Profile of nelarabine: use in the treatment of T-cell acute lymphoblastic leukemia

Nelarabine is the prodrug of 9-β-arabinofuranosylguanine (ara-G) and is therapeutically classified as a purine nucleoside analog. Nelarabine is converted to ara-G by adenosine deaminase and transported into cells by a nucleoside transporter. Ara-G is subsequently phosphorylated to ara-G triphosphate (ara-GTP), thereby initiating the therapeutic effect by inhibiting DNA synthesis. Nelarabine has been extensively studied in regards to its pharmacokinetics, and the data have demonstrated that ara-GTP preferentially accumulates in malignant T-cells. Clinical responses to nelarabine have been demonstrated in various T-cell malignancies and appear to correlate with a relatively high intracellular concentration of ara-GTP compared to nonresponders. Therefore, this unique drug feature of nelarabine accounts for clinical utilization in treating adult and pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. Neuropathy is the most predominant adverse effect associated with nelarabine and the incidence correlates with the dose administered. Myelosuppression has been observed, with thrombocytopenia and neutropenia as the most common hematologic complications. This article reviews the pharmacology, mechanism of action, and pharmacokinetic properties of nelarabine, as well as nelarabine’s clinical efficacy in T-ALL, T-LBL, and other hematologic malignancies. The toxicity profile, dosage, and administration, and areas of ongoing and future research, are also presented

Contribution of walking to school to individual and population moderate-vigorous intensity physical activity

PURPOSE: This study estimated the contribution of walking to/from school to objectively measured daily moderate-vigorous intensity physical activity (MVPA) in individuals and populations. METHODS: MEDLINE, PsycINFO and SPORTDiscus were systematically searched up to February 2015. Two reviewers independently screened titles/abstracts/full-text articles, and assessed study quality. RESULTS: Of 2430 records, 116 were eligible for full-text screening. Twelve studies met the inclusion criteria of reporting objectively obtained measures of MVPA (total and while walking to/from school) in children and adolescents. The weighted mean MVPA accumulated in walking to and from school was 17 minutes per day in primary school pupils (9 samples, n=3422) and 13 minutes per day in high school pupils (4 samples, n=2600). Pooled analysis suggested that walking to and from school contributed 23% and 36% of MVPA on schooldays in primary school age children and high school pupils, respectively. All included studies were of high methodological quality. CONCLUSIONS: Walking to and from school makes a meaningful contribution to individual schoolday MVPA for active commuters in western countries. Since schooldays represent only around half of all days, and prevalence of walking to school is low in many countries, the contribution of walking to school to population MVPA is probably low

Remembering Your Roots: The Role of Horticulture Therapy in People Living with Dementia

Introduction: Dementia is a debilitating disease affecting over 50 million people. Major challenges facing patients with dementia lie in the impact of the behavioral and psychological symptoms of dementia (BPSD). The American Geriatrics Society and Dementia Action Alliance recommend against the use of antipsychotics as first-line treatment. Antipsychotics often fail to treat BPSD whereas nonmedication practices such as horticulture therapy may lessen BPSD. Guideline evidence has provided a unique opportunity for public health officials to assist in filling this vital role in the approach to BPSD management.Methods: Several studies and meta-analyses were reviewed to determine the effectiveness of horticulture therapy in managing BPSD, and evidence supports horticulture therapy as an effective method of addressing BPSD.Results: The benefits of horticulture therapy extend beyond addressing only BPSD; through multisensory stimulation, patients have increased physical activity, reduced stress, and improved sleep. Horticulture therapy has been shown to decrease the sense of loss and reestablish the patient in a familiar nurturing role, providing the patient with a sense of purpose.Conclusion: Stakeholders within the public health sector are strategically positioned to implement evidence-based interventions that address the unmet needs for the care of dementia within the community

Isolating endogenous visuo-spatial attentional effects using the novel visual-evoked spread spectrum analysis (VESPA) technique

In natural visual environments, we use attention to select between relevant and irrelevant stimuli that are presented simultaneously. Our attention to objects in our visual field is largely controlled endogenously, but is also affected exogenously through the influence of novel stimuli and events. The study of endogenous and exogenous attention as separate mechanisms has been possible in behavioral and functional imaging studies, where multiple stimuli can be presented continuously and simultaneously. It has also been possible in electroencephalogram studies using the steady-state visual-evoked potential (SSVEP); however, it has not been possible in conventional event-related potential (ERP) studies, which are hampered by the need to present suddenly onsetting stimuli in isolation. This is unfortunate as the ERP technique allows for the analysis of human physiology with much greater temporal resolution than functional magnetic resonance imaging or the SSVEP. While ERP studies of endogenous attention have been widely reported, these experiments have a serious limitation in that the suddenly onsetting stimuli, used to elicit the ERP, inevitably have an exogenous, attention-grabbing effect. Recently we have shown that it is possible to derive separate event-related responses to concurrent, continuously presented stimuli using the VESPA (visual-evoked spread spectrum analysis) technique. In this study we employed an experimental paradigm based on this method, in which two pairs of diagonally opposite, non-contiguous disc-segment stimuli were presented, one pair to be ignored and the other to be attended. VESPA responses derived for each pair showed a strong modulation at 90–100 ms (during the visual P1 component), demonstrating the utility of the method for isolating endogenous visuospatial attention effects

“Structural Dissatisfaction”: academics on safari in the novels of Jennifer Egan

Jennifer Egan's acclaimed 2010 novel, A Visit from the Goon Squad, is a text populated by a disproportionately high number of, often unfulfilled, postgraduate researchers: “I'm in the PhD program at Berkeley”, proclaims Mindy; “Joe, who hailed from Kenya [...] was getting his PhD in robotics at Columbia”; “Bix, who's black, is spending his nights in the electrical-engineering lab where he's doing his PhD research”; while only Rebecca “was an academic star”. Indeed, in this text, academia seems a place of misery, of “harried academic slaving”, and, ultimately, of “immaturity and disastrous choices”. Over the course of this article I will demonstrate that, in fact, Egan's critique of the university is an immanent meta-critique. While the history of the campus novel is often premised on hermetically sealing the campus (the genre usually functions through an explicit focus on a delineated campus space or, at least, predominantly upon the social milieu of the academy), Egan's novels seem to play on bursting the very notions of inside and outside that facilitate this genre, blurring the boundaries between fiction and critique; the leeching of the university into everyday life. She also, simultaneously, however, critiques the structures of labour upon which much of the academy is founded. While I will move towards Egan's latest novel, A Visit From the Goon Squad, throughout this article I will make reference to her entire novelistic canon, demonstrating that the treatment of academics throughout cannot be viewed as merely incidental, even if the appearances of such characters are sporadic and diffuse

Principles and practices of training for soccer

The complexity of the physical demands of soccer requires the completion of a multi-component training programme. The development, planning, and implementation of such a programme are difficult due partly to the practical constraints related to the competitive schedule at the top level. The effective planning and organisation of training are therefore crucial to the effective delivery of the training stimulus for both individual players and the team. The aim of this article is to provide an overview of the principles of training that can be used to prepare players for the physical demands of soccer. Information relating to periodisation is supported by an outline of the strategies used to deliver the acute training stress in a soccer environment. The importance of monitoring to support the planning process is also reviewed

Motor vehicle accidents in patients with an implantable cardioverter-defibrillator

Objectives.This study was designed to examine driving safety in patients at risk for sudden death after implantation of a cardioverter-defibrillator.Background.Cardioverter-defibrillators are frequently implanted in patients at high risk for sudden death. Despite concern about the safety of driving in these patients, little is known about their actual motor vehicle accident rates.Methods.Surveys were sent to all 742 physicians in the United States involved in cardioverter-defibrillator implantation and follow-up. Physicians were questioned about numbers of patients followed up, numbers of fatal and nonfatal accidents, physician recommendations to patients about driving and knowledge of state driving laws.Results.Surveys were returned by 452 physicians (61%). A total of 30 motor vehicle accidents related to shocks from implantable defibrillators were reported by 25 physicians over a 12-year period from 1980 to 1992. Of these, nine were fatal accidents involving eight patients with a defibrillator and one passenger in a car driven by a patient. No bystanders were fatally injured. There were 21 nonfatal accidents involving 15 patients, 3 passengers and 3 bystanders. The estimated fatality rate for patients with a defibrillator, 7.5/100,000 patient-years, is significantly lower than that for the general population (18.4/100,000 patient-years, p < 0.05). The estimated injury rate, 17.6/100,000 patient-years, is also significantly lower than that for the general public (2,224/100,000 patient-years, p < 0.05). Only 10.5% (30 of 286) of all defibrillator discharges during driving resulted in accidents. Regarding physician recommendations, most physicians (58.1%) ask their patients to wait a mean (± SD) of 7.3 ± 3.4 months after implantation or a shock before driving again.Conclusions.The motor vehicle accident rate caused by discharge from an implantable cardioverter-defibrillator is low. Although restricting driving for a short period of time after implantation may be appropriate, excessive restrictions or a total ban on driving appears to be unwarranted

Contribution of walking to school to individual and population moderate-vigorous intensity physical activity:Systematic review and meta-analysis

Purpose: This study estimated the contribution of walking to/from school to objectively measured daily moderate-vigorous intensity physical activity (MVPA) in individuals and populations. Methods: MEDLINE, PsycINFO and SPORTDiscus were systematically searched up to February 2015. Two reviewers independently screened titles/abstracts/full-text articles, and assessed study quality. Results: Of 2430 records, 129 were eligible for full-text screening. Twelve studies met the inclusion criteria of reporting objectively obtained measures of MVPA (total and while walking to/from school) in children and adolescents. The weighted mean MVPA accumulated in walking to and from school was 17 min/day in primary school pupils (9 samples, n = 3422) and 13 min/day in high school pupils (4 samples, n = 2600). Pooled analysis suggested that walking to and from school contributed 23% and 36% of MVPA on schooldays in primary school age children and high school pupils, respectively. All included studies were of high methodological quality. Conclusions: Walking to and from school makes a meaningful contribution to individual schoolday MVPA for active commuters in western countries. Since schooldays represent only around half of all days, and prevalence of walking to school is low in many countries, the contribution of walking to school to population MVPA is probably low

An Avatar-Led Digital Smoking Cessation Program for Sexual and Gender Minority Young Adults: Intervention Development and Results of a Single-Arm Pilot Trial

BACKGROUND: Sexual and gender minority young adults have a high prevalence of smoking and unique barriers to accessing tobacco treatment. OBJECTIVE: To address these challenges as well as their preferences for sexual and gender minority-targeted interventions and digital programs, we developed and evaluated the acceptability, preliminary efficacy, and impact on theory-based change processes of an acceptance and commitment therapy-based digital program called Empowered, Queer, Quitting, and Living (EQQUAL). METHODS: Participants (n=22) of a single-arm trial conducted to evaluate the program were young adults, age 18 to 30 years, who self-identified as sexual and gender minority individuals and smoked at least one cigarette per day. All participants received access to the EQQUAL program. Participants completed web-based surveys at baseline and at a follow-up 2 months after enrollment. We verified self-reported smoking abstinence with biochemical testing; missing data were counted as smoking or using tobacco. RESULTS: For young adults who logged in at least once (n=18), the mean number of log-ins was 5.5 (SD 3.6), mean number of sessions completed was 3.1 (SD 2.6), and 39% (7/18) completed all 6 sessions. Overall, 93% of participants (14/15) were satisfied with the EQQUAL program, 100% (15/15) found it easy to use, and 100% (15/15) said it helped them be clearer about how to quit. Abstinence from smoking or using tobacco was confirmed with biochemical testing for 23% of participants (5/22). Both quantitative and qualitative results suggested a positive overall response to the avatar guide, with areas for future improvement largely centered on the avatar\u27s appearance and movements. CONCLUSIONS: Treatment acceptability of EQQUAL was very promising. The rate of abstinence, which was biochemically confirmed, was 3 times higher than that of the only other digital program to date that has targeted sexual and gender minority young adults and 6 to 13 times higher than those of nontargeted digital smoking interventions among sexual and gender minority young adults. Planned improvements for the next iteration of the program include making the avatar\u27s movements more natural; offering multiple avatar guides with different on characteristics such as race, ethnicity, and gender identity from which to choose; and providing a support forum for users to connect anonymously with peers

Match physical performance of elite female soccer players during international competition.

The purpose of the present study was to provide a detailed analysis of the physical demands of competitive international female soccer match-play. A total of 148 individual match observations were undertaken on 107 outfield players competing in competitive international matches during the 2011-2012 and 2012-2013 seasons, using a computerized tracking system (Prozone Sports Ltd., Leeds, England). Total distance (TD) and total high-speed running distances (THSR) were influenced by playing position, with central midfielders (CM) completing the highest (10985±706 m and 2882±500 m) and central defenders (CD) the lowest (9489±562 m and 1901±268 m) distances, respectively. Greater total very high-speed running (TVHSR) distances were completed when a team was without (399±143 m) compared to with (313±210 m) possession of the ball. The majority of sprints were over short distances with 76 % and 95 % being less than 5 m and 10 m, respectively. Between half reductions in physical performance were present for all variables, independent of playing position. The current study provides novel findings regarding the physical demands of different playing positions in competitive international female match-play and provides important insights for physical coaches preparing elite female players for competition