Experiences of a commercial weight-loss programme after primary care referral: a qualitative study.

BACKGROUND: Referral to a commercial weight-loss programme is a cost-effective intervention that is already used within the NHS. Qualitative research suggests this community-based, non-medical intervention accords with participants' view of weight management as a lifestyle issue. AIM: To examine the ways in which participants' attitudes and beliefs about accessing a commercial weight management programme via their doctor relate to their weight-loss experience, and to understand how these contextual factors influence motivation and adherence to the intervention. DESIGN AND SETTING: A qualitative study embedded in a randomised controlled trial evaluating primary care referral to a commercial weight-loss programme in adults who are overweight or obese in England. The study took place from June-September 2013. METHOD: Twenty-nine participants (body mass index [BMI] ≥28 kg/m(2); age ≥18 years), who took part in the WRAP (Weight Loss Referrals for Adults in Primary Care) trial, were recruited at their 3-month assessment appointment to participate in a semi-structured interview about their experience of the intervention and weight management more generally. Interviews were audiorecorded, transcribed verbatim, and analysed inductively using a narrative approach. RESULTS: Although participants view the lifestyle-based, non-medical commercial programme as an appropriate intervention for weight management, the referral from the GP and subsequent clinical assessments frame their experience of the intervention as medically pertinent with clear health benefits. CONCLUSION: Referral by the GP and follow-up assessment appointments were integral to participant experiences of the intervention, and could be adapted for use in general practice potentially to augment treatment effects

Large Scale Reasoning Using Allen's Interval Algebra

This paper proposes and evaluates a distributed, parallel approach for reasoning over large scale datasets using Allen's Interval Algebra (IA). We have developed and implemented algorithms that reason over IA networks using the Spark distributed processing framework. Experiments have been conducted by deploying the algorithms on computer clusters using synthetic datasets with various characteristics. We show that reasoning over datasets consisting of millions of interval relations is feasible and that our implementation scales effectively. The size of the IA networks we are able to reason over is far greater than those found in previously published works

Primordial Gravitational Waves From Open Inflation

We calculate the spectrum of gravitational waves generated during inflation in open $(\Omega _0<1)$ inflationary models. In such models an initial epoch of old inflation solves the horizon and flatness problems, and during this first epoch of inflation the quantum state of the graviton field rapidly approaches the Bunch-Davies vacuum. Then old inflation ends by the nucleation of a single bubble, inside of which there is a shortened epoch of slow-roll inflation giving $\Omega _0<1$ today. In this paper we re-express the Bunch-Davies vacuum for the graviton field in terms of the hyperbolic modes inside the bubble and propagate these modes forward in time into the present era. We derive the expression for the contribution from these gravity waves to the cosmic microwave background anisotropy including the effect of a finite energy difference across the bubble wall.Comment: 40 pages, TEX with phyzzx macro, 5 figure

Asymptotic behaviour of random tridiagonal Markov chains in biological applications

Discrete-time discrete-state random Markov chains with a tridiagonal generator are shown to have a random attractor consisting of singleton subsets, essentially a random path, in the simplex of probability vectors. The proof uses the Hilbert projection metric and the fact that the linear cocycle generated by the Markov chain is a uniformly contractive mapping of the positive cone into itself. The proof does not involve probabilistic properties of the sample path and is thus equally valid in the nonautonomous deterministic context of Markov chains with, say, periodically varying transitions probabilities, in which case the attractor is a periodic path.Comment: 13 pages, 22 bibliography references, submitted to DCDS-B, added references and minor correction

Quasiparticle contribution to heat carriers relaxation time in DyBa2_2Cu3_3O7−x_{7-x} from heat diffusivity measurements

It is shown that the controversy on phonons or electrons being the most influenced heat carriers below the critical temperature of high-T$_c$ superconductors can be resolved. Electrical and thermal properties of the same DyBa$_2$Cu$_3$O$_{7-x}$ monodomain have been measured for two highly different oxygenation levels. While the oxygenated sample DyBa$_2$Cu$_3$O$_{7}$ has very good superconducting properties ($T_c=90$ K), the DyBa$_2$Cu$_3$O$_{6.3}$ sample exhibits an insulator behavior. A careful comparison between measurements of the {\bf thermal diffusivity} of both samples allows us to extract the electronic contribution. This contribution to the relaxation time of heat carriers is shown to be large below $T_c$ and more sensitive to the superconducting state than the phonon contribution.Comment: 13 pages, 6 figure

Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 362

Drug and alcohol use have been associated with a worse prognosis in short-term and cross-sectional analyses of HIV-infected populations, but longitudinal effects on adherence to antiretroviral therapy (ART) and clinical outcomes in advanced AIDS are less well characterized. We assessed self-reported drug and alcohol use in AIDS patients, and examined their association with non-adherence and death or disease progression in a multicenter observational study. We defined non-adherence as reporting missed ART doses in the 48 hours before study visits. The association between drug use and ART non-adherence was evaluated using repeated measures generalized estimating equation (GEE) models. The association between drug and alcohol use and time to new AIDS diagnosis or death was evaluated via Cox regression models, controlling for covariates including ART adherence. Of 643 participants enrolled between 1997–1999 and followed through 2007, at entry 39% reported ever using cocaine, 24% amphetamines, and 10% heroin. Ongoing drug use during study follow-up was reported by 9% using cocaine, 4% amphetamines, and 1% heroin. Hard drug (cocaine, amphetamines, or heroin) users had 2.1 times higher odds (p=0.001) of ART non-adherence in GEE models and 2.5 times higher risk (p=0.04) of AIDS progression or death in Cox models. Use of hard drugs was attenuated as a risk factor for AIDS progression or death after controlling for non-adherence during follow-up (HR=2.11, p=0.08), but was still suggestive of a possible adherence-independent mechanism of harm. This study highlights the need to continuously screen and treat patients for drug use as a part of ongoing HIV care

Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer.

PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR CONCLUSION: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile

Antisocial behaviour and teacher–student relationship quality: The role of emotion‐related abilities and callous–unemotional traits

Background: Childhood antisocial behaviour has been associated with poorer teacher-student relationship (TSR) quality. It is also well-established that youth with antisocial behaviour have a range of emotion-related deficits, yet the impact of these students’ emotion-related abilities on the TSR is not understood. Furthermore, the addition of the Limited Prosocial Emotions specifier in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) indicates that understanding the role of callous-unemotional (CU) traits for youth with antisocial behaviour problems is of particular importance. Aims: The aim of this study was to investigate the association between antisocial behaviour difficulties and the TSR by examining the influence of emotion-related abilities and CU traits. Sample: Twelve teachers from 10 primary schools provided anonymised information on 108 children aged 6-11 years. Results: Antisocial behaviour was associated with higher teacher-student conflict (but not closeness) as well as higher emotion lability/negativity and lower emotion understanding/empathy. Emotion lability/negativity was associated with higher teacher-student conflict (but not closeness), and emotion understanding/empathy was associated with lower teacher-student conflict and higher closeness. CU traits was associated with higher teacher-student conflict and lower teacher-student closeness (controlling for antisocial behaviour more broadly). We found no evidence of a moderating effect of CU traits or emotion-related abilities on the association between antisocial behaviour and TSR quality. Conclusions: Interventions for behaviour difficulties should consider teacher-student relationships in the classroom. Strategies which aim to improve teacher-student closeness as well as reduce teacher-student conflict may be of particular value to students with high CU traits

ABCC Multidrug Transporters in Childhood Neuroblastoma: Clinical and Biological Effects Independent of Cytotoxic Drug Efflux

Background Although the prognostic value of the ATP-binding cassette, subfamily C (ABCC) transporters in childhood neuroblastoma is usually attributed to their role in cytotoxic drug efflux, certain observations have suggested that these multidrug transporters might contribute to the malignant phenotype independent of cytotoxic drug efflux. Methods A v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN)-driven transgenic mouse neuroblastoma model was crossed with an Abcc1-deficient mouse strain (658 hMYCN1/−, 205 hMYCN+/1 mice) or, alternatively, treated with the ABCC1 inhibitor, Reversan (n = 20). ABCC genes were suppressed using short interfering RNA or overexpressed by stable transfection in neuroblastoma cell lines BE(2)-C, SH-EP, and SH-SY5Y, which were then assessed for wound closure ability, clonogenic capacity, morphological differentiation, and cell growth. Real-time quantitative polymerase chain reaction was used to examine the clinical significance of ABCC family gene expression in a large prospectively accrued cohort of patients (n = 209) with primary neuroblastomas. Kaplan-Meier survival analysis and Cox regression were used to test for associations with event-free and overall survival. Except where noted, all statistical tests were two-sided. Results Inhibition of ABCC1 statistically significantly inhibited neuroblastoma development in hMYCN transgenic mice (mean age for palpable tumor: treated mice, 47.2 days; control mice, 41.9 days; hazard ratio [HR] = 9.3, 95% confidence interval [CI] = 2.65 to 32; P < .001). Suppression of ABCC1 in vitro inhibited wound closure (P < .001) and clonogenicity (P = .006); suppression of ABCC4 enhanced morphological differentiation (P < .001) and inhibited cell growth (P < .001). Analysis of 209 neuroblastoma patient tumors revealed that, in contrast with ABCC1 and ABCC4, low rather than high ABCC3 expression was associated with reduced event-free survival (HR of recurrence or death = 2.4, 95% CI = 1.4 to 4.2; P = .001), with 23 of 53 patients with low ABCC3 expression experiencing recurrence or death compared with 31 of 155 patients with high ABCC3. Moreover, overexpression of ABCC3 in vitro inhibited neuroblastoma cell migration (P < .001) and clonogenicity (P = .03). The combined expression of ABCC1, ABCC3, and ABCC4 was associated with patients having an adverse event, such that of the 12 patients with the "poor prognosis” expression pattern, 10 experienced recurrence or death (HR of recurrence or death = 12.3, 95% CI = 6 to 27; P < .001). Conclusion ABCC transporters can affect neuroblastoma biology independently of their role in chemotherapeutic drug efflux, enhancing their potential as targets for therapeutic interventio

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515(+)); median survival was 88 days (range 1–515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.co