Development of a universal approach to increase physical activity among adolescents: the GoActive intervention.

OBJECTIVES: To develop a physical activity (PA) promotion intervention for adolescents using a process addressing gaps in the literature while considering participant engagement. We describe the initial development stages; (1) existing evidence, (2) large scale opinion gathering and (3) developmental qualitative work, aiming (A) to gain insight into how to increase PA among the whole of year 9 (13-14 years-old) by identifying elements for intervention inclusion (B) to improve participant engagement and (C) to develop and refine programme design. METHODS: Relevant systematic reviews and longitudinal analyses of change were examined. An intervention was developed iteratively with older adolescents (17.3 ± 0.5 years) and teachers, using the following process: (1) focus groups with (A) adolescents (n=26) and (B) teachers (n=4); (2) individual interviews (n=5) with inactive and shy adolescents focusing on engagement and programme acceptability. Qualitative data were analysed thematically. RESULTS: Limitations of the existing literature include lack of evidence on whole population approaches, limited adolescent involvement in intervention development, and poor participant engagement. Qualitative work suggested six themes which may encourage adolescents to do more PA; choice, novelty, mentorship, competition, rewards and flexibility. Teachers discussed time pressures as a barrier to encouraging adolescent PA and suggested between-class competition as a strategy. GoActive aims to increase PA through increased peer support, self-efficacy, group cohesion, self-esteem and friendship quality, and is implemented in tutor groups using a student-led tiered-leadership system. CONCLUSIONS: We have followed an evidence-based iterative approach to translate existing evidence into an adolescent PA promotion intervention. Qualitative work with adolescents and teachers supported intervention design and addressed lack of engagement with health promotion programmes within this age group. Future work will examine the feasibility and effectiveness of GoActive to increase PA among adolescents while monitoring potential negative effects. The approach developed is applicable to other population groups and health behaviours. TRIAL REGISTRATION NUMBER: ISRCTN31583496.Funding for this development study and the work of all authors was supported, wholly or in part, by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence (RES 590 28 0002). Funding from the British Heart Foundation, Department of Health, Economic and Social Research Council, Medical Research Council, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The work of Kirsten Corder, Joanna Kesten and Esther M F van Sluijs was supported by the Medical Research Council (MC_UU_ 12015/7 and MC_UU_12015/6).This is the final version of the article. It first appeared from the BMJ Publishing Group via http://dx.doi.org/10.1136/bmjopen-2015-00861

Quasi-normal frequencies: Key analytic results

The study of exact quasi-normal modes [QNMs], and their associated quasi-normal frequencies [QNFs], has had a long and convoluted history - replete with many rediscoveries of previously known results. In this article we shall collect and survey a number of known analytic results, and develop several new analytic results - specifically we shall provide several new QNF results and estimates, in a form amenable for comparison with the extant literature. Apart from their intrinsic interest, these exact and approximate results serve as a backdrop and a consistency check on ongoing efforts to find general model-independent estimates for QNFs, and general model-independent bounds on transmission probabilities. Our calculations also provide yet another physics application of the Lambert W function. These ideas have relevance to fields as diverse as black hole physics, (where they are related to the damped oscillations of astrophysical black holes, to greybody factors for the Hawking radiation, and to more speculative state-counting models for the Bekenstein entropy), to quantum field theory (where they are related to Casimir energies in unbounded systems), through to condensed matter physics, (where one may literally be interested in an electron tunelling through a physical barrier).Comment: V1: 29 pages; V2: Reformatted, 31 pages. Title changed to reflect major additions and revisions. Now describes exact QNFs for the double-delta potential in terms of the Lambert W function. V3: Minor edits for clarity. Four references added. No physics changes. Still 31 page

A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models.

Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of severe combined immunodeficient (SCID)/Beige and nonobese diabetic (NOD)/SCID/IL-2γ-receptor null (NSG) mice under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (∼21% and ∼19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing 25 unique patients. Most tumors yielding xenografts were "triple-negative" [estrogen receptor (ER)-progesterone receptor (PR)-HER2+; n = 19]. However, we established lines from 3 ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2-, and one "triple-positive" (ER+PR+HER2+) tumor. Serially passaged xenografts show biologic consistency with the tumor of origin, are phenotypically stable across multiple transplant generations at the histologic, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses as those observed clinically. Xenografts representing 12 patients, including 2 ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis

A model of feedback control for the charge-balanced suppression of epileptic seizures

Here we present several refinements to a model of feedback control for the suppression of epileptic seizures. We utilize a stochastic partial differential equation (SPDE) model of the human cortex. First, we verify the strong convergence of numerical solutions to this model, paying special attention to the sharp spatial changes that occur at electrode edges. This allows us to choose appropriate step sizes for our simulations; because the spatial step size must be small relative to the size of an electrode in order to resolve its electrical behavior, we are able to include a more detailed electrode profile in the simulation. Then, based on evidence that the mean soma potential is not the variable most closely related to the measurement of a cortical surface electrode, we develop a new model for this. The model is based on the currents flowing in the cortex and is used for a simulation of feedback control. The simulation utilizes a new control algorithm incorporating the total integral of the applied electrical potential. Not only does this succeed in suppressing the seizure-like oscillations, but it guarantees that the applied signal will be charge-balanced and therefore unlikely to cause cortical damage

Impact of seasonal variation, age and smoking status on human semen parameters: The Massachusetts General Hospital experience

BACKGROUND: To investigate the relationship of human semen parameters with season, age and smoking status. METHODS: The present study used data from subjects recruited into an ongoing cross-sectional study on the relationship between environmental agents and semen characteristics. Our population consisted of 306 patients who presented to the Vincent Memorial Andrology Laboratory of Massachusetts General Hospital for semen evaluation. Sperm concentration and motility were measured with computer aided sperm analysis (CASA). Sperm morphology was scored using Tygerberg Kruger strict criteria. Regression analyses were used to investigate the relationships between semen parameters and season, age and smoking status, adjusting for abstinence interval. RESULTS: Sperm concentration in the spring was significantly higher than in winter, fall and summer (p < 0.05). There was suggestive evidence of higher sperm motility and percent of sperm with normal morphology in the spring than in the other seasons. There were no statistically significant relationships between semen parameters and smoking status, though current smokers tended to have lower sperm concentration. We also did not find a statistically significant relationship between age and semen parameters. CONCLUSIONS: We found seasonal variations in sperm concentration and suggestive evidence of seasonal variation in sperm motility and percent sperm with normal morphology. Although smoking status was not a significant predictor of semen parameters, this may have been due to the small number of current smokers in the study

Current Antiviral Therapy of Chronic Hepatitis B: Efficacy and Safety

The treatment of chronic hepatitis B is in constant evolution. Interferon, the first agent licensed for chronic hepatitis B treatment, has been superseded by the growing popularity of nucleoside/nucleotide analogues (NA). However, resistance to these agents is a major challenge. Newer NAs, such as entecavir and tenofovir dipivoxil fumarate, have very low resistance rates and favorable safety profiles. Long-term use of these agents can effectively suppress hepatitis B virus DNA, leading to decrease in incidence of hepatitic flares, as well as in the development of cirrhosis and hepatocellular carcinoma. The efficacy and safety of various antiviral agents is discussed in this review

Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours

BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)α (cPLA(2)α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)α expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)α activity in clinical breast cancer was established by relating the expression of cPLA(2)α in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)α mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)α expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)α expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)α in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker

Routine human papillomavirus genotyping by DNA sequencing in community hospital laboratories

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) genotyping is important for following up patients with persistent HPV infection and for evaluation of prevention strategy for the individual patients to be immunized with type-specific HPV vaccines. The aim of this study was to optimize a robust "low-temperature" (LoTemp™) PCR system to streamline the research protocols for HPV DNA nested PCR-amplification followed by genotyping with direct DNA sequencing. The protocol optimization facilitates transferring this molecular technology into clinical laboratory practice. In particular, lowering the temperature by 10°C at each step of thermocycling during <it>in vitro </it>DNA amplification yields more homogeneous PCR products. With this protocol, template purification before enzymatic cycle primer extensions is no longer necessary.</p> <p>Results</p> <p>The HPV genomic DNA extracted from liquid-based alcohol-preserved cervicovaginal cells was first amplified by the consensus MY09/MY11 primer pair followed by nested PCR with GP5+/GP6+ primers. The 150 bp nested PCR products were subjected to direct DNA sequencing. The hypervariable 34–50 bp DNA sequence downstream of the GP5+ primer site was compared to the known HPV DNA sequences stored in the GenBank using on-line BLAST for genotyping. The LoTemp™ ready-to-use PCR polymerase reagents proved to be stable at room temperature for at least 6 weeks. Nested PCR detected 107 isolates of HPV in 513 cervicovaginal clinical samples, all validated by DNA sequencing. HPV-16 was the most prevalent genotype constituting 29 of 107 positive cases (27.2%), followed by HPV-56 (8.5%). For comparison, Digene HC2 test detected 62.6% of the 107 HPV isolates and returned 11 (37.9%) of the 29 HPV-16 positive cases as "positive for high-risk HPV".</p> <p>Conclusion</p> <p>The LoTemp™ ready-to-use PCR polymerase system which allows thermocycling at 85°C for denaturing, 40°C for annealing and 65°C for primer extension can be adapted for target HPV DNA amplification by nested PCR and for preparation of clinical materials for genotyping by direct DNA sequencing. HPV genotyping is performed by on-line BLAST algorithm of a hypervariable L1 region. The DNA sequence is included in each report to the physician for comparison in following up patients with persistent HPV infection, a recognized tumor promoter in cancer induction.</p