Parkinson's Pals: A Student-Led Program to Facilitate Intergenerational Connections and Promote Psychosocial Well-Being Among Persons with Parkinson's Disease.

Parkinson's disease (PD) causes unique motor and non-motor symptoms. Despite symptomatic treatment with pharmacotherapies, many persons with PD report feelings of loneliness and demoralization as their disease progresses. These symptoms greatly interfere with quality of life, necessitating novel treatment strategies. In this report, we introduce a new student-led program to improve psychosocial well-being among persons with PD by pairing them with college students. Through weekly one-on-one meetings, students gain a deeper understanding of PD, while patients gain a new social outlet and purpose. Based on the program's initial successes, we advocate for the adoption of similar programs at universities worldwide.

A global horizon scan for urban evolutionary ecology.

Research on the evolutionary ecology of urban areas reveals how human-induced evolutionary changes affect biodiversity and essential ecosystem services. In a rapidly urbanizing world imposing many selective pressures, a time-sensitive goal is to identify the emergent issues and research priorities that affect the ecology and evolution of species within cities. Here, we report the results of a horizon scan of research questions in urban evolutionary ecology submitted by 100 interdisciplinary scholars. We identified 30 top questions organized into six themes that highlight priorities for future research. These research questions will require methodological advances and interdisciplinary collaborations, with continued revision as the field of urban evolutionary ecology expands with the rapid growth of cities.

Something new and something blue: Responses to novelty in a rodent model of depression and epilepsy comorbidity.

A bidirectional comorbidity exists between depression and epilepsy such that patients with epilepsy are at higher risk for developing depression, and vice versa. Each of these conditions individually can be complicated by behavioral effects that worsen quality of life, but less is known about these interactions within the comorbidity of depression and epilepsy. The SwLo rat has been selectively bred for depression-relevant behaviors and exhibits enhanced limbic seizure susceptibility. This study sought to characterize the effects of novelty and stress on the SwLo rodent model of this comorbidity. It was hypothesized that SwLo rats would exhibit altered responses to novelty, reflected in hyperactivity-, anxiety-, sensation seeking-, and/or compulsive behaviors, and that this would be exacerbated with stress. Compared to the SwHi rat (their depression- and epilepsy-resistant counterparts), SwLo rats showed increased entries in all areas of the Open Field Test and spent significantly more time in the light compartment of the Light-Dark Box. SwLo rats also had a significantly higher number of rearing behaviors in the inner squares of the Open Field Test, the closed arms of the Elevated Plus Maze, and both areas of the Light-Dark Box. They demonstrated increased Nestlet shredding but showed no difference in a marble burying task or in latency to consume food in a novelty suppressed feeding task. Interestingly, restraint stress showed little effect on these behaviors, despite increasing corticosterone levels. Combined, these results suggest an increase in exploratory sensation seeking and hypervigilant information-gathering behaviors in the SwLo rat that are not dependent on corticosterone levels. This shows the utility of this model for studying behavioral effects of comorbid depression and epilepsy and allows for their use in identifying underlying mechanisms or screening treatment strategies for this complex comorbidity.

Immersive Virtual Reality for the Cognitive Rehabilitation of Stroke Survivors.

We present the results of a double-blind phase 2b randomized control trial that used a custom built virtual reality environment for the cognitive rehabilitation of stroke survivors. A stroke causes damage to the brain and problem solving, memory and task sequencing are commonly affected. The brain can recover to some extent, however, and stroke patients have to relearn how to carry out activities of daily living. We have created an application called VIRTUE to enable such activities to be practiced using immersive virtual reality. Gamification techniques enhance the motivation of patients such as by making the level of difficulty of a task increase over time. The design and implementation of VIRTUE is described together with the results of the trial conducted within the Stroke Unit of a large hospital. We report on the safety and acceptability of VIRTUE. We have also observed particular benefits of VR treatment for stroke survivors that experienced more severe cognitive impairment, and an encouraging reduction in time spent in the hospital for all patients that received the VR treatment.

Darker deals? Male dark tetrad preferences for female sex worker services.

The present study explored links between male Dark Tetrad personality traits (psychopathy, Machiavellianism, narcissism, sadism) and preferences for using outdoor and indoor female sex worker services. We also investigated the mediating effects of perceiving sex workers as deviant and as victims. Heterosexual males (N = 347) were recruited to take part in an online survey investigating personality and attitudes towards female sex workers. Path analyses revealed that psychopathy and sadism positively predicted preferences for outdoor but not indoor female sex services. Sex worker choice mediated positive links between narcissism and outdoor female sex worker preferences. Compared to indoor, outdoor sex services are associated with increased aggression and violence. Our findings highlight the importance of considering narcissism and particularly psychopathy and sadism when investigating individual male preferences for outdoor sex services that are being offered by particularly vulnerable women.

It's a conspiracy: Covid-19 conspiracies link to psychopathy, Machiavellianism and collective narcissism.

A proliferation of conspiracy theories has emerged during the Covid-19 health pandemic. The present study investigated individual susceptibility to conspiracy beliefs and the mediating role of Covid related conspiracy beliefs on links between personality and intentional dissemination of Covid-19 conspiracies and willingness to obtain a Covid-19 vaccine. Specifically, we focused on trait psychopathy, Machiavellianism and collective narcissism, as these traits have previously been linked to heightened conspiracy mentalities. We recruited 406 UK participants to take part in an online survey investigating personality and Covid-19 information. Machiavellianism and primary psychopathy positively predicted general and Covid specific conspiracy beliefs, whereas collective narcissism positively predicted Covid specific conspiracy beliefs only. Covid-19 conspiracy beliefs mediated the negative relationships between all traits and willingness to obtain a future vaccine. We discuss possible implications of these findings and provide direction for future research.

Trauma, Power, and Intimate Relationships Among Women in Prison.

The present study, which included four focus groups of women (n = 21) in four New England prisons, aimed to understand how power impacted women's relationships, exposure to violence, and health. Women described power in three ways: (a) power as control over their sexuality and their sexual partners, (b) power emerging from emotional strength, and (c) power referring to a process of empowerment. Women's perceptions and experiences of power were informed by their trauma histories and influenced their sexual behavior and health. Our findings provide a framework for considering incarcerated women's experiences of power in trauma-informed interventions for this marginalized population.

Early Tooth Loss in Children: A Warning Sign of Childhood Hypophosphatasia.

Premature exfoliation of primary teeth may be the first manifestation of this serious condition and the general dental practitioner plays an important role in recognizing dental anomalies and referring patients at an appropriate time. This is imperative to ensuring early diagnosis and good quality patient care. This article describes the case of a 4-year-old boy affected by childhood hypophosphatasia, who presented with premature exfoliation of his primary teeth as the first manifestation of this condition. An overview of the condition is outlined including a discussion of the likelihood of permanent dentition involvement. Clinical relevance: Oral manifestations of hypophosphatasia may be the first and the only signs of this condition and may be the basis upon which a diagnosis is made.

Neisserial Molecular Adaptations to the Nasopharyngeal Niche.

The exclusive reservoir of the genus Neisseria is the human. Of the broad range of species that comprise the Neisseria, only two are frequently pathogenic, and only one of those is a resident of the nasopharynx. Although Neisseria meningitidis can cause severe disease if it invades the bloodstream, the vast majority of interactions between humans and Neisseria are benign, with the bacteria inhabiting its mucosal niche as a non-invasive commensal. Understandably, with the exception of Neisseria gonorrhoeae, which preferentially colonises the urogenital tract, the neisseriae are extremely well adapted to survival in the human nasopharynx, their sole biological niche. The purpose of this review is to provide an overview of the molecular mechanisms evolved by Neisseria to facilitate colonisation and survival within the nasopharynx, focussing on N. meningitidis. The organism has adapted to survive in aerosolised transmission and to attach to mucosal surfaces. It then has to replicate in a nutrition-poor environment and resist immune and competitive pressure within a polymicrobial complex. Temperature and relative gas concentrations (nitric oxide and oxygen) are likely to be potent initial signals of arrival within the nasopharyngeal environment, and this review will focus on how N. meningitidis responds to these to increase the likelihood of its survival.

What Makes Green Cities Unique? Examining the Economic and Political Characteristics of the Grey-to-Green Continuum.

In the United States, urbanization processes have resulted in a large variety-or "continuum"-of urban landscapes. One entry point for understanding the variety of landscape characteristics associated with different forms of urbanization is through a characterization of vegetative (green) land covers. Green land covers-i.e., lawns, parks, forests-have been shown to have a variety of both positive and negative impacts on human and environmental outcomes-ranging from increasing property values, to mitigating urban heat islands, to increasing water use for outdoor watering purposes. While considerable research has examined the variation of vegetation distribution within cities and related social and economic drivers, we know very little about whether or how the economic characteristics and policy priorities of green cities differ from those of "grey" cities-those with little green land cover. To address this gap, this paper seeks to answer the question how do the economic characteristics and policy priorities of green and grey cities differ in the United States? To answer this question, MODIS data from 2001 to 2006 are used to characterize 373 US cities in terms of their vegetative greenness. Information from the International City/County Management Association's (ICMA) 2010 Local Government Sustainability Survey and 2009 Economic Development Survey are used to identify key governance strategies and policies that may differentiate green from grey cities. Two approaches for data analysis-ANOVA and decision tree analysis-are used to identify the most important characteristics for separating each category of city. The results indicate that grey cities tend to place a high priority on economic initiatives, while green cities place an emphasis on social justice, land conservation, and quality of life initiatives.

Preparing individual patient data from clinical trials for sharing: the GlaxoSmithKline approach.

In May 2013, GlaxoSmithKline (980 Great West Road, Brentford, Middlesex, TW8 9GS, UK) established a new online system to enable scientific researchers to request access to anonymised patient level clinical trial data. Providing access to individual patient data collected in clinical trials enables conduct of further research that may help advance medical science or improve patient care. In turn, this helps ensure that the data provided by research participants are used to maximum effect in the creation of new knowledge and understanding. However, when providing access to individual patient data, maintaining the privacy and confidentiality of research participants is critical. This article describes the approach we have taken to prepare data for sharing with other researchers in a way that minimises risk with respect to the privacy and confidentiality of research participants, ensures compliance with current data privacy legal requirements and yet retains utility of the anonymised datasets for research purposes. We recognise that there are different possible approaches and that broad consensus is needed.

Discovery of a rapidly metabolized, long-acting ß(2) adrenergic receptor agonist with a short onset time incorporating a sulfone group suitable for once-daily dosing.

A series of novel, potent, and selective human ß2 adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no ß2 activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.

The statistician's role in the prevention of missing data.

Considerable statistical research has been performed in recent years to develop sophisticated statistical methods for handling missing data and dropouts in the analysis of clinical trial data. However, if statisticians and other study team members proactively set out at the trial initiation stage to assess the impact of missing data and investigate ways to reduce dropouts, there is considerable potential to improve the clarity and quality of trial results and also increase efficiency. This paper presents a Human Immunodeficiency Virus (HIV) case study where statisticians led a project to reduce dropouts. The first step was to perform a pooled analysis of past HIV trials investigating which patient subgroups are more likely to drop out. The second step was to educate internal and external trial staff at all levels about the patient types more likely to dropout, and the impact this has on data quality and sample sizes required. The final step was to work collaboratively with clinical trial teams to create proactive plans regarding focused retention efforts, identifying ways to increase retention particularly in patients most at risk. It is acknowledged that identifying the specific impact of new patient retention efforts/tools is difficult because patient retention can be influenced by overall study design, investigational product tolerability profile, current standard of care and treatment access for the disease under study, which may vary over time. However, the implementation of new retention strategies and efforts within clinical trial teams attests to the influence of the analyses described in this case study.

Statistical resource needs to be increased in the European regulatory agencies.

The following viewpoint from PSI and EFSPI regarding the current level of statistical resource in the European regulatory agencies was first presented as a position paper to a meeting of the EU Heads of Agencies in July 2009, and was endorsed by EFPIA.

Smoking behaviours, access to cigarettes and relationships with alcohol in 15- and 16-year-old schoolchildren.

BACKGROUND: Adolescent smoking is a significant public health concern in the UK and across Europe. This study examines smoking behaviours, methods of accessing cigarettes and use of non-commercial (fake, foreign and single) cigarettes across a sample of schoolchildren. Relationships with alcohol consumption, deprivation, personal income and extra-curricular activities are also explored. METHODS: A cross-sectional survey of 9833 15- and 16-year-old schoolchildren in the North West of England. RESULTS: Cigarettes were most commonly accessed from off-licences and newsagents, but pupils also reported non-commercial access through friends, family and street sellers/neighbours. A high percentage of smokers had bought foreign (57%), fake (28%) and single (54%) cigarettes. Frequent binge drinking, not participating in extra-curricular activities, receiving greater personal income, and having parents that smoked were significantly associated with being a regular and heavier smoker. Frequent binge drinking was also significantly associated with buying foreign/fake or single cigarettes. A higher percentage of those living in deprived areas were current smokers, although deprivation was not an independent predictor of cigarette use. CONCLUSION: Strategies that restrict commercial access to cigarettes among adolescents may increase their reliance on social methods of access, and use of fake, foreign and single cigarettes. Interventions to reduce adolescent smoking must recognize the critical role of parents and communities in discouraging smoking and preventing social access to cigarettes in children. A joint approach to prevention is required that targets children at risk of smoking, heavy alcohol use and associated health-damaging behaviours.

Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study.

BACKGROUND: Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles. METHODS: In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir-emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis. RESULTS: A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, -1.9%; tenofovir-emtricitabine group, -3.6%; P < .001) and lumbar spine (abacavir-lamivudine group, -1.6%; tenofovir-emtricitabine group, -2.4%; P = .036). BMD loss of >or=6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of >or=6% in the hip; 15% vs 5% had a loss of >or=6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofovir-emtricitabine group, +11.92 mg/L; P < .001). CONCLUSIONS: This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.

Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking) and dynamic weight bearing (gait) changes are not measures of neuropathic pain in mice.

BACKGROUND: Spontaneous (non-evoked) pain is a major clinical symptom of neuropathic syndromes, one that is understudied in basic pain research for practical reasons and because of a lack of consensus over precisely which behaviors reflect spontaneous pain in laboratory animals. It is commonly asserted that rodents experiencing pain in a hind limb exhibit hypolocomotion and decreased rearing, engage in both reflexive and organized limb directed behaviors, and avoid supporting their body weight on the affected side. Furthermore, it is assumed that the extent of these positive or negative behaviors can be used as a dependent measure of spontaneous chronic pain severity in such animals. In the present study, we tested these assumptions via blinded, systematic observation of digital video of mice with nerve injuries (chronic constriction or spared nerve injury), and automated assessment of locomotor behavior using photocell detection and dynamic weight bearing (i.e., gait) using the CatWalk system. RESULTS: We found no deficits in locomotor activity or rearing associated with neuropathic injury. The frequency of asymmetric (ipsilaterally directed) behaviors were too rare to be seriously considered as representing spontaneous pain, and in any case did not statistically exceed what was blindly observed on the contralateral hind paw and in control (sham operated and unoperated) mice. Changes in dynamic weight bearing, on the other hand, were robust and ipsilateral after spared nerve injury (but not chronic constriction injury). However, we observed timing, pharmacological, and genetic dissociation of mechanical allodynia and gait alterations. CONCLUSIONS: We conclude that spontaneous neuropathic pain in mice cannot be assessed using any of these measures, and thus caution is warranted in making such assertions.