Miracle-dz/UniFAR-FTUs huggingface dataset:
RRApp, a robust randomization app, for clinical and translational research

While junior clinical researchers at academic medical institutions across the US often desire to be actively engaged in randomized-clinical trials, they often lack adequate resources and research capacity to design and implement them. This insufficiency hinders their ability to generate a rigorous randomization scheme to minimize selection bias and yield comparable groups. Moreover, there are limited online user-friendly randomization tools. Thus, we developed a free robust randomization app (RRApp). RRApp incorporates 6 major randomization techniques: simple randomization, stratified randomization, block randomization, permuted block randomization, stratified block randomization, and stratified permuted block randomization. The design phase has been completed, including robust server scripts and a straightforward user-interface using the “shiny” package in R. Randomization schemes generated in RRApp can be input directly into the Research Electronic Data Capture (REDCap) system. RRApp has been evaluated by biostatisticians and junior clinical faculty at the Icahn School of Medicine at Mount Sinai. Constructive feedback regarding the quality and functionality of RRApp was also provided by attendees of the 2016 Association for Clinical and Translational Statisticians Annual Meeting. RRApp aims to educate early stage clinical trialists about the importance of randomization, while simultaneously assisting them, in a user-friendly fashion, to generate reproducible randomization schemes.
ABCB1 Genetic Variation Influences the Toxicity and Clinical Outcome of Patients with Androgen-Independent Prostate Cancer Treated with Docetaxel

Purpose: Polymorphisms that are associated with ABCB1 expression and function may be linked to treatment efficacy and the development of neutropenia and neurotoxicity in patients with androgen-independent prostate cancer receiving docetaxel. Experimental Design: Patients with androgen-independent prostate cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n = 50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by direct sequencing, and diplotypes were constructed using an EM algorithm. The data were then compared with duration to onset of peripheral neuropathy, neutropenia grade, and survival after docetaxel. Results: For patients receiving docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G-3435C linked alleles had improved overall survival after treatment (P = 0.0017). Additionally, patients treated with docetaxel and thalidomide carrying a diplotype consisting of the 2677T-3435T haplotype had a shorter median survival (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel and thalidomide cohort. Among both treatment arms together, individuals carrying the 2677GG genotype also had a significantly longer time to neuropathy (P = 0.035). Finally, there was a strong trend toward patients carrying the 2677TT-3435TT diplotype having higher grades of neutropenia (P = 0.053). Conclusion: The data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants with ensuing negative implications for docetaxel treatment in patients carrying ABCB1 variant genotypes.
Fear conditioning in adolescents with anxiety disorders: results from a novel experimental paradigm.

OBJECTIVE Considerable research examines fear conditioning in adult anxiety disorders but few studies examine youths. Adult data suggest that anxiety disorders involve elevated fear but intact differential conditioning. We used a novel paradigm to assess fear conditioning in pediatric anxiety patients. METHOD Sixteen individuals with anxiety disorders and 38 healthy comparisons viewed two photographs of actresses displaying neutral expressions. One picture served as the conditioned stimulus (CS), paired with a fearful expression and a shrieking scream (CS+), whereas the other picture served as a CS unpaired with the aversive outcome (CS-). Conditioning was indexed by self-reported fear. Subjects participated in two visits involving conditioning and extinction trials. RESULTS Both groups developed greater fear of the CS+ relative to CS-. Higher fear levels collapsed across each CS characterized anxious relative to healthy subjects, but no significant interaction between group and stimulus type emerged. Fear levels at visit 1 predicted avoidance of visit 2. Fear levels to both CS types showed stability even after extinction. CONCLUSIONS Consistent with adult data, pediatric anxiety involves higher fear levels following conditioning but not greater differential conditioning. Extending these methods to neuroimaging studies may elucidate neural correlates of fear conditioning. Implications for exposure therapies are discussed.
The Impact of Support at the Workplace on Transfer of Training: A Study of an Indian Manufacturing Unit

This study aims to assess the individual impacts of two components of support at the workplace, namely, support from peers and supervisor, on transfer of training in a post-training environment. Mediation by motivation to transfer in the relationship of supervisor and peer support with transfer of training has also been examined. Data on 149 respondent employees working in a manufacturing unit owned by a leading player in the power transmission business in India has been subject to hierarchical regression analysis. Results confirm the key role of supervisor support in transfer of learned skills. However, the impact of peers on transfer is found to be greater than that of supervisors. The findings prompt us to recommend that peers should be involved in publicizing post-training experiences and benefits. Organizations and supervisors should encourage peers to motivate employees in applying training skills to the job by means of rewards and recognition. Overall the results contribute to a better understanding of support at workplace as a predictor of transfer.
Bone Transport for Postinfectious Segmental Tibial Bone Defects With a Combined Ilizarov/Taylor Spatial Frame Technique

Objective: To assess and compare the results of trifocal (two-level bone lengthening with compression at the nonunion site) and bifocal (one-level bone lengthening with compression at the nonunion site) bone transport using the Taylor Spatial Frame (TSF; Smith and Nephew, Inc, Memphis, TN) for postinfectious segmental tibial bone defects. Design: Retrospective study of 12 patients with atrophic tibial nonunions. These patients were treated with resection of the nonunion followed by bone transport using the TSF for the segmental tibial bone defects. All patients were treated by the same surgeon (F.S.). Setting: Level I trauma center. Patients/Participants: Twelve consecutive patients treated for postinfectious segmental tibial bone defects between November 2004 and September 2007. Intervention: All patients were treated using the TSF for a trifocal or bifocal technique of bone transport along with associated soft tissue reconstructive surgeries. All patients were additionally treated with 45 days of culture-specific antibiotics. Outcome Measurement: All patients were evaluated by the guidelines of the Association for the Study of the Method of Ilizarov. Results and Conclusion: All patients achieved complete union and eradication of infection. The results were evaluated according to Association for the Study of the Method of Ilizarov criteria: 83% were excellent and 17% were good in terms of bony outcomes; functional results were excellent in 50%, good in 42%, and fair in 8%. Combined Ilizarov/TSF trifocal and bifocal techniques for the treatment of segmental tibial bone defects achieve union without malalignment of the mechanical axis.
Holistic Processing for Other-Race Faces in Chinese Participants Occurs for Upright but Not Inverted Faces

Recent evidence suggests stronger holistic processing for own-race faces may underlie the own-race advantage in face memory. In previous studies Caucasian participants have demonstrated larger holistic processing effects for Caucasian over Asian faces. However, Asian participants have consistently shown similar sized effects for both Asian and Caucasian faces. We investigated two proposed explanations for the holistic processing of other-race faces by Asian participants: (1) greater other-race exposure, (2) a general global processing bias. Holistic processing was tested using the part-whole task. Participants were living in predominantly own-race environments and other-race contact was evaluated. Despite reporting significantly greater contact with own-race than other-race people, Chinese participants displayed strong holistic processing for both Asian and Caucasian upright faces. In addition, Chinese participants showed no evidence of holistic processing for inverted faces arguing against a general global processing bias explanation. Caucasian participants, in line with previous studies, displayed stronger holistic processing for Caucasian than Asian upright faces. For inverted faces there were no race-of-face differences. These results are used to suggest that Asians may make more general use of face-specific mechanisms than Caucasians.
Learning from other people's fear: amygdala-based social reference learning in social anxiety disorder

Background Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions? Method A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions. Results During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions. Conclusions These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.
‘We are given a body to walk this earth’: the body pride experiences of young Aboriginal men and women

Abstract Positive body image was initially conceptualised as the absence of negative body image, but it is now considered a unique and multifaceted construct. Within this new and flourishing body of literature, researchers have focused on various facets of positive body image including body pride. Body pride has been identified as a construct that may be instrumental to health and it is necessary to deepen understandings of this construct among culturally diverse populations. The purpose of this research was to explore the body pride experiences of young Aboriginal men and women. Using a community-based participatory research approach, eight young men and women that self-identify as Aboriginal (ages 20–25 years) shared their experiences of body pride through one-on-one interviews and photographs. A qualitative content analysis highlighted five themes representing body pride: (1) ‘your mind, your spirit, your body’, (2) ‘it’s a practice’, (3) ‘learned from my culture’, (4) ‘getting caught up in this western world’, and (5) ‘powerful’. This research makes a significant contribution to the body image literature in that it provides in-depth insight into the overlooked experiences of Aboriginal peoples and highlights culturally specific opportunities that may foster experiences of body pride.
Mortality results from a randomized prostate-cancer screening trial.

BACKGROUND The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. METHODS From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. RESULTS In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. CONCLUSIONS After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.)
Divergence of the multilevel Monte Carlo Euler method for nonlinear stochastic differential equations

The Euler-Maruyama scheme is known to diverge strongly and numerically weakly when applied to nonlinear stochastic differential equations (SDEs) with superlinearly growing and globally one-sided Lipschitz continuous drift coefficients. Classical Monte Carlo simulations do, however, not suffer from this divergence behavior of Euler's method because this divergence behavior happens on rare events. Indeed, for such nonlinear SDEs the classical Monte Carlo Euler method has been shown to converge by exploiting that the Euler approximations diverge only on events whose probabilities decay to zero very rapidly. Significantly more efficient than the classical Monte Carlo Euler method is the recently introduced multilevel Monte Carlo Euler method. The main observation of this article is that this multilevel Monte Carlo Euler method does - in contrast to classical Monte Carlo methods - not converge in general in the case of such nonlinear SDEs. More precisely, we establish divergence of the multilevel Monte Carlo Euler method for a family of SDEs with superlinearly growing and globally one-sided Lipschitz continuous drift coefficients. In particular, the multilevel Monte Carlo Euler method diverges for these nonlinear SDEs on an event that is not at all rare but has probability one. As a consequence for applications, we recommend not to use the multilevel Monte Carlo Euler method for SDEs with superlinearly growing nonlinearities. Instead we propose to combine the multilevel Monte Carlo method with a slightly modified Euler method. More precisely, we show that the multilevel Monte Carlo method combined with a tamed Euler method converges for nonlinear SDEs with globally one-sided Lipschitz continuous drift coefficients and preserves its strikingly higher order convergence rate from the Lipschitz case.
Leadership and post-traumatic stress disorder: are soldiers’ perceptions of organizational justice during deployment protective?

ABSTRACT Background: Soldiers’ perception of leadership during military deployment has gained research attention as a potentially modifiable factor to buffer against the development of postdeployment post-traumatic stress disorder (PTSD). Within nonmilitary research, the organizational justice (OJ) framework, i.e. distributive justice, procedural justice (PJ) and interactional justice (IJ), has been found to relate to mental health outcomes. Aspects of OJ may, therefore, be protective against PTSD. Objectives: We examined the prospective relationship between aspects of OJ, namely the perceptions of PJ and IJ by subordinate soldiers without leadership obligations in relationship to immediate superiors and PTSD. Method: Participants were soldiers (n = 245) deployed to Helmand Province in Afghanistan in 2009. Logistic regression procedures were used. The primary analysis measured PTSD cases using the Structured Clinical Interview for DSM-IV-TR Axis-I Disorder (SCID) 2½ years after homecoming. PJ/IJ was measured during deployment with a 6-item composite measure ranging from 0 to 12. Supplementary primary analyses were performed with PJ/IJ measured before and immediately after deployment. A secondary PJ/IJ analysis also tested against four postdeployment measures with the Post-Traumatic Stress Disorder Checklist Civilian (PCL-C) dichotomized at screening symptom levels. Results: Higher levels of perceived PJ/IJ for soldiers without leadership obligations during deployment had a prospective relation (OR = 0.86, 95% CI = 0.75–0.98) with PTSD on the SCID 2½ years after homecoming after adjustment for factors including predeployment PTSD symptoms, trauma and combat exposure, and state affectivity. Similar results were found by measuring PJ/IJ before (OR = 0.83, 95% CI = 0.71–0.95) but not immediately after homecoming (OR = 0.97, 95% CI = 0.85–1.11). A relationship with PTSD symptoms at the screening level at the four measurements of PCL-C was found, but only when predeployment PTSD symptoms were not controlled for. Conclusions: These results suggest that PJ/IJ exercised by superiors in relation to military deployments may protect subordinate soldiers against the development of postdeployment PTSD.
Trust, Reciprocity, and Betrayal Aversion: Theoretical and Experimental Insights

We propose that there are three determinants of sender behavior in trust games: Beliefs re-garding the amounts returned, risk aversion, and reciprocity. Particularly, we are interested in the role of reciprocity because the possibility of negative expected reciprocal utility may lead to betrayal-averse sender behavior, i.e. to a situation where reciprocal subjects send less money than solely selfish ones. In our experiment, most subjects show distinct social preferences in the receiver role, but in the sender role they do not distinguish between a standard trust game with a human partner and a non-social, lottery-like setting, where a computer plays the role of the receiver. This means that the relevance of reciprocity considerations under uncertainty might be fundamentally different from those when no uncertainty is present. Furthermore, we find that sendings are mainly driven by overoptimistic beliefs. We use a modified version of the reciprocity model of Dufwenberg and Kirchsteiger [Games Econ. Beh. 47 (2004) 268] to explain our results and thereby show why reciprocal and selfish subjects almost do not differ in their sending behavior if one controls for beliefs and risk aversion. For other experimental settings, our model does predict differing behavior, which is in line with findings reported in the literature.
Blocking cannabinoid CB1 receptors for the treatment of nicotine dependence: insights from pre‐clinical and clinical studies

Tobacco use is one of the leading preventable causes of death in developed countries. Since existing medications are only partially effective in treating tobacco smokers, there is a great need for improved medications for smoking cessation. It has been recently proposed that cannabinoid CB1 receptor antagonists represent a new class of therapeutic agents for drug dependence, and notably, nicotine dependence. Here, we will review current evidence supporting the use of this class of drugs for smoking cessation treatment. Pre‐clinical studies indicate that nicotine exposure produces changes in endocannabinoid content in the brain. In experimental animals, N‐piperidinyl‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methylpyrazole‐3‐carboxamide (rimonabant, SR141716) and N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251), two cannabinoid CB1 receptor antagonists, block nicotine self‐administration behavior, an effect that may be related to the blockade of the dopamine‐releasing effects of nicotine in the brain. Rimonabant also seems efficacious in decreasing the influence of nicotine‐associated stimuli over behavior, suggesting that it may act on two distinct neuronal pathways, those implicated in drug‐taking behavior and those involved in relapse phenomena. The utility of rimonabant has been evaluated in several clinical trials. It seems that rimonabant is an efficacious treatment for smoking cessation, although its efficacy does not exceed that of nicotine‐replacement therapy and its use may be limited by emotional side effects (nausea, anxiety and depression, mostly). Rimonabant also appears to decrease relapse rates in smokers. These findings indicate significant, but limited, utility of rimonabant for smoking cessation.
Variable manifestations, diverse seroreactivity and post-treatment persistence in non-human primates exposed to Borrelia burgdorferi by tick feeding

The efficacy and accepted regimen of antibiotic treatment for Lyme disease has been a point of significant contention among physicians and patients. While experimental studies in animals have offered evidence of post-treatment persistence of Borrelia burgdorferi, variations in methodology, detection methods and limitations of the models have led to some uncertainty with respect to translation of these results to human infection. With all stages of clinical Lyme disease having previously been described in nonhuman primates, this animal model was selected in order to most closely mimic human infection and response to treatment. Rhesus macaques were inoculated with B. burgdorferi by tick bite and a portion were treated with recommended doses of doxycycline for 28 days at four months post-inoculation. Signs of infection, clinical pathology, and antibody responses to a set of five antigens were monitored throughout the ~1.2 year study. Persistence of B. burgdorferi was evaluated using xenodiagnosis, bioassays in mice, multiple methods of molecular detection, immunostaining with polyclonal and monoclonal antibodies and an in vivo culture system. Our results demonstrate host-dependent signs of infection and variation in antibody responses. In addition, we observed evidence of persistent, intact, metabolically-active B. burgdorferi after antibiotic treatment of disseminated infection and showed that persistence may not be reflected by maintenance of specific antibody production by the host.