cross-linked plasma polymers, at these thicknesses, the observed trends are different from those obtained from thicker films with lower degrees of cross-linking: contributions from ambient carbon contamination start to dominate the mass spectrum; cluster-induced nonlinear enhancement in secondary ion yield is no longer observed; extent of fragmentation is higher due to confinement of the primary ion energy; and the size of the primary ion source also affects fragmentation (e.g., Bi 1 versus Bi 5 ). These differences illustrate that care must be taken in choosing the correct primary ion source as well as in interpreting the data., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

Motivated by clinical problems of titanium implant degradation, we developed a workflow that enabled assessment of surface oxide dynamics as a function of clinical interventions and inflammation conditions. We found that mechanical damage led to decrease of stoichiometric TiO 2 ratio in the passivation oxide film and further resulted in accelerated degradation under inflammatory anaerobic conditions. This method can be employed for the assessment of surface oxides to monitor implant safety., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

The one-bone forearm (OBF) is a salvage technique that may be used to correct global forearm instability secondary to osseous defects. This study aims to provide an overview of the contemporary literature regarding the OBF. A literature review was conducted electronically across MEDLINE, Embase, and PubMed databases in May 2020. Studies were eligible for inclusion if published in the English language; detailed the use of the OBF procedure to correct forearm instability; and were original data studies reporting qualitative or quantitative outcomes. Thirty-four studies, describing a cohort of 210 patients undergoing 211 OBFs, were documented in the literature. The primary etiology necessitating the OBF was trauma, followed by genetic/congenital disorders and infections. Technically, the OBF was most frequently achieved via an end-to-end osteosynthesis with plate fixation. In total, 85.0% (154/182) of OBF were fused in neutral rotation or varying degrees of pronation. Union was achieved in more than 80.0% (174/211) of OBFs. The OBF is a feasible salvage technique that has been used for a wide spectrum of pathology, providing satisfactory outcomes in most cases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Research suggests that mental activation of human social support may reduce stress reactivity. However, the extent to which social support from pets elicits a similar effect has been less explored. This study aims to determine whether the mental activation of one's pet dog reduces stress reactivity to a subsequent experimental stressor. In a 2 × 2 design, 132 dog-owning participants (M age = 20.14; 80% female) were randomly assigned to one of two mental activation conditions (pet dog; general) and one of two stressor conditions (social-evaluative; cognitive). Data were analyzed with two-way ANOVAs with self-reported (positive/negative affect, negative self-evaluation) and physiological (blood pressure, heart rate) dependent variables. Results indicated that participants randomized to the pet dog mental activation condition had smaller decreases in positive affect from baseline to post-stressor compared to the general mental activation condition. However, there were no significant interactions between time and mental activation condition on negative affect, negative self-evaluation, heart rate, or blood pressure. Thus, the mental activation of one's pet dog had a minimal effect on stress reactivity to a cognitive or social-evaluative stressor. Results suggest that the physical presence of an animal may be an essential mechanism underlying the benefits of animal-derived social support.

The aim of this research was to determine whether parent/child pairs choosing products from a grocery aisle labeled with front-of-package (FOP) nutrition labels would make more healthful choices than pairs who viewed the same items without labels, and to determine the added value of viewing an explanatory video before choosing. In this experiment, 175 parent/child pairs chose USD 20 worth of packaged foods and beverages from a grocery aisle in a research laboratory and were randomly assigned to see products that either did or did not have 0-4-star FOP labels, with more stars indicating more healthful products. Among those participants with access to FOP labels, half were randomly assigned to view a 30 s video explaining the FOP labels before selecting foods. Participants who saw the explanatory video before selecting among products with FOP labels chose foods with significantly more stars than participants who saw the FOP-labeled products without the video; however, there was no significant difference in mean stars on selected products between the group that saw the videos and the control group that saw neither the video nor FOP labels. We conclude that explaining new FOP labels to consumers may be necessary for the labels to prompt more healthful choices.

Background: Compared to the traditional open carpal tunnel release (OCTR), the additional safety and efficacy benefits of endoscopic carpal tunnel release (ECTR) remains unclear. The aim of this study is to evaluate the outcomes of ECTR versus conventional OCTR as well as determine if a difference exists between the 2 most common endoscopic techniques: the single-portal and the dual-portal endoscopic technique., Methods: We conducted a systematic literature search of Medline, Embase, PubMed, and the CENTRAL. Additional articles were identified by handsearching reference lists. We included all randomized controlled trials that compared outcomes of ECTR with OCTR technique. Outcomes assessed included length of surgery, patient reported symptom and functional measures, time to return to work, and complications. A sub-group analysis was performed to indirectly compare single- versus dual-portal endoscopic approaches. Statistical analysis was performed via a random-effects model using Review Manager 5 Software., Results: A meta-analysis of 23 studies revealed a significantly higher incidence of transient postoperative nerve injury with ECTR, regardless of the number of portals, as compared with OCTR, although overall complication and re-operation rates were equivalent. Scar tenderness was significantly diminished with dual-portal endoscopic release when compared to single-portal and open methods. The rates of pillar pain, symptom relief, and patient reported satisfaction did not differ significantly between treatment groups., Conclusions: Although endoscopic surgery may be appealing in terms of reduced postoperative morbidity and a faster return to work for patients, surgeons should be mindful of the associated learning curve and higher incidence of transient nerve injury. Further study is required to identify if an advantage exists between different endoscopic techniques.

This is the second half of a two-part Tutorial on the basics of the time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis of bio-related samples. Part I of this Tutorial series covers planning for a ToF-SIMS experiment, preparing and shipping samples, and collecting ToF-SIMS data. This Tutorial aims at helping the ToF-SIMS user to process, display, and interpret ToF-SIMS data. ToF-SIMS provides detailed chemical information about surfaces but comes with a steep learning. The purpose of this Tutorial is to provide the reader with a solid foundation in the ToF-SIMS data analysis., (2023 Published under an exclusive license by the AVS.)

Physical activity is known to be one of the most health-beneficial behaviors, and salutogenic design modifications to the built environment can facilitate increased physical activity. Unfortunately, it is not often clear in advance which environmental and urban design implementations will generate increases in activities such as walking, and which will have little impact or even reduce walking. The present study tested the feasibility and acceptability of a virtual reality (VR) model for pre-testing urban designs for their impact on walking. Using a wearable VR head-mounted display/computer, young adults (n = 40) walked freely through a large indoor gymnasium, simultaneously walking through a virtual model of an urban streetscape that was designed to be modifiable and allow for testing impacts on walking of various changes to the urban environment. The majority of participants found the experience to be acceptable: pleasant and nonaversive, and they walked freely through the VR model for approximately 20 min, on average. Using modifiable VR models to pre-test built-environment changes for their impacts on walking behavior appears to be a feasible and acceptable approach and worthy of continued research investigation., (© 2023. The Author(s).)

Decision making in a rapidly changing context, such as the development and progression of a pandemic, requires a dynamic assessment of multiple variable and competing factors. Seemingly beneficial courses of action can rapidly fail to deliver a positive outcome as the context changes. In this paper, we present a flexible data-driven agent-based simulation framework that considers multiple outcome criteria to increase opportunities for safe mobility and economic interactions on urban transit networks while reducing the potential for Covid-19 contagion in a dynamic setting. Using a case study of the Victoria line on the London Underground, we model a number of operational interventions with varied demand levels and social distancing constraints including: alterations to train headways, dwell times, signalling schemes, and train paths. Our model demonstrates that substantial performance gains ranging from 12.3-195.7% can be achieved in metro service provision when comparing the best performing operational scheme and headway with those realised on the Victoria line during the pandemic., (© 2023. The Author(s).)

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is used widely throughout industrial and academic research due to the high information content of the chemically specific data it produces. Modern ToF-SIMS instruments can generate high mass resolution data that can be displayed as spectra and images (2D and 3D). This enables determining the distribution of molecules across and into a surface and provides access to information not obtainable from other methods. With this detailed chemical information comes a steep learning curve in how to properly acquire and interpret the data. This Tutorial is aimed at helping ToF-SIMS users to plan for and collect ToF-SIMS data. The second Tutorial in this series will cover how to process, display, and interpret ToF-SIMS data.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has had a dramatic impact on individual and societal behaviors, as well as on health care systems. It confers a unique opportunity to examine the relationship among disease, policies, and patterns of activity, as well as their impacts on surgical unit functionality. This study aims to compare the distribution and patterns of injury at a tertiary hand surgery trauma center before and during the COVID-19 pandemic., Methods: A retrospective analysis of all patients presenting to the Royal North Shore Hospital hand surgery service in the 5-week period from March 16 to April 21 in 2019 and 2020 was undertaken, forming 2 cohorts for comparison. Demographic, injury, and operative data were collected and compared descriptively using comparative statistics., Results: There were 114 primary operative presentations during the 5-week period in 2020, representing a 27.4% decrease from the 157 presentations during the equivalent period in 2019. There was an increase in the proportion of emergency presentations from 73.9% in 2019 to 85.1% in 2020 ( P = .03), with a corresponding decrease in elective presentations during 2020. The incidence of sporting injuries and motor vehicle accidents decreased in 2020, whereas falls and accidents involving knives and tools remained relatively constant. Operating times decreased in 2020, whereas the length of hospital stay remained constant., Conclusions: The COVID-19 pandemic and consequent restrictions of activity have had substantial impacts on the patterns of hand trauma and its management. These insights have implications for staff and resource management during times of social disruption in the future.

Background: Reverse homodigital island flaps (RHIFs) are increasingly used to reconstruct traumatic fingertip injuries, but there is limited evidence on the efficacy of this technique. We performed a systematic review of the literature to establish the safety and functional outcomes of RHIF for traumatic fingertip injuries., Methods: Electronic searches were performed using 3 databases (PubMed, Ovid Medline, Cochrane CENTRAL) from their date of inception to April 2020. Relevant studies were required to report on complications and functional outcomes for patients undergoing RHIF for primary fingertip reconstruction. Data were extracted from included studies and analyzed., Results: Sixteen studies were included, which produced a total cohort of 459 patients with 495 fingertip injuries. The index and middle fingers were involved most frequently (34.6% and 34.1%, respectively), followed by the ring finger (22%), the little finger (6.7%), and the thumb (2.6%). The mean postoperative static and moving 2-point discrimination was 7.2 and 6.7 mm, respectively. The mean time to return to work was 8.4 weeks. The mean survivorship was 98.4%, with the pooled complication rate being 28%. The pooled complication rate of complete flap necrosis was 3.6%, of partial flap necrosis was 10.3%, of venous congestion was 14.6%, of pain or hypersensitivity was 11.5%, of wound infection was 7.2%, of flexion contractures was 6.3%, and of cold intolerance was 17.7%., Conclusions: Reverse homodigital island flaps can be performed safely with excellent outcomes. To minimize complications, care is taken during dissection and insetting, with extensive rehabilitation adhered to postoperatively. Prospective studies assessing outcomes of RHIF compared with other reconstruction techniques would be beneficial.

Intra-articular fracture dislocations of the base of the middle phalanx are complex and debilitating injuries that present a management conundrum when nonreconstructable. Hemi-hamate arthroplasty (HHA) is a treatment modality of particular use in the setting of highly comminuted fractures. This systematic review aims to summarize the reported outcomes of HHA in this context. A literature search was conducted using MEDLINE, Embase, and PubMed, yielding 22 studies with 235 patients for inclusion. The weighted mean postoperative range of movement at the proximal interphalangeal joint was 74.3° (range, 62.0°-96.0°) and at the distal interphalangeal joint was 57.0° (range, 14.0°-80.4°). The weighted mean postoperative pain Visual Analog Scale was 1.0 (range, 0.0-2.0). The weighted mean postoperative grip strength was 87.1% (range, 74.5%-95.0%) of the strength on the contralateral side. Posttraumatic arthritis was reported in 18% of cases, graft collapse in 4.2%, and donor site morbidity in 3.0%, with a mean follow-up period of 28.4 months (range, 1-87 months). Hemi-hamate arthroplasty is a reliable and effective technique for the reconstruction of intra-articular base of middle phalangeal fracture dislocations, affording symptomatic relief and functional restoration. Further research is required to assess the true incidence of long-term complications.

Proximal interphalangeal joint (PIPJ) arthrodesis is a salvage option in the management of end-stage PIPJ arthropathy. Numerous techniques have been described, including screws, Kirschner wires, tension band wiring, intramedullary devices, and plate fixation. There remains no consensus as to the optimum method, and no recent summary of the literature exists. A literature search was conducted using the MEDLINE, EMBASE, and PubMed databases. English-language articles reporting PIPJ arthrodesis outcomes were included and presented in a systematic review. Pearson χ 2 and 2-sample proportion tests were used to compare fusion time, nonunion rate, and complication rate between arthrodesis techniques. The mean fusion time ranged from 5.1 to 12.9 weeks. There were no statistically significant differences in fusion time between arthrodesis techniques. Nonunion rates ranged from 0.0% to 33.3%. Screw arthrodesis demonstrated a lower nonunion rate than wire fusion (3.0% and 8.5% respectively; P = .01). Complication rates ranged from 0.0% to 22.1%. Aside from nonunions, there were no statistically significant differences in complication rates between arthrodesis techniques. The available PIPJ arthrodesis techniques have similar fusion time, nonunion rate, and complication rate outcomes. The existing data have significant limitations, and further research would be beneficial to elucidate any differences between techniques.

Bennett fractures are inherently unstable partial articular fractures of the base of the first metacarpal, often resulting from an axial load applied to a partially flexed metacarpal. Multiple options are available for the surgical stabilization of Bennett fractures; each option has associated drawbacks. We present a technique of fixation with headless compression screw(s), combined with suspension fixation, to overcome some of these limitations, with good results., (© 2022 The Authors.)

The dynamics of human mobility have been known to play a critical role in the spread of infectious diseases like COVID-19. In this paper, we present a simple compact way to model the transmission of infectious disease through transportation networks using widely available aggregate mobility data in the form of a zone-level origin-destination (OD) travel flow matrix. A key feature of our model is that it not only captures the propagation of infection via direct connections between zones (first-order effects) as in most existing studies but also transmission effects that are due to subsequent interactions in the remainder of the system (higher-order effects). We demonstrate the importance of capturing higher-order effects in a simulation study. We then apply our model to study the first wave of COVID-19 infections in (i) Italy, and, (ii) the New York Tri-State area. We use daily data on mobility between Italian provinces (province-level OD data) and between Tri-State Area counties (county-level OD data), and daily reported caseloads at the same geographical levels. Our empirical results indicate substantial predictive power, particularly during the early stages of the outbreak. Our model forecasts at least 85% of the spatial variation in observed weekly COVID-19 cases. Most importantly, our model delivers crucial metrics to identify target areas for intervention., (© 2022. The Author(s).)

Vascularized joint transfer (VJT) from the proximal interphalangeal joint (PIPJ) of the toe is an attractive reconstructive option in cases of nonsalvageable finger PIPJ but is limited by equivocal functional outcomes. This systematic review aims to provide an update on vascularized toe-to-finger PIPJ transfers, examining functional outcomes, complications, and the latest refinements in operative technique. A systematic review of the available literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies examining vascularized toe-to-finger PIPJ transfer for post-traumatic indications were included for analysis. Outcomes assessed included postoperative active range of motion, extension lag, and complications. Thirteen studies examining 210 VJTs were analyzed. Five VJTs experienced microsurgical failure giving an overall survival rate of 97.6%. Average postoperative PIPJ active range of motion (ROM) was 40.3° ± 12.9°, with an average extensor lag of 29° ± 10.5° and mean flexion of 68.9° ± 10.9°. For studies reporting complication outcomes, 59/162 complications were seen. No significant differences were seen between studies published prior to 2013 and after 2013 when comparing digital ROM ( P = .123), flexion ( P = .602), and extensor lag ( P = .280). Studies using a reconstructive algorithm based on prior assessment of the donor toe central slip and recipient finger anatomy had significantly improved ROM outcomes ( P = .013). Although VJT provides a reliable option for autologous reconstruction in posttraumatic joints, it is limited by impaired postoperative ROM. Careful assessment of the donor toe and recipient finger anatomy followed by systematic and meticulous reconstruction may lead to improved functional outcomes.

Proximal phalangeal fractures have traditionally been fixed via either Kirschner wires or dorsal plating. Concerns regarding lack of compression and potential for infection with wire fixation, and adhesion formation and stiffness with plating, have lead to alternative fixation methods, such as intramedullary screw fixation. However, the literature regarding this modality is limited. Methods: A systematic review was performed to review the literature regarding intramedullary screw fixation for proximal phalangeal fractures. English language studies that reported original data and commented on at least one postoperative measure of function were eligible for inclusion. 4 studies were eligible for inclusion, with a further 3 studies assessing proximal and middle phalanges analysed separately. Total active motion was greater than 240° in all proximal phalangeal studies; mean post-operative DASH was 3.62. 6% of patients sustained a major complication. Intramedullary screw fixation of proximal phalangeal fractures is safe, providing stable fixation to allow early motion.

Objective: To determine whether daylight savings time (DST) transitions have an effect on road traffic casualties in Great Britain using causal regression discontinuity design (RDD) analysis. We undertake aggregate and disaggregate spatial and temporal analyses to test the commonly referenced sleep and light hypotheses., Design: The study takes the form of a natural experiment in which the DST transitions are interventions to be evaluated. Two outcomes are tested: (1) the total number of casualties of all severities and (2) the number of fatalities., Data: Data were obtained from the UK Department for Transport STATS19 database. Over a period of 14 years between 2005 and 2018, 311 766 total casualties and 5429 fatalities occurred 3 weeks on either side of the Spring DST transition and 367 291 total casualties and 6650 fatalities occurred 3 weeks on either side of the Autumn DST transition., Primary Outcome Measure: An RDD method was applied. The presence of a causal effect was determined via the degree of statistical significance and the magnitude of the average treatment effect., Results: All significant average treatment effects are negative (54 significant models out of 287 estimated), indicating that there are fewer casualties following the transitions. Overall, bootstrapped summary statistics indicate a reduction of 0.75 in the number of fatalities (95% CI -1.61 to -0.04) and a reduction of 4.73 in the number of total casualties (95% CI -6.08 to -3.27) on average per year at both the Spring and Autumn DST transitions combined., Conclusions: The results indicate minor reductions in the number of fatalities following the DST transitions, and thus, our analysis does not support the most recent UK parliamentary estimate that there would be 30 fewer fatalities in Great Britain if DST was to be abolished. Furthermore, the results do not provide conclusive support for either the sleep or light hypotheses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Metal-on-metal disease (MOMD) is a rare condition following arthroplasty and has predominantly been reported following hip and knee replacement. Isolated case reports exist with respect to MOMD following total wrist arthroplasty-however, the literature remains limited. Here, we present the history and radiographic and histopathologic features of such a case, and summarize the literature and provide management recommendations.

Physical activity (PA) benefits health, and intensive environmental modifications can increase children's PA. Research has not yet addressed if subtle environmental cues, such as posters depicting PA, increase child PA. In the current study, it was hypothesized that children exposed to active posters (vs. nature posters) would spend a larger proportion of free play time engaging with active toys (relative to sedentary toys). Participants were randomly assigned to one of two conditions in which posters on a laboratory wall depicted 1. People being active, or 2. Nature scenes. Children aged 5-10 years (N = 175) could play with up to eight toys (four active, four sedentary) while parents completed study-related surveys. The proportion of playtime that was active was compared between groups. Poster type did not have a significant effect on proportion of active playtime. Previous environmental interventions that increase children's PA have done so through enhancing access to active opportunities, rather than via signage. It is possible that poster interventions such as this may not influence children's PA, or perhaps other types of cues would have been more effective. Future research should investigate subtle environmental cues that match both the target audience and the accessible PA options (e.g., posters depicting children playing with available active toys) and explore other low-investment environmental modifications to boost children's PA.

Background: There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19., Objective: To determine if ACEIs and ARBs are associated with an increased risk of Covid-19 hospitalization overall, or hospitalization involving intensive care unit (ICU) admission, invasive mechanical ventilation, or death., Design: Observational case-control study., Participants: Medicare beneficiaries aged ≥ 66 years with hypertension, treated with ACEIs, ARBs, calcium channel blockers (CCBs), or thiazide diuretics., Main Measures: Adjusted odds ratios (OR) and 95% confidence intervals (CI) for the outcomes of Covid-19 hospitalization, or hospitalization involving ICU admission, invasive mechanical ventilation, or death., Results: A total of 35,300 cases of hospitalized Covid-19 were matched to 228,228 controls on calendar date and neighborhood of residence. The median age of cases was 79 years, 57.4% were female, and the median duration of hospitalization was 8 days (interquartile range 5-12). ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97). Similar results were obtained for hospitalizations involving ICU admission, invasive mechanical ventilation, or death. There were no meaningful differences in risk for ACEIs compared with ARBs. In an analysis restricted to monotherapy with a first-line agent, CCBs were associated with a small increased risk of Covid-19 hospitalization compared with ACEIs (OR 1.09, 95% CI 1.04-1.14), ARBs (OR 1.10, 95% CI 1.05-1.15), or thiazide diuretics (OR 1.11, 95% CI 1.03-1.19)., Conclusions: ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death. The finding of a small increased risk of Covid-19 hospitalization with CCBs was unexpected and could be due to residual confounding., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Drug delivery to the brain is limited by poor penetration of pharmaceutical agents across the blood-brain barrier (BBB), within the brain parenchyma, and into specific cells of interest. Nanotechnology can overcome these barriers, but its ability to do so is dependent on nanoparticle physicochemical properties including surface chemistry. Surface chemistry can be determined by a number of factors, including by the presence of stabilizing surfactant molecules introduced during the formulation process. Nanoparticles coated with poloxamer 188 (F68), poloxamer 407 (F127), and polysorbate 80 (P80) have demonstrated uptake in BBB endothelial cells and enhanced accumulation within the brain. However, the impact of surfactants on nanoparticle fate, and specifically on brain extracellular diffusion or intracellular targeting, must be better understood to design nanotherapeutics to efficiently overcome drug delivery barriers in the brain. Here, we evaluated the effect of the biocompatible and commonly used surfactants cholic acid (CHA), F68, F127, P80, and poly (vinyl alcohol) (PVA) on poly (lactic-co-glycolic acid)-poly (ethylene glycol) (PLGA-PEG) nanoparticle transport to and within the brain. The inclusion of these surfactant molecules decreases diffusive ability through brain tissue, reflecting the surfactant's role in encouraging cellular interaction at short length and time scales. After in vivo administration, PLGA-PEG/P80 nanoparticles demonstrated enhanced penetration across the BBB and subsequent internalization within neurons and microglia. Surfactants incorporated into the formulation of PLGA-PEG nanoparticles therefore represent an important design parameter for controlling nanoparticle fate within the brain., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This paper quantifies behavioural responses to changes in the jurisdiction of a congestion charge, with a successive focus on (i) an extension and (ii) a reduction in the size of the charging zone. We exploit the unanticipated nature of both the implementation and removal of London's Western Expansion Zone (WEZ) as quasi-natural experiments to test whether individual responses to policies are asymmetric. We use the UK Department of Transport Annual Average Daily Flow (AADF) data, which records traffic flows for seven transport modes (including cars, buses, bicycles, heavy and light goods vehicles). Using a difference-in-differences approach, we find that the introduction of the WEZ led to a 4.9% decline in road traffic flows in the new congestion charge area. These results are robust to different model specifications. HGVs traffic did not significantly change post-WEZ, which indicates that their road demand is price inelastic. The removal of the WEZ led to no significant variations in traffic. This result indicates asymmetry in behaviour with persistent changes in post-intervention traffic demand levels., Competing Interests: The authors have declared that no competing interests exist.

Physical inactivity remains a global epidemic leading to an estimated 5 million preventable deaths per year. Although there exist numerous public-health campaigns aimed at increasing physical activity (PA), a potentially fruitful but underexplored avenue to promote both human and animal health is veterinary-prescribed PA programs. The aim of this study was to determine the feasibility and acceptability of incorporating veterinary-prescribed PA programming into a diverse array of clinic settings. Participants (n = 722 veterinary-clinic staff (VS); n = 1028 dog owners (DOs)) completed an online survey assessing: (a) the perceived importance of PA for promoting health and preventing disease, (b) willingness to participate in a veterinary-prescribed PA program, and (c) potential benefits and barriers of such a program. Both groups of participants indicated that PA is important for both human and animal health (97% and 98% of VS and 92% and 93% of DOs said PA is very or extremely important for animal and human health, respectively). Additionally, most participants in both groups expressed an interest in participating in a veterinary-prescribed PA program in the future, with only 11% of DOs and 10% of VS saying they were not interested. Benefits and barriers of this type of intervention for both practitioners and patients were also identified. Incorporating veterinary-prescribed PA programming into veterinary clinics seems to be acceptable to both DOs and VS. Additionally, many VS believe such programming would be feasible at their clinics; thus, pursuing such programs appears to be a promising avenue for promoting human and animal health.

US Public Law 114-216 dictates that food producers in the United States of America will be required to label foods containing genetically modified organisms (GMOs) starting in 2022; however, there is little empirical evidence demonstrating how U.S. consumers would use food labels that indicate the presence or absence of GMOs. The aim of this two-phase study was to determine how attitudes towards GMOs relate to food choices and how labels indicating the presence or absence of GMOs differentially impact choices among college students-the age group which values transparent food labeling more than any other. Participants ( n = 434) made yes/no choices for each of 64 foods. In both phases of the study, participants were randomly assigned to seeing GMO Free labels, contains GMOs labels, or no GMO labels. Across the two phases, 85% of participants reported believing that GMOs were at least somewhat dangerous to health (42% believed GMOs to be dangerous), yet in both studies, although eye-tracking data verified that participants attended to the GMO labels, these labels did not significantly affect food choices. Although college consumers may believe GMOs to be dangerous, their food choices do not reflect this belief.

Introduction: Speed cameras have been implemented to improve road safety over recent decades in the UK. Although the safety impacts of the speed camera have been estimated thoroughly, the criteria for selecting camera sites have rarely been studied. This paper evaluates the current speed camera sites selection criteria in the UK based on safety performance., Method: A total of 332 speed cameras and 2,513 control sites with road traffic accident data are observed from 2002 to 2010. Propensity score matching method and empirical Bayes method are employed and compared to estimate the safety effects of speed cameras under different scenarios., Results: First, the main characteristics of speed cameras meeting and not meeting the selection criteria are identified. The results indicate that the proximity to school zones and residential neighborhoods, as well as population density, are the main considerations when selecting speed camera sites. Then the official criteria used for selecting camera sites are evaluated, including site length (a stretch of road that has a fixed speed camera or has had one in the past), previous accident history, and risk value (a numerical scale of the risk level). The results suggest that a site length of 500 m should be used to achieve the optimum safety effects of speed cameras. Furthermore, speed cameras are most effective in reducing crashes when the requirement of minimum number of historical killed and seriously injured collisions (KSIs) is met. In terms of the risk value, it is found that the speed cameras can obtain optimal effectiveness with a risk value greater than or equal to 30, rather than the recommended risk value of 22., (Copyright © 2020 National Safety Council and Elsevier Ltd. All rights reserved.)

Background: Regular physical activity (PA) promotes health and can prevent and treat diseases among both humans and dogs. Unfortunately, most U.S. adults do not meet PA recommendations, and many dogs are also insufficiently active. Veterinary-prescribed PA programs have shown some success in increasing activity among overweight dogs, but the impacts of such programs have not yet been tested for efficacy among otherwise-healthy dogs and owners. In addition, although wearable devices that monitor PA and provide individuals with feedback (e.g., progress toward a daily step goal) can effectively increase human PA, it is unclear what impact similar wearable devices have on human and dog PA when the PA-monitoring devices are worn by dogs. The present study assessed the impact of an 8-week veterinary-prescribed PA program on activity and health among dogs and their owners, and randomized participants (n = 59) to two groups: one in which PA was measured but not visible to participants (n = 30), and one in which PA was measured and real time feedback was visible through a wearable device (n = 29)., Results: Participants in both groups showed significant PA increases over the course of the 8-week program. Biomedical testing performed at the veterinary clinic facilitated early diagnosis of systemic illness in one human participant. The frequency of hypertension in human participants decreased significantly from baseline to the end of the program (week 8). Other health indices (e.g., BMI in humans, body weight and BCS in dogs) improved, albeit not to a statistically significant extent, over the course of the program. There were no significant differences on the outcomes of interest between the two experimental conditions., Conclusions: Veterinary-prescribed PA programs appear promising for increasing PA among insufficiently active but otherwise healthy dogs as well as their owners. Additional testing of veterinary-prescribed PA is warranted, particularly at other types of veterinary clinics (e.g., private practices). Incorporating wearable devices permitting owners to track canine PA did not appear necessary for obtaining these benefits; however, additional studies investigating alternative devices or different time periods may be warranted.

Background: A previous FDA study reported a favorable benefit risk for apixaban compared with warfarin for stroke prevention in older non-valvular atrial fibrillation (NVAF) patients (≥ 65 years). However, it remains unclear whether this favorable benefit risk persists in other populations including younger users. We examined if a similar benefit risk was observed in the Sentinel System and if it varied by age group., Objective: To examine the risk of ischemic stroke, gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH) in apixaban users compared with warfarin users in Sentinel Distributed Database (SDD)., Design and Participants: A retrospective new user cohort study was conducted among patients, 21 years and older initiating apixaban and warfarin for NVAF, between December 28, 2012, and June 30, 2018, in the SDD., Main Measures: Cox proportional hazard regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for each outcome (ischemic stroke, GI bleeding, and ICH) in propensity score matched apixaban users compared with the warfarin users. Subgroup analyses by age (21-64, 65-74, and 75+ years) were conducted., Key Results: After matching, 55.3% and 58.4% (n = 55,038) of the apixaban and warfarin users were included in the main analysis. GI bleeding was the most common outcome. The HR (95% CI) for GI bleeding, ICH, and ischemic stroke in apixaban users compared with warfarin users were 0.57 (0.50-0.66), 0.53 (0.40-0.70), and 0.56 (0.45-0.71) respectively. The reduced risk of these outcomes in apixaban compared with warfarin users persisted across age groups., Conclusion: In NVAF patients of all ages initiating either apixaban or warfarin for stroke prevention in the Sentinel System, apixaban was associated with a decreased risk of GI bleeding, ICH, and ischemic stroke compared with warfarin. Among patients less than 65 years of age, apixaban use was associated with a decreased risk of GI bleeding and ischemic stroke.

Background: Patients with atrial fibrillation and severely decreased kidney function were excluded from the pivotal non-vitamin K antagonist oral anticoagulants (NOAC) trials, thereby raising questions about comparative safety and effectiveness in patients with reduced kidney function. The study aimed to compare oral anticoagulants across the range of kidney function in patients with atrial fibrillation., Methods and Results: Using a US administrative claims database with linked laboratory data, 34 569 new users of oral anticoagulants with atrial fibrillation and estimated glomerular filtration rate ≥15 mL/(min·1.73 m 2 ) were identified between October 1, 2010 to November 29, 2017. The proportion of patients using NOACs declined with decreasing kidney function-73.5%, 69.6%, 65.4%, 59.5%, and 45.0% of the patients were prescribed a NOAC in estimated glomerular filtration rate ≥90, 60 to 90, 45 to 60, 30 to 45, 15 to 30 mL/min per 1.73 m 2 groups, respectively. Stabilized inverse probability of treatment weighting was used to balance 4 treatment groups (apixaban, dabigatran, rivaroxaban, and warfarin) on 66 baseline characteristics. In comparison to warfarin, apixaban was associated with a lower risk of stroke (hazard ratio [HR], 0.57 [0.43-0.75]; P <0.001), major bleeding (HR, 0.51 [0.44-0.61]; P <0.001), and mortality (HR, 0.68 [0.56-0.83]; P <0.001); dabigatran was associated with a similar risk of stroke but a lower risk of major bleeding (HR, 0.57 [0.43-0.75]; P <0.001) and mortality (HR, 0.68 [0.48-0.98]; P =0.04); rivaroxaban was associated with a lower risk of stroke (HR, 0.69 [0.51-0.94]; P =0.02), major bleeding (HR, 0.84 [0.72-0.99]; P =0.04), and mortality (HR, 0.73 [0.58-0.91]; P =0.006). There was no significant interaction between treatment and estimated glomerular filtration rate categories for any outcome. When comparing one NOAC to another NOAC, there was no significant difference in mortality, but some differences existed for stroke or major bleeding. No relationship between treatments and falsification end points was found, suggesting no evidence for substantial residual confounding., Conclusions: Relative to warfarin, NOACs are used less frequently as kidney function declines. However, NOACs appears to have similar or better comparative effectiveness and safety across the range of kidney function.

Importance: Whether the use of generic vs brand levothyroxine affects thyrotropin levels remains unclear., Objective: To compare the effectiveness of generic vs brand levothyroxine in achieving and maintaining normal thyrotropin levels among new users., Design, Setting, and Participants: This retrospective, 1:1 propensity score-matched longitudinal cohort study used the OptumLabs Data Warehouse administrative claims database linked to laboratory results from commercially insured and Medicare Advantage enrollees throughout the United States. Eligible patients were adults (aged ≥18 years) with thyrotropin levels ranging from 4.5 to 19.9 mIU/L who initiated use of generic or brand-name levothyroxine from January 1, 2008, to October 1, 2017. Data were analyzed from August 13, 2018, to October 25, 2019., Exposure: Patients received generic or brand-name levothyroxine., Main Outcomes and Measures: Proportion of patients with normal vs markedly abnormal thyrotropin levels (<0.1 or >10 mIU/L) within 3 months and with stable thyrotropin levels within 3 months after the thyrotropin value fell into the normal range., Results: A total of 17 598 patients were included (69.0% female; 74.0% White; mean [SD] age, 55.1 [16.0] years), of whom 15 299 filled generic and 2299 filled brand-name levothyroxine prescriptions during the study period. Among 4570 propensity score-matched patients (mean [SD] age, 50.3 [13.8] years; 3457 [75.6%] female; 3510 [76.8%] White), the proportion with normal thyrotropin levels within 3 months of filling levothyroxine prescriptions was similar for patients who received generic vs brand-name levothyroxine (1722 [75.4%; 95% CI, 71.9%-79.0%] vs 1757 [76.9%; 95% CI, 73.4%-80.6%]; P = .23), as was the proportion with markedly abnormal levels (94 [4.1%; 95% CI, 3.4%-5.0%] vs 88 [3.9%; 95% CI, 3.1%-4.7%]; P = .65). Among 1034 propensity score-matched patients who achieved a normal thyrotropin value within 3 months of initiation of levothyroxine, the proportion maintaining subsequent normal thyrotropin levels during the next 3 months was similar for patients receiving generic vs brand-name levothyroxine (427 [82.6%] vs 433 [83.8%]; P = .62)., Conclusions and Relevance: Initiation of generic vs brand-name levothyroxine formulations was associated with similar rates of normal and stable thyrotropin levels. These results suggest that generic levothyroxine as initial therapy for mild thyroid dysfunction is as effective as brand-name levothyroxine.

Background: Giant cell tumors (GCTs) of the distal ulna are rare. Despite being benign, they can be locally aggressive and may recur following conventional treatment by curettage and bone grafting. Salvage reconstructive options after failed conventional treatment include Darrach resection, Suave-Kapandji procedure, hemi-arthroplasty, or total joint arthroplasty. Methods: We discuss reconstruction options for the distal radio-ulnar joint following tumor resection, and present the outcomes of a constrained distal radio-ulnar prosthesis in a 29-year-old male following resection of a distal ulna GCT. Results: Reconstruction of the distal radio-ulnar joint by a constrained prothesis yielded excellent functional outcomes following resection of a GCT of the distal ulna. Conclusions: This case demonstrates that successful oncologic and functional outcomes can be achieved by radical resection of a recurrent GCT of the distal ulna and reconstruction with a constrained total joint arthroplasty.

Objective: To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes., Research Design and Methods: This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388) from September 2006 to September 2015, with follow-up through May 2017. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for incidence of breast cancer according to ever use, cumulative duration of use, cumulative dose of insulin, length of follow-up time, and a combination of dose and length of follow-up time., Results: Ever use of glargine was not associated with an increased risk of breast cancer compared with NPH (HR 0.97; 95% CI 0.88-1.06) or detemir (HR 0.98; 95% CI 0.92-1.05). No increased risk was seen with glargine use compared with either NPH or detemir by duration of insulin use, length of follow-up, or cumulative dose of insulin. No increased risk of breast cancer was observed in medium- or high-dose glargine users compared with low-dose users., Conclusions: Overall, glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir in female Medicare beneficiaries., (© 2020 by the American Diabetes Association.)

This paper quantifies the effect of speed cameras on road traffic collisions using an approximate Bayesian doubly-robust (DR) causal inference estimation method. Previous empirical work on this topic, which shows a diverse range of estimated effects, is based largely on outcome regression (OR) models using the Empirical Bayes approach or on simple before and after comparisons. Issues of causality and confounding have received little formal attention. A causal DR approach combines propensity score (PS) and OR models to give an average treatment effect (ATE) estimator that is consistent and asymptotically normal under correct specification of either of the two component models. We develop this approach within a novel approximate Bayesian framework to derive posterior predictive distributions for the ATE of speed cameras on road traffic collisions. Our results for England indicate significant reductions in the number of collisions at speed cameras sites (mean ATE = -15%). Our proposed method offers a promising approach for evaluation of transport safety interventions., Competing Interests: The authors have declared that no competing interests exist.