Induction of prostacyclin receptor expression in human erythroleukemia cells

AbstractWe have identified both high-affinity (KD = 36±3 nM) and low-affinity (KD = 2.1±0.8 μM) prostacyclin (PGI2)-receptor sites on human erythroleukemia (HEL) cells using the radiolabelled prostacyclin analogue, [3H]iloprost. The addition of the phorbol ester, TPA, to the culture medium caused a 5–10-fold increase in the number of both the low- and the high-affinity sites, without any change in their affinity constants. Iloprost stimulated HEL cell membrane adenylate cyclase activity 5-fold. This stimulation was potentiated in the presence of GTP, indicating a conventional PGI2 receptor-Gs-adenylate cyclase system. HEL cells represent a source of prostacyclin receptor mRNA which may be of value in expression cloning of this receptor

Understanding tensions and identifying clinician agreement on improvements to early-stage chronic kidney disease monitoring in primary care : a qualitative study

Funding This article presents independent research funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR) (reference:120). JE was also supported by the NIHR Programme Grants for Applied Research programme (Reference: RP-PG-1210-12012). DSL and LL are supported by the NIHR Oxford Biomedical Research CentrePeer reviewedPublisher PD

The determination of planetary structure in tidally relaxed inclined systems

[Abridged] The recent discovery of a transiting planet on a non-circular orbit with a massive highly eccentric companion orbiting HAT-P-13 offers the possibility of probing the structure of the short-period planet. The ability to do this relies on the system being in a quasi-equilibrium state in the sense that the eccentricities are constant on the usual secular timescale, and decay on a timescale which is much longer than the age of the system. Since the equilibrium eccentricity is effectively a function only of observable system parameters and the unknown Love number of the short-period planet, the latter can be determined with accurate measurements of the planet's eccentricity and radius. However, this analysis relies on the unlikely assumption that the system is coplanar. Here we generalize our recent analysis of this fixed-point phenomenon to mutually inclined systems and show that the fixed point of coplanar systems is replaced by a limit cycle, with the average value of the eccentricity decreasing and its amplitude of variation increasing with increasing mutual inclination. This behaviour significantly reduces the ability to unambiguously determine the Love number of the short-period planet if the mutual inclination is higher than around 10^o. We show that for Q-values less than 10^6, the HAT-P-13 system cannot have a mutual inclination between 54 and 126^o because Kozai oscillations coupled with tidal dissipation would act to quickly move the inclination outside this range, and that the behaviour of retrograde systems is the mirror image of that for prograde systems. We derive a relationship between the equilibrium radius of the short-period planet, its Q-value and its core mass, and show that given current estimates of e_b and the planet radius, the HAT-P-13 system is likely to be close to coplanar [...]Comment: 24 pages, 14 figures, Accepted for publication in MNRAS. **NOTE REFINED PREDICTION FOR MUTUAL INCLINATIO

Outcomes of conduct problems in adolescence: 40 year follow-up of national cohort

Objective To describe long term outcomes associated with externalising behaviour in adolescence, defined in this study as conduct problems reported by a teacher, in a population based sample

English stop-smoking services: one-year outcomes

The UK is a global leader in stop-smoking support—providing free behavioral support and cessation medication via stop smoking services (SSS) without charge to smokers. This study aimed to explore the client and service characteristics associated with abstinence 52 weeks after quitting. A prospective cohort study of 3057 SSS clients in nine different areas of England who began their quit attempt between March 2012 and March 2013 was conducted. Important determinants of long-term quitting were assessed through quit rates and multivariable logistic regression. Our results showed that the overall weighted carbon monoxide validated quit rate for clients at 52 weeks was 7.7% (95% confidence interval (CI) 6.6–9.0). The clients of advisors, whose main role was providing stop-smoking support, were more likely to quit long-term than advisors who had a generalist role in pharmacies or general practices (odds ratio (OR) 2.3 (95% CI 1.2–4.6)). Clients were more likely to achieve abstinence through group support than one-to-one support (OR 3.4 (95% CI 1.7–6.7)). Overall, one in thirteen people who set a quit date with the National Health Service (NHS) Stop-Smoking Service maintain abstinence for a year. Improving abstinence is likely to require a greater emphasis on providing specialist smoking cessation support. Results from this study suggest that over 18,000 premature deaths were prevented through longer-term smoking cessation achieved by smokers who accessed SSS in England from March 2012 to April 2013, but outcomes varied by client characteristic and the type of support provided

Data collection tools for: "Changing rainfall patterns, household water use and health: risks and household responses in rural Gambia"

The overall aim of the study was to identify the household behavioural responses to changes in rainfall patterns by rural communities in The Gambia, and the risks or benefits to health these responses may pose. This collection contains topic guides used for semi-structured interviews performed with men and women (first-round and follow-up), topic guides for follow-up interviews with village elders/chiefs, picture cards used in ranking exercises during follow -up interview with women and men, and coding used for analysis of qualitative interviews

Determining the date of diagnosis – is it a simple matter? The impact of different approaches to dating diagnosis on estimates of delayed care for ovarian cancer in UK primary care

Background Studies of cancer incidence and early management will increasingly draw on routine electronic patient records. However, data may be incomplete or inaccurate. We developed a generalisable strategy for investigating presenting symptoms and delays in diagnosis using ovarian cancer as an example. Methods The General Practice Research Database was used to investigate the time between first report of symptom and diagnosis of 344 women diagnosed with ovarian cancer between 01/06/2002 and 31/05/2008. Effects of possible inaccuracies in dating of diagnosis on the frequencies and timing of the most commonly reported symptoms were investigated using four increasingly inclusive definitions of first diagnosis/suspicion: 1. "Definite diagnosis" 2. "Ambiguous diagnosis" 3. "First treatment or complication suggesting pre-existing diagnosis", 4 "First relevant test or referral". Results The most commonly coded symptoms before a definite diagnosis of ovarian cancer, were abdominal pain (41%), urogenital problems(25%), abdominal distension (24%), constipation/change in bowel habits (23%) with 70% of cases reporting at least one of these. The median time between first reporting each of these symptoms and diagnosis was 13, 21, 9.5 and 8.5 weeks respectively. 19% had a code for definitions 2 or 3 prior to definite diagnosis and 73% a code for 4. However, the proportion with symptoms and the delays were similar for all four definitions except 4, where the median delay was 8, 8, 3, 10 and 0 weeks respectively. Conclusion Symptoms recorded in the General Practice Research Database are similar to those reported in the literature, although their frequency is lower than in studies based on self-report. Generalisable strategies for exploring the impact of recording practice on date of diagnosis in electronic patient records are recommended, and studies which date diagnoses in GP records need to present sensitivity analyses based on investigation, referral and diagnosis data. Free text information may be essential in obtaining accurate estimates of incidence, and for accurate dating of diagnoses