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Latest Paper:
Centre for Water Systems, University of Exeter, North Park Road, Exeter EX4 4QF, UK E-mail: sw278@exeter.ac.uk; d.butler@exeter.ac.uk; f.a.memon@exeter.ac.uk.
Numerous policy vehicles have been introduced in the UK promoting the use of rainwater harvesting (RWH). However, an 'implementation deficit' exists where legislation limits action by failing to provide adequate support mechanisms. This study uses an interdisciplinary approach to construct a framework to address the issue of overcoming this deficit. Evidence bases have identified six deficit categories, which confirm a lack of enabling of stakeholders. Outline recommendations, such as coordinated information provision and reconsideration of incentive schemes are made in relation to these categories to complete the framework for supporting RWH in the UK.
1Gramercy Research Group, Winston Salem, NC; 2University of Illinois at Urbana-Champaign, Department of Kinesiology and Community Health, Champaign, IL; 3University of Kansas, Department of Applied Behavioral Science, Lawrence, KS; 4Department of Health, Physical Education, and Exercise Science, Norfolk State University, Norfolk, VA; 5College of William & Mary, Department of Kinesiology & Health Sciences, Williamsburg, VA.
The benefits of physical activity on diseases and risk factors are well known. Despite the known benefits, many segments of the population, particularly African-American women and girls, do not obtain adequate levels of physical activity. Strategies are needed to identify successful and sustainable interventions to increase physical activity among this population. We reviewed literature published between 2007 and 2009 that focused on increasing physical activity or fitness among this population. We identified 37 studies, 11 of which focused on increasing physical activity. This article summarizes the findings from those 11 studies and provides recommendations for improving strategies to increase physical activity in African-American women and girls.
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, Pennsylvania, USA.
Both cannabinoid CB1 receptor knockout and antagonism produce well-established attenuation of palatable food and drug self-administration behavior. Although cannabinoid drugs have received attention as pharmacotherapeutics for various disorders, including obesity and addiction, it is unclear whether these agents produce equivalent behavioral effects in females and males. In this study, acquisition of 32% corn oil or 10% Ensure self-administration, and maintenance of corn oil, Ensure, or .56 mg/kg/infusion cocaine self-administration under both fixed ratio (FR)-1 and progressive ratio (PR) schedule of reinforcement, was compared in male and female wild type (WT) and CB1 knockout (KO) mice. Furthermore, the effect of pretreatment with the CB1 antagonist SR141716 ( .3-3. ) on Ensure self-administration in male and female WT and CB1 KO mice was assessed. CB1 genotype and sex significantly interacted to produce an attenuation of acquisition and maintenance of Ensure self-administration and PR self-administration for both Ensure and cocaine in male CB1 KO mice. In contrast, male CB1 KO mice showed no deficit in acquisition and maintenance of FR-1 responding or in PR responding maintained by corn oil. Sex differences also arose within genotypes for responding maintained under all three reinforcers. Lastly, pretreatment with SR141716 attenuated Ensure self-administration in WT and CB1 KO mice but was approximately five-fold more potent in WT mice than in CB1 KOs. The present data add to a small but growing literature suggesting that the cannabinoid system may be differentially sensitive in its modulation of appetitive behavior in males versus females.
A B Del Campo,
N Aptsiauri,
R Méndez,
S Zinchenko,
A Vales,
A Paschen,
S Ward,
F Ruiz-Cabello,
G González-Aseguinolaza,
F Garrido
Departamento de Análisis Clínicos, Hospital Universitario Virgen de las Nieves, Granada.
Here we report a successful use of a non-replicating adenovirus expressing the wild-type human beta2m gene in recovery of normal human leucocyte antigen (HLA) class I expression in beta2m-null cancer cells. Total loss of HLA class I expression in these cell lines is caused by a mutation in beta2m gene and a loss of heterozygosity in chromosome 15 carrying another copy of that gene. Normal HLA class I expression on the tumour cell surface is critical for the successful outcome of cancer immunotherapy as T cells can only recognize tumour-derived peptides in a complex with self-HLA class I molecules. In this report we characterize the newly generated adenoviral vector AdCMVbeta2m and demonstrate an efficient beta2m gene transfer in tumour cell lines of different histological origin, including melanoma, prostate and colorectal carcinoma. The beta2m re-expression lasted for an extended period of time both in vitro and in vivo in human tumour xenograft transplants. We propose that in a subset of cancer patients with structural defect in beta2m gene or chromosome 15, the adenoviral-mediated recovery (or even increase) of HLA class I expression on tumour cells in combination with vaccination or adoptive T-cell therapy can provide a complementary approach to improve the clinical efficacy of cancer immunotherapy.
Lucas Smith,
Eva Ponten,
Yvette Hedstrom,
Samuel Ward,
Henry Chambers,
Shankar Subramaniam,
Richard Lieber
ABSTRACT: BACKGROUND: Cerebral palsy (CP) is an upper motor neuron disease that results in a progressive movement disorder. Secondary to the neurological insult, muscles from CP patients often become spastic. Spastic muscle is characterized by an increased resistance to stretch, but often develops the further complication of contracture which represents a prominent disability in children with CP. This study's purpose is to characterize alterations of spastic muscle on the transcriptional level. Increased knowledge of spastic muscle may lead to novel therapies to improve the quality of life for children with CP. METHOD: The transcriptional profile of spastic muscles were defined in children with cerebral palsy and compared to control patients using Affymetrix U133A chips. Expression data were verified using quantitative-PCR (QPCR) and validated with SDS-PAGE for select genes. Significant genes were determined using a 2x2 ANOVA and results required congruence between 3 preprocessing algorithms. RESULTS: CP patients clustered independently and 205 genes were significantly altered, covering a range of cellular processes. Placing gene expression in the context of physiological pathways, the results demonstrated that spastic muscle in CP adapts transcriptionally by altering extracellular matrix, fiber type, and myogenic potential. Extracellular matrix adaptations occur primarily in the basal lamina although there is increase in fibrillar collagen components. Fiber type is predominately fast compared to normal muscle as evidenced by contractile gene isoforms and decrease in oxidative metabolic gene transcription, despite a paradoxical increased transcription of slow fiber pathway genes. We also found competing pathways of fiber hypertrophy with an increase in the anabolic IGF1 gene in parallel with a paradoxical increase in myostatin, a gene responsible for stopping muscle growth. We found evidence that excitation-contraction coupling genes are altered in muscles from patients with CP and may be a significant component of disease. CONCLUSIONS: This is the first transcriptional profile performed on spastic muscle of CP patients and these adaptations were not characteristic of those observed in other disease states such as Duchenne muscular dystrophy and immobilization-induced muscle atrophy. Further research is required to understand the mechanism of muscle adaptation to this upper motor neuron lesion that could lead to the development of innovative therapies.
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA, 19140, USA, saraward@temple.edu.
RATIONALE: The cannabinoid CB1 selective antagonist SR141716A (Rimonabant) has been shown to decrease body weight in laboratory animals and humans. Furthermore, SR141716A can elicit scratching behavior in rodents, a behavior that has been hypothesized to contribute to SR141716A-induced decrease in food intake. Although childhood obesity is a rising health issue, it is unknown whether SR141716A is equipotent at modulating food intake and other CB1-mediated behaviors in younger subjects. OBJECTIVE: To determine whether CB1 receptor blockade is equipotent at modulating food and water intake, body weight, and scratching behavior, the effect of a range of SR141716A doses on these behaviors in food-restricted postnatal day (P) 18, 28, and 60 male rats was investigated. Brain concentrations of SR141716A were determined in each age group. RESULTS: SR141716A dose- and age-dependently suppressed food and water intake and body weight gain and elicited head scratching, with the most potent effects observed in P18 and P28 rats. Brain concentrations of SR141716A were significantly elevated in P18 rats relative to P28 and P60 rats. SR141716A-elicited head scratching was attenuated by the 5-HT(2A/2C) antagonist ketanserin. CONCLUSIONS: SR141716A is more potent at modulating food intake and head scratching in very young animals; these differences can be attributed to an increase in brain penetration of SR141716A for P18 but not for P28 and P60 rats. In addition, SR141716-elicited head scratching is modulated by 5HT receptor antagonism and is not a contributing factor to SR141716A's anorectic effects.
School of Health and Related Research (ScHARR), University of Sheffield, UK. s.e.ward@sheffield.ac.uk
This paper presents a summary of the evidence review group (ERG) report into the the clinical and cost-effectiveness of trastuzumab for the treatment of primary breast cancer in human epidermal growth factor 2 (HER2)-positive women based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer's scope restricts the intervention to intravenous trastuzumab given for 1 year after surgery and after the completion of standard adjuvant chemotherapy, and the comparator to standard therapy without trastuzumab. The clinical rationale for the duration of treatment in the scope is open to question and leads to the exclsuion of one potentially relevant trial. The submitted evidence reports that the 3-weekly regimen of trastuzumab produced a relative reduction in all-cause mortality of 24-33%. Meta-analysis of all available studies based on 12 months of trastuzumab showed that there was a statistically significant 30% relative improvement in overall survival using the 3-weekly regimen. A study looking at weekly cycles of trastuzumab, excluded in the manufacturer's submission, produced a relative reduction in all-cause mortality of 59%, which was not statistically significant. All included studies showed a statistically significant difference in the risk of recurrence or death from any cause (disease-free survival), favouring trastuzumab. There was a statistically significant increase in the relative risk of a serious adverse event in women treated with 3-weekly cycles of trastuzumab, with no excess toxicity in the study evaluating weekly cycles. Estimates of cost-effectiveness provided by the manufacturer were based on data from the HERA trial using the 3-weekly regimen of trastuzumab. The economic model was a state-transition model that compared the lifetime impact of adding 1 year of trastuzumab therapy to standard care with standard care alone. The initial cost-effectiveness estimate was 5687 pounds per additional quality-adjusted life-year (QALY) gained, rising to a maximum of 8689 pounds upon one-way sensitivity analysis. The base-case estimate of cost-effectiveness was subsequently revised by the manufacturer, resulting in an estimated incremental cost per additional QALY gained of 2387 pounds. A number of assumptions behind the manufacturer's model may be optimistic and could mean that the incremental costs per QALY gained were underestimated. Additional analysis carried out by the evidence review group concluded that the incremental cost-effectiveness ratio (ICER) is expected to be around 20,000 pounds to 30,000 pounds. The addition of potential long-term cardiac events could push the ICER above 30,000 pounds, although there is no long-term evidence to date surrounding this issue. In addition, the small study excluded from the manufacturer's submission raises the possibility of an equally effective but shorter regimen, incurring lower cost and toxicity and with greater patient convenience. The guidance issued by NICE in June 2006 as a result of the STA states that trastuzumab, given at 3-week intervals for 1 year or until disease recurrence, is recommended as a treatment option for women with early-stage HER2-positive breast cancer following surgery, chemotherapy and radiotherapy.
University of New Hampshire.
Since sexual assault survivors are most likely to disclose their experiences to a friend; prevention efforts increasingly focus on friends as informal helpers. The current study examined friends' perceptions of the disclosure experience. Undergraduates (N=1,241) at the University of New Hampshire completed a shortened version of the Ahrens and Campbell (2000) Impact on Friends measure. Results found that about 1 in 3 female undergraduates and 1 in 5 male students were told by a friend that they were a victim of an unwanted sexual experience. Gender differences were found in friends' responses to disclosure. Women reported greater emotional distress in response to a friend's disclosure, greater positive responses and lesser-perceived confusion/ineffectiveness as compared to men. Implications include the need to develop specific and clear educational material to help the community cope with and effectively respond to unwanted sexual experiences on college campuses.
Upper Gastrointestinal Surgery Unit, Alfred Hospital, Commercial Road, Prahran, Victoria, Australia, 3181, charlespilgrim@hotmail.com.
INTRODUCTION: Development of gallbladder cancer following cholecystojejunostomy has not previously been described. METHODS: A case of a patient who developed gallbladder cancer 22 years following cholecystojejunostomy is presented, and a literature review of known complications of cholecysto-enteric anastomosis was performed. DISCUSSION: Cholangitis is the commonest reported complication, known to predispose the biliary epithelium to malignant change, but has not been described until now as being carcinogenic for the gallbladder. Gallbladder carcinoma may be a rare long-term complication of cholecystojejunostomy.
A Brent Richards,
Richard W Morris,
Sarah Ward,
Stephanie Schmitz,
Debora A Rothmond,
Pam L Noble,
Ruth A Woodward,
James T Winslow,
Cynthia Shannon Weickert
MiNDS Unit, NIMH, Bethesda, MD.
Social behavior changes dramatically during primate adolescence. However, the extent to which testosterone and other gonadal hormones are necessary for adolescent social behavioral development is unknown. In this study, we determined that gonadectomy significantly impairs social dominance in naturalistic settings and changes reactions to social stimuli in experimental settings. Rhesus macaques were castrated (n = 6) or sham operated (n = 6) at age 2.4 years, group-housed for 2 years, and ethograms were collected weekly. During adolescence the gonadally intact monkeys displayed a decrease in subordinate behaviors and an increase in dominant behaviors, which ultimately related to a rise in social status and rank in the dominance hierarchy. We measured monkey's reactions to emotional faces (fear, threat, neutral) of conspecifics of three ages (adult, peer, infant). Intact monkeys were faster to retrieve a treat in front of a threatening or infant face, while castrated monkeys did not show a differential response to different emotional faces or ages. No group difference in reaction to an innate fear-eliciting object (snake) was found. Approach and proximity responses to familiar versus unfamiliar conspecifics were tested, and intact monkeys spent more time proximal to a novel conspecific as compared to castrates who tended to spend more time with a familiar conspecific. No group differences in time spent with novel or familiar objects were found. Thus, gonadectomy resulted in the emergence of significantly different responses to social stimuli, but not non-social stimuli. Our work suggests that intact gonads, which are needed to produce adolescent increases in circulating testosterone, impact social behavior during adolescences in primates.
