Publications by authors named "Laura Turner"

28 Publications

  • Page 1 of 1

A randomized controlled trial of exercise on augmenting the effects of cognitive remediation in persons with severe mental illness.

J Psychiatr Res 2021 07 13;139:38-46. Epub 2021 May 13.

Center for Psychiatric Rehabilitation, Boston University, United States; Department of Occupational Therapy and Psychological and Brain Sciences, Boston University, United States. Electronic address:

Background: Preliminary evidence suggests that aerobic exercise may augment the effects of cognitive remediation on improving cognitive functioning in severe mental illness. It has also been hypothesized that increases in cognitive functioning associated with adding exercise are mediated by increases in brain derived neurotrophic factor (BDNF). However, rigorous controlled trials are lacking.

Methods: A randomized controlled trial was conducted to explore whether adding a 30-h aerobic exercise program over 10 weeks to an equally intensive cognitive remediation program (CR + E) improved cognitive functioning more than cognitive remediation alone (CR-Only). Thirty-four participants with schizophrenia or bipolar disorder were randomly assigned to CR + E or CR-Only, and cognitive functioning was assessed at baseline and post-treatment. Total and mature BDNF were measured in blood serum at baseline, Week-5 pre- and post-exercise, and Week-10 pre- and post-exercise.

Results: Participants in both conditions had high levels of engagement in the interventions and improved significantly in cognitive functioning, but did not differ in amount of cognitive change. The groups also did not differ in changes in BDNF from pre-to post-exercise at Weeks 5 or 10, nor in resting BDNF levels. Exploratory analyses indicated that higher body mass index (BMI) significantly predicted attenuated improvement in cognitive functioning for both groups.

Discussion: Exercise did not augment the effects of cognitive remediation in persons with severe mental illness, possibly because the cognitive remediation program resulted in strong gains in cognitive functioning. Moderate aerobic exercise does not appear to reliably increase BDNF levels in persons with severe mental illness. CLINICALTRIALS.

Gov Identifier: NCT02326389.
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http://dx.doi.org/10.1016/j.jpsychires.2021.04.033DOI Listing
July 2021

Scaling Up Behavioral Skills Training: Effectiveness of Large-Scale and Multiskill Trainings.

Behav Anal Pract 2021 Mar 2;14(1):36-50. Epub 2020 Nov 2.

Department of Counseling and Applied Behavioral Studies, University of Saint Joseph, 1678 Asylum Dr., West Hartford, CT 06117 USA.

We used behavioral skills training (BST) to teach multiple skills to 2 cohorts of 18 participants. BST consisted of the standard 4 components: (a) didactic instruction, (b) modeling, (c) role-play, and (d) feedback, modified to be delivered in a large-group format. All components were provided by 1 trainer, simultaneously to all participants, with peers delivering feedback during role-plays. Across 4 targeted skills (e.g., discrete-trial teaching), the average performance of Cohort 1 improved from less than 60% correct implementation in baseline to a performance of between 85% and 100% correct, across participants, following BST. We used social validity data collected from Cohort 1 to modify the length of instruction across skills for Cohort 2. BST was similarly effective for Cohort 2, with a decrease in the additional training required for trainees to demonstrate the skill in a novel role-play scenario or with a client. Implications for effectively scaling up BST are discussed.
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http://dx.doi.org/10.1007/s40617-020-00480-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900374PMC
March 2021

Acute kidney injury, stroke and death after cardiopulmonary bypass surgery: the role of perfusion flow and pressure.

Perfusion 2021 01 9;36(1):78-86. Epub 2020 Jun 9.

Department of Cardiothoracic Surgery, Flinders Medical Centre and Flinders University, Adelaide, SA, Australia.

Introduction: Acute kidney injury after cardiopulmonary bypass surgery is associated with morbidity and mortality. This study aims to evaluate the role of low perfusion flow and pressure in the development of cardiopulmonary bypass-associated acute kidney injury, stroke and death, using multicentre registry data.

Methods: We identified patients from the Australian and New Zealand Collaborative Perfusion Registry who underwent coronary artery bypass grafting and/or valvular surgery between 2008 and 2018. Primary predictor variables were the length of time the perfusion flow was <1.6 L/min/m and the length of time perfusion pressure was < 50mmHg. The primary outcome was new postoperative acute kidney injury defined by the risk-injury-failure-loss-end stage criteria. Secondary outcomes were stroke and in-hospital death. The influence of perfusion flow and pressure during cardiopulmonary bypass on the primary and secondary outcomes was estimated using separate multivariate models.

Results: A total of 16,356 patients were included. The mean age was 66 years and 75% were male. Acute kidney injury was observed in 1,844 patients (11%), stroke in 204 (1.3%) and in-hospital death in 286 (1.8%). Neither the duration of the time spent for perfusion flow (<1.6 L/minute/m) nor the duration of the time spent for perfusion pressure (<50 mmHg) was associated with postoperative acute kidney injury, stroke or death in adjusted models.

Conclusions: Neither low perfusion pressure nor low perfusion flow during cardiopulmonary bypass were predictive of postoperative acute kidney injury, stroke or death.
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http://dx.doi.org/10.1177/0267659120924919DOI Listing
January 2021

Membership Trends in the Academic Pediatric Association From 2009 to 2018.

Acad Pediatr 2020 08 29;20(6):816-822. Epub 2020 Feb 29.

Department of Pediatrics (TR Coker), University of Washington, Seattle Children's Research Institute, Seattle, Wash; Odessa Brown Children's Clinic (TR Coker), Seattle Wash.

Objective: To describe changes in the racial and ethnic diversity of the membership of a national academic health professional organization, the Academic Pediatric Association (APA) from 2009 to 2018.

Methods: Administrative data from the APA was used for the study. Our sample was limited to dues-paying members of the APA with complete profile information. Data on race/ethnicity was collected by self-report and categorized as White, Hispanic, Black, Asian, or other. Gender was obtained by self-report (male/female). Membership type included physician, non-physician, or trainee and was provided by self-report. Age was calculated by subtracting the dues year from the year of birth. Descriptive statistics were used. Log-linear models were used to describe changes in membership race/ethnicity and expressed as relative risk.

Results: Three thousand one hundred and ninety-six unique individuals were included. Enrollment in the APA increased from 1429 in 2009 to 1803 in 2018. Females represented 68% of the sample. Six percent of the sample identified as Black, 5% as Hispanic, 12% as Asian, and 74% as White. Using log-linear models, the proportion of members identifying as Black increased from 4% to 6% (P < .001), Asian 8% to 13% (P < .001) and Hispanic increased 4% to 5% (P = .17).

Conclusions: The APA has increased the representation of underrepresented racial and ethnic minorities in medicine within its membership. The APA and other academic pediatric professional organizations, can build on these current trends by continuing to invest in programming focused on increasing racial/ethnic minority groups underrepresented in medicine.
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http://dx.doi.org/10.1016/j.acap.2020.02.024DOI Listing
August 2020

Improving body functions through participation in community activities among young people with physical disabilities.

Dev Med Child Neurol 2020 05 31;62(5):640-646. Epub 2019 Oct 31.

CanChild Centre for Childhood Disability Research, McMaster University, Hamilton, ON, Canada.

Aim: To examine the impact of engagement in a self-chosen community-based activity on three relevant body functions (motor, cognitive, and affective) as well as on the performance of the selected activity.

Method: An individual-based interrupted time series design with multiple baselines was used. Seven young people (four males, three females) aged 15 to 25 years (median 18y; interquartile range 17-20y) with physical disabilities participated in an 8-week community activity of choice (e.g. swimming, playing piano). Change in three relevant body functions, underpinning the specific chosen activity, including motor (e.g. Functional Reach Test, Trunk Impairment Scale, dynamometers), cognitive and affective (Behavior Assessment System for Children), as well as activity performance (Canadian Occupational Performance Measure) were measured repeatedly, providing individual outcome trajectories. Linear and mixed-effects models were used.

Results: Significant improvements in at least one aspect of motor function (6 out of 6), cognition (3 out of 3), affect (5 out of 7), and performance (7 out of 7) were observed. Specifically, the intervention had a moderate to large effect on hyperactivity (1.45, 95% confidence interval [CI] 1.0-1.9) with a smaller effect on anxiety (0.21, 95% CI 0.10-0.32) and inadequacy (0.21, 95% CI 0.02-0.39). Concurrently, a notable effect size for activity performance (4.61, 95% CI 0.76-8.46) was observed. Average change across motor outcomes was substantial (3.7 SDs from baseline), yet non-significant.

Interpertation: Findings provide initial evidence of the benefits resulting from participation-based interventions, emphasizing the merit of meaningful 'real-life' young people-engaging therapy.

What This Paper Adds: Participation-based interventions can impact body-function level outcomes. Significant improvements in the performance of chosen activities were observed. Significant improvements were also seen in cognitive and affective body functions. Improvements in motor-related outcomes were substantial but not statistically significant.
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http://dx.doi.org/10.1111/dmcn.14382DOI Listing
May 2020

Re: The Influence of Online Forums on Radiation Oncology Residency Program Selection.

Int J Radiat Oncol Biol Phys 2019 09;105(1):233

Epic Care - Partners in Comprehensive Care, Walnut Creek, California.

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http://dx.doi.org/10.1016/j.ijrobp.2019.05.038DOI Listing
September 2019

Trauma informed public health nursing visits to parents and children.

Public Health Nurs 2019 09 9;36(5):694-701. Epub 2019 Jul 9.

Department of Health Services, Sonoma County, Santa Rosa, California.

Adverse Childhood Experiences (ACEs) research has demonstrated a strong correlation between a traumatic childhood and poor health and social status in adulthood. Maternal/child Public Health Nursing (PHN) home visiting teams frequently encounter families experiencing trauma, thus offering a unique opportunity to assist parents in recognizing the potential harm such stress may have for their child. The Sonoma County Field Nursing team developed a trauma-informed model utilizing ACEs education in a self-reflective approach with parents to increase family resilience and reduce the risk for future childhood trauma. This paper presents the supporting research used to develop the trauma-informed approach and describes the execution of the model by the Sonoma County Field Nursing team.
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http://dx.doi.org/10.1111/phn.12634DOI Listing
September 2019

Parkinson's Disease and Driving Cessation: a Journey Influenced by Anxiety.

Clin Gerontol 2017 May-Jun;40(3):220-229. Epub 2016 Jul 28.

a The University of Queensland , Brisbane , Australia.

Objectives: In addition to the motor and cognitive symptoms that people with Parkinson's disease (PD) typically experience, psychiatric symptoms such as anxiety are also commonly experienced by people with PD. The overall purpose of the current study was to explore driving and driving cessation for people with PD and their families.

Methods: A descriptive phenomenological approach was employed using semi-structured interviews and 34 interviews were conducted overall (22 participants with PD and 12 family members).

Results: Experiences of anxiety and worry that had an impact on driving and driving cessation arose from the data, and this article specifically captured the lived experience of anxiety with driving and driving cessation for people with PD and their families.

Conclusions: Findings reveal that the experience of anxiety while driving, as well as anticipatory anxiety and/or worry related to driving cessation, affect the driving experiences and wellbeing of people with PD.

Clinical Implications: Implications of the study findings are outlined and aim to provide information about the needs to enable future clinical directions to be developed.
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http://dx.doi.org/10.1080/07317115.2016.1215365DOI Listing
June 2018

Young people have their say: What makes a youth-friendly general practice?

Aust Fam Physician 2017 Jan/Feb;46(1):70-74

Background: The health of young people can be considered an indicator of the health of Australia's future population. To improve access to healthcare, the perspectives of adolescents on the design and delivery of services need to be championed. The objective of this study was to identify what young people in north-west Tasmania value when seeking healthcare at general practices.

Methods: The study was conducted at a single high school in rural Tasmania. Students aged 16-18 years were invited to participate in an electronic survey seeking their views and preferences for presenting to their general practitioner (GP).

Results: One hundred and fifty-five students, with a mean age of 17 years, were surveyed. GPs were the usual healthcare providers for 98.4% of participants, and 86% stated that they would like to discuss mental health, substance use and sexual health with their GP.

Discussion: GPs can improve access to care for young people through good communications skills and treating young people as young adults.
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August 2017

Towards a Competency-Based, Ethical, and Socially Valid Approach to the Supervision of Applied Behavior Analytic Trainees.

Behav Anal Pract 2016 Dec 28;9(4):287-298. Epub 2016 Mar 28.

Clinical Solutions, Inc. and North East Educational and Developmental Support Center, 1120 Main Street, Tewksbury, MA 01940 USA.

Competency-based supervision of trainees has recently come to the forefront of behavior analytic practice; however, there are minimal data to support the effectiveness of various supervision practices on trainee outcomes. Accordingly, this paper is intended to spark further discussion and research activity regarding the supervision of those seeking to become Board Certified Behavior Analysts (BCBA). We present a practice model and considerations for supervising applied behavior analytic trainees consistent with the Behavior Analyst Certification Board (BACB) Supervisor Training Curriculum Outline (Behavior Analyst Certification Board, 2012b), the Professional and Ethical Compliance Code for Behavior Analysts (Behavior Analyst Certification Board, 2014), and extant literature from behavior analysis and related fields. Inherent to the current model is a focus on bi-directional feedback and collaboration between the supervisor and trainee to frequently evaluate the acceptability of the procedures, process, outcomes, and effectiveness of supervision. We present a Supervision Monitoring and Evaluation Form consistent with the current model and discuss the assumed importance of objective and subjective self-assessment of supervisor competence to the ultimate advancement of the practice of applied behavior analysis.
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http://dx.doi.org/10.1007/s40617-016-0121-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118253PMC
December 2016

SEPT8 modulates β-amyloidogenic processing of APP by affecting the sorting and accumulation of BACE1.

J Cell Sci 2016 06 15;129(11):2224-38. Epub 2016 Apr 15.

Institute of Biomedicine, School of Medicine, University of Eastern Finland, 70211 Kuopio, Finland Institute of Clinical Medicine - Neurology, School of Medicine, University of Eastern Finland and Department of Neurology, Kuopio University Hospital, 70211 Kuopio, Finland

Dysfunction and loss of synapses are early pathogenic events in Alzheimer's disease. A central step in the generation of toxic amyloid-β (Aβ) peptides is the cleavage of amyloid precursor protein (APP) by β-site APP-cleaving enzyme (BACE1). Here, we have elucidated whether downregulation of septin (SEPT) protein family members, which are implicated in synaptic plasticity and vesicular trafficking, affects APP processing and Aβ generation. SEPT8 was found to reduce soluble APPβ and Aβ levels in neuronal cells through a post-translational mechanism leading to decreased levels of BACE1 protein. In the human temporal cortex, we identified alterations in the expression of specific SEPT8 transcript variants in a manner that correlated with Alzheimer's-disease-related neurofibrillary pathology. These changes were associated with altered β-secretase activity. We also discovered that the overexpression of a specific Alzheimer's-disease-associated SEPT8 transcript variant increased the levels of BACE1 and Aβ peptides in neuronal cells. These changes were related to an increased half-life of BACE1 and the localization of BACE1 in recycling endosomes. These data suggest that SEPT8 modulates β-amyloidogenic processing of APP through a mechanism affecting the intracellular sorting and accumulation of BACE1.
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http://dx.doi.org/10.1242/jcs.185215DOI Listing
June 2016

The Benefits and Challenges of Preconsent in a Multisite, Pediatric Sickle Cell Intervention Trial.

Pediatr Blood Cancer 2016 09 15;63(9):1649-52. Epub 2016 Apr 15.

Pediatric Emergency Medicine, Medical College of Wisconsin, and the Children's Research Institute, Milwaukee, Wisconsin.

Enrollment of patients in sickle cell intervention trials has been challenging due to difficulty in obtaining consent from a legal guardian and lack of collaboration between emergency medicine and hematology. We utilized education and preconsent in a pediatric multisite sickle cell intervention trial to overcome these challenges. Overall, 48 patients were enrolled after being preconsented. Variable Institutional Review Board policies related to preconsent validity and its allowable duration decreased the advantages of preconsent at some sites. The utility of preconsent for future intervention trials largely depends on local Institutional Review Board policies. Preeducation may also benefit the consent process, regardless of site differences.
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http://dx.doi.org/10.1002/pbc.26013DOI Listing
September 2016

Focusing on the Environment to Improve Youth Participation: Experiences and Perspectives of Occupational Therapists.

Int J Environ Res Public Health 2015 Oct 23;12(10):13388-98. Epub 2015 Oct 23.

CBI Health Group, 3300 Bloor Street West, Toronto, ON M8X 2X2, Canada.

The environment plays a key role in supporting children's participation and can serve as a focus of intervention. This study aimed to elicit the perceptions and experiences of occupational therapists who had applied the PREP approach--Pathways and Resources for Engagement and Participation. PREP is a novel 12-week intervention for youth with physical disabilities, aimed at improving participation in leisure community-based activities by modifying aspects of the environment. Using a qualitative post-intervention only design, 12 therapists took part in individual semi-structured interviews, in which the therapists reflected on their experience using PREP to enable participation. A thematic analysis was conducted. Four themes emerged from the data; two of which were informative in nature, describing elements of the PREP intervention that target multi-layered composition of the environment and use strategies that involve leveraging resources and problem solving. The two remaining themes were reflective in nature, illustrating a new take on the Occupational Therapy role and re-positioning the concept of participation in therapy practices. Results emphasize aspects of the environment that can serve as effective targets of intervention, guided by the PREP approach. Findings can broaden the scope and focus of occupational therapy practice by redefining views on participation and the environment.
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http://dx.doi.org/10.3390/ijerph121013388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627037PMC
October 2015

Measuring Food Brand Awareness in Australian Children: Development and Validation of a New Instrument.

PLoS One 2015 29;10(7):e0133972. Epub 2015 Jul 29.

Prevention Research Collaboration, Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.

Background: Children's exposure to food marketing is one environmental determinant of childhood obesity. Measuring the extent to which children are aware of food brands may be one way to estimate relative prior exposures to food marketing. This study aimed to develop and validate an Australian Brand Awareness Instrument (ABAI) to estimate children's food brand awareness.

Methods: The ABAI incorporated 30 flashcards depicting food/drink logos and their corresponding products. An abbreviated version was also created using 12 flashcards (ABAI-a). The ABAI was presented to 60 primary school aged children (7-11 yrs) attending two Australian after-school centres. A week later, the full-version was repeated on approximately half the sample (n=27) and the abbreviated-version was presented to the remaining half (n=30). The test-retest reliability of the ABAI was analysed using Intra-class correlation coefficients. The concordance of the ABAI-a and full-version was assessed using Bland-Altman plots. The 'nomological' validity of the full tool was investigated by comparing children's brand awareness with food marketing-related variables (e.g. television habits, intake of heavily promoted foods).

Results: Brand awareness increased with age (p<0.01) but was not significantly correlated with other variables. Bland-Altman analyses showed good agreement between the ABAI and ABAI-a. Reliability analyses revealed excellent agreement between the two administrations of the full-ABAI.

Conclusions: The ABAI was able to differentiate children's varying levels of brand awareness. It was shown to be a valid and reliable tool and may allow quantification of brand awareness as a proxy measure for children's prior food marketing exposure.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0133972PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519263PMC
May 2016

Improving the participation of youth with physical disabilities in community activities: An interrupted time series design.

Aust Occup Ther J 2015 Apr 9;62(2):105-15. Epub 2015 Feb 9.

CanChild Centre for Childhood Disability Research, McMaster University, Hamilton, Ontario, Canada.

Background/aim: Youth with physical disabilities experience restrictions to participation in community-based leisure activities; however, there is little evidence about how to improve their involvement. This study examined whether an intervention to remove environmental barriers and develop strategies using a coaching approach improved youth participation in leisure activities.

Methods: An Interrupted Time Series design was employed, where replication of the intervention effect was examined across individualised participation goals and across participants. Six adolescents with a physical disability participated in a 12-week intervention. An occupational therapist worked with each youth and his/her family to set three leisure goals based on problems identified using the Canadian Occupational Performance Measure (COPM). A coaching approach was used to collaboratively identify and implement strategies to remove environmental barriers. Interventions for each goal were introduced at different time points. Outcomes were evaluated using the COPM.

Results: Improvements in COPM performance scores were clinically significant for 83% of the identified activities; an average change of 4.5 points in the performance scale (SD = 1.95) was observed. Statistical analysis using the celeration line demonstrated that the proportion of data points falling above the line increased in the intervention phase for 94% of the activities, indicating a significant treatment effect.

Conclusions: This study is the first to examine an intervention aimed at increasing leisure participation by changing only the environment. The results indicate that environment-focussed interventions are feasible and effective in promoting youth participation. Such findings can inform the design of a larger study and guide occupational therapy practice.
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http://dx.doi.org/10.1111/1440-1630.12177DOI Listing
April 2015

Age-related changes in perception of movement in driving scenes.

Ophthalmic Physiol Opt 2014 Jul 21;34(4):445-51. Epub 2014 May 21.

School of Optometry and Vision Science and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; School of Psychology and Counselling, Queensland University of Technology, Brisbane, Australia.

Purpose: Age-related changes in motion sensitivity have been found to relate to reductions in various indices of driving performance and safety. The aim of this study was to investigate the basis of this relationship in terms of determining which aspects of motion perception are most relevant to driving.

Methods: Participants included 61 regular drivers (age range 22-87 years). Visual performance was measured binocularly. Measures included visual acuity, contrast sensitivity and motion sensitivity assessed using four different approaches: (1) threshold minimum drift rate for a drifting Gabor patch, (2) Dmin from a random dot display, (3) threshold coherence from a random dot display, and (4) threshold drift rate for a second-order (contrast modulated) sinusoidal grating. Participants then completed the Hazard Perception Test (HPT) in which they were required to identify moving hazards in videos of real driving scenes, and also a Direction of Heading task (DOH) in which they identified deviations from normal lane keeping in brief videos of driving filmed from the interior of a vehicle.

Results: In bivariate correlation analyses, all motion sensitivity measures significantly declined with age. Motion coherence thresholds, and minimum drift rate threshold for the first-order stimulus (Gabor patch) both significantly predicted HPT performance even after controlling for age, visual acuity and contrast sensitivity. Bootstrap mediation analysis showed that individual differences in DOH accuracy partly explained these relationships, where those individuals with poorer motion sensitivity on the coherence and Gabor tests showed decreased ability to perceive deviations in motion in the driving videos, which related in turn to their ability to detect the moving hazards.

Conclusions: The ability to detect subtle movements in the driving environment (as determined by the DOH task) may be an important contributor to effective hazard perception, and is associated with age, and an individuals' performance on tests of motion sensitivity. The locus of the processing deficits appears to lie in first-order, rather than second-order motion pathways.
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http://dx.doi.org/10.1111/opo.12140DOI Listing
July 2014

Reliability of pedometers to measure step counts in patients with chronic respiratory disease.

J Cardiopulm Rehabil Prev 2012 Sep-Oct;32(5):284-91

Pulmonary Rehabilitation Research Group, Glenfield Hospital, University Hospitals of Leicester NHS Trust, United Kingdom.

Purpose: There are a variety of devices currently available to measure physical activity. Activity monitors are technologically advanced and provide complex data, leading to higher costs. Pedometers are simple, inexpensive devices that provide easy-to-view data. The aim of this study was to determine the reliability of pedometer step counting during slow walking speeds, typical of patients with chronic respiratory disease.

Methods: The reproducibility of 8 pedometers was initially determined at slow walking speeds in a healthy individual. Thereafter, pedometer step counting was compared with an activity monitor and visual step counts in 9 healthy subjects and 48 patients with chronic respiratory disease.

Results: Pedometers were reproducible on the same wearer, on consecutive occasions, although they were not interchangeable. During healthy subject walking, there were no significant differences between the pedometer and activity monitor at all speeds. However, both significantly undercounted steps at slower walking speeds (P < .01). At slow and medium walking speeds with patients with chronic respiratory disease, both the pedometer and activity monitor significantly undercounted steps (P < .001 for both pedometer and activity monitor at slow and P < .003 for pedometer and P < .004 for activity monitor at medium speeds) compared with visual counts.

Conclusions: Pedometers are an inexpensive and simple alternative to activity monitors and appear to be reliable during faster walking in both healthy subjects and patients with chronic respiratory disease. However, caution should be applied during slow walking speeds because of undercounting steps, causing misleading data that could become demotivating when used as a training adjunct.
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http://dx.doi.org/10.1097/HCR.0b013e31825c49f2DOI Listing
January 2013

The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset.

Nature 2011 Mar;471(7339):513-7

Stem Cell Program and Hematology/Oncology, Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway. BRAF(V600E) mutations are also present in benign melanocytic naevi, highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes. For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis.
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http://dx.doi.org/10.1038/nature09806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348545PMC
March 2011

Inappropriate measures of population health for parasitic disease?

Trends Parasitol 2009 Sep 31;25(9):393-5. Epub 2009 Aug 31.

School of Biological Sciences, University of Bristol, Woodland Road, Bristol, BS8 1UG, UK.

The dominant metric for setting public health priorities, the disability-adjusted life year (DALY), is unsuited to parasitic infections. In particular, the current DALY framework fails to acknowledge the non-linear pathologies of infection, the community level dynamics of epidemiology and the co-morbidities of polyparasitism. Parasitologists must urgently provide a better way of accounting for the true costs of parasitic disease.
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http://dx.doi.org/10.1016/j.pt.2009.05.013DOI Listing
September 2009

Effects of the physico-chemical nature of two biomimetic crystals on the innate immune response.

Int Immunopharmacol 2007 Dec 4;7(13):1617-29. Epub 2007 Sep 4.

Department of Immunology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, Connecticut 06030, USA.

The influence of the physico-chemical features of particulates made of calcium phosphate (hydroxyapatite, HAP) crystals, or monosodium urate monohydrate (MSUM) crystals, on the innate immune response was investigated in mice after intraperitoneal injections. The phenotype and activation status of harvested peritoneal cells from C57BL/6 mice was determined by flow cytometry analysis at 24, 48 and 72 h after particulate injections and compared to a known adjuvant, aluminum phosphate (ALP). A rigorous characterization of the chemistry, structure, morphology and particle size of the particulates was completed. Mid-sized (10 mum mean size) particulates of both crystal types recruited the most cells, as compared to fine (1 mum) or large (100 mum) particulates. Analysis of sub-populations of the peritoneal cells revealed that MSUM induced fewer PMNs and eosinophils than HAP or ALP. MSUM also had the greatest effect on the expression of CD11b, MHC-Class II and CD86 on peritoneal macrophages indicating MSUM provides a robust antigen presenting and co-stimulatory bridge between the innate and adaptive immune systems. This study indicates that manipulation of the physico-chemical features of particulates is a means of controlling the innate immune response and that knife-like morphologies are more stimulatory than spherical or plate-like shapes. Proper utilization of the physico-chemical features of particulates offers a new direction for the development of more effective vaccine adjuvants.
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http://dx.doi.org/10.1016/j.intimp.2007.08.011DOI Listing
December 2007

Short-term social recognition memory deficit and atypical social and physiological stressor reactivity in seizure-susceptible El mice.

Seizure 2007 Jan 20;16(1):59-68. Epub 2006 Nov 20.

Department of Psychology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.

The present studies characterize working memory capabilities in the El mouse model of epilepsy using a species-typical social recognition memory task. As the El mouse exhibits a stress hyper-reactivity phenotype, the impact of hypertonic saline consumption, a memory modulatory treatment, upon social recognition performance was also examined. The hypotheses under test were: (1) that seizure susceptible El mice would perform poorly in the short-term working memory task relative to seizure resistant ddY controls, and (2) that the behavioral and neural responses to stressor exposure would be atypical in El mice. Results revealed a short-term working memory deficit and altered reactivity to social, environmental, and physiological stressors in El mice. In Experiment 1, El mice exhibited poor sociability and decreased olfactory investigation times, both anxiogenic-like traits, compared to ddY controls. In Experiment 2, El mice exhibited poor working memory performance compared to capable performance in ddY controls. Social recognition memory in ddY mice was abolished, however, by salt-loading whereas El mice were unaffected by exposure to this physiological stressor. In Experiment 3, all salt-loaded mice exhibited enhanced brain stress neuropeptide (corticotropin releasing factor-CRF) content, and salt-loaded El mice exhibited a 70% reduction in handling-induced seizures. These findings suggest that El mice exhibit high emotionality as well as atypical reactions to stressor exposure, and that these characteristics impact social working memory performance and seizure susceptibility.
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http://dx.doi.org/10.1016/j.seizure.2006.10.006DOI Listing
January 2007

Antisocial and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin-releasing factor.

Epilepsy Behav 2007 Feb 4;10(1):8-15. Epub 2006 Oct 4.

Department of Psychology, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA.

Social interaction phenotyping is an unexplored niche in animal modeling of epilepsy despite the sensitivity of affiliative behaviors to emotionality and stress, which are known seizure triggers. Thus, the present studies examined the social phenotype of seizure-susceptible El and nonsusceptible ddY strains both in untreated animals and following preexposure to a handling stressor. The second aim of the present studies was to evaluate the dependence of sociability in El mice on the proconvulsive, stress neuropeptide corticotropin-releasing factor (CRF) using CRF-SAP, a conjugate of CRF and the toxin saporin, which selectively reduced CRF peptide levels in the basolateral amygdala of El mice. El mice exhibited lower social investigation times than ddY counterparts, whereas central administration of CRF-SAP normalized social investigation times relative to ddY controls. Moreover, handling-induced seizures in El mice were reduced by 50% following treatment with CRF-SAP relative to saporin alone-injected El controls. The results of this study suggest that tonically activated CRF systems in the El mouse brain suppress affiliative behavior and facilitate evoked seizures.
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http://dx.doi.org/10.1016/j.yebeh.2006.08.013DOI Listing
February 2007

Plexin-induced collapse assay in COS cells.

Methods Enzymol 2006 ;406:665-76

Eisai London Research Laboratories, University College London, UK.

Semaphorins are a family of growth cone guidance molecules. When associated with their receptors and coreceptors, plexins and neuropilins, they act as chemorepellents for an extensive range of neuronal populations. The prototypic semaphorin, Sema3A, has a potent inhibitory effect on sensory axons emanating from dorsal root ganglia. This has formed the basis of the most famous assay for semaphorin activity, the chick dorsal root ganglia collapse assay. Recently, a heterologous, highly tractable assay has been used to investigate semaphorin signaling. In this system, the binding of recombinant semaphorins to COS cells expressing plexins and neuropilins induces a morphological collapse that may correlate with growth cone collapse. This chapter describes the optimization of this assay and outlines the subtle differences required to enable Sema3A-Fc and Sema4D-Fc to induce identical collapse phenotypes in COS cells expressing Plexin-A1 and neuropilin-1, or Plexin-B1, respectively.
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http://dx.doi.org/10.1016/S0076-6879(06)06052-6DOI Listing
March 2006

The activity of the plexin-A1 receptor is regulated by Rac.

J Biol Chem 2004 Aug 8;279(32):33199-205. Epub 2004 Jun 8.

MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, Department of Biochemistry and Molecular Biology, Cancer Research UK, Oncogene and Signal Transduction Group, University College London, Gower Street, London, WC1E 6BT, United Kingdom.

Plexins constitute a large family of transmembrane proteins that act as receptors for the semaphorin family of ligands. They are best known for their role in growth cone guidance, although they also are widely expressed outside the nervous system. Plexins are thought to control axon guidance by modifying the growth cone cytoskeleton, and Rho GTPases have been strongly implicated in this response. However, the exact contribution of Rho proteins is unclear. Sema3A/Plexin-A1-induced growth cone collapse, for example, requires Rac activity, which is a surprising result given that this GTPase is usually associated with membrane protrusions. We show here that Sema3A-induced collapse of COS-7 cells expressing Plexin-A1 also requires Rac but not Rho activity and that the cytoplasmic tail of Plexin-A1 interacts directly with activated Rac. However, collapse induced by a constitutively activated version of Plexin-A1 does not require Rac. We propose a novel function for Rac, namely that it acts upstream of Plexin-A1 during semaphoring-induced collapse, to regulate the activity of the receptor.
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http://dx.doi.org/10.1074/jbc.M402943200DOI Listing
August 2004

Building the foundations of wound care training: the need to fight the mantra "time is money".

Home Healthc Nurse 2004 May;22(5):304-11

BestCare Home Health Agency, Fresno, CA, USA.

The home care wound patient is continuing to grow and requires a significant organizational commitment to keep field staff current. One agency's successful effort to develop a wound management program is presented.
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http://dx.doi.org/10.1097/00004045-200405000-00007DOI Listing
May 2004

Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp. I. Taxonomy, fermentation and biological activities.

J Antibiot (Tokyo) 2003 Mar;56(3):226-31

Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA.

Thiazolyl peptide antibiotics, nocathiacin I, II and III, were identified in a culture of Nocardia sp. WW-12651 (ATCC 202099). They exhibit potent in vitro activity (ng/ml) against a wide spectrum of gram-positive bacteria, including multiple-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Enterococcus faecium (MREF) and fully penicillin-resistant Streptococcus pneumoniae (PRSP), and demonstrate excellent in vivo efficacy in a systemic Staphylococcus aureus infection mice model.
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http://dx.doi.org/10.7164/antibiotics.56.226DOI Listing
March 2003

Dynamic analysis of actin cable function during Drosophila dorsal closure.

Curr Biol 2002 Jul;12(14):1245-50

Department of Anatomy andDevelopmental Biology, University College London, United Kingdom.

Throughout development, a series of epithelial movements and fusions occur that collectively shape the embryo. They are dependent on coordinated reorganizations and contractions of the actin cytoskeleton within defined populations of epithelial cells. One paradigm morphogenetic movement, dorsal closure in the Drosophila embryo, involves closure of a dorsal epithelial hole by sweeping of epithelium from the two sides of the embryo over the exposed extraembryonic amnioserosa to form a seam where the two epithelial edges fuse together. The front row cells exhibit a thick actin cable at their leading edge. Here, we test the function of this cable by live analysis of GFP-actin-expressing embryos in which the cable is disrupted by modulating Rho1 signaling or by loss of non-muscle myosin (Zipper) function. We show that the cable serves a dual role during dorsal closure. It is contractile and thus can operate as a "purse string," but it also restricts forward movement of the leading edge and excess activity of filopodia/lamellipodia. Stripes of epithelium in which cable assembly is disrupted gain a migrational advantage over their wild-type neighbors, suggesting that the cable acts to restrain front row cells, thus maintaining a taut, free edge for efficient zippering together of the epithelial sheets.
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http://dx.doi.org/10.1016/s0960-9822(02)00955-7DOI Listing
July 2002
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