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We evaluate the utility of the National Surveys of Attitudes and Sexual Lifestyles (Natsal) undertaken in 2000 and 2010, before and after the introduction of the National Chlamydia Screening Programme, as an evidence source for estimating the change in prevalence of Chlamydia trachomatis (CT) in England, Scotland and Wales. Both the 2000 and 2010 surveys tested urine samples for CT by Nucleic Acid Amplification Tests (NAATs). We examined the sources of uncertainty in estimates of CT prevalence change, including sample size and adjustments for test sensitivity and specificity, survey non-response and informative non-response. In 2000, the unadjusted CT prevalence was 4.22% in women aged 18–24 years; in 2010, CT prevalence was 3.92%, a non-significant absolute difference of 0.30 percentage points (95% credible interval −2.8 to 2.0). In addition to uncertainty due to small sample size, estimates were sensitive to specificity, survey non-response or informative non-response, such that plausible changes in any one of these would be enough to either reverse or double any likely change in prevalence. Alternative ways of monitoring changes in CT incidence and prevalence over time are discussed.
The right ventricular adaptations early after surgery in infants with tetralogy of Fallot are important to understand the changes that occur later on in life; this physiology has not been fully delineated. We sought to assess early postoperative right ventricular remodelling in patients with tetralogy of Fallot by cardiac MRI.
Materials and method
Subjects with tetralogy of Fallot under 1 year of age were recruited following complete surgical repair for tetralogy of Fallot. Protocol-based cardiac MRI to assess anatomy, function, and flows was performed before hospital discharge using the feed and sleep technique, an unsedated imaging technique.
MRI was completed in 16 subjects at a median age of 77 days (interquartile range 114). There was normal ventricular ejection fraction and indexed right ventricular end-diastolic volume (48±13 cc/m2), but elevated right ventricular mass (z score 6.2±2.4). Subjects requiring a transannular patch or right ventricle to pulmonary artery conduit had moderate pulmonary insufficiency (regurgitant fraction 27±16%).
Early right ventricular remodelling after surgical repair for tetralogy of Fallot is characterised by significant pulmonary regurgitation, right ventricular hypertrophy, and lack of dilation. Performing cardiac MRI using the feed and sleep technique is feasible in infants younger than 5 months. These results might open new avenues to study longitudinal right ventricular changes in tetralogy of Fallot and to further explore the utility of unsedated MRI in patients with other types of CHDs.
Right ventricular function is a crucial determinant of long-term outcomes of children with heart disease. Quantification of right ventricular systolic and diastolic performance by echocardiography is of paramount importance, given the prevalence of children with heart disease, particularly those with involvement of the right heart, such as single or systemic right ventricles, tetralogy of Fallot, and pulmonary arterial hypertension. Identification of poor right ventricular performance can provide an opportunity to intervene. In this review, we will go through the different systolic and diastolic indices, as well as their application in practice. Quantification of right ventricular function is possible and should be routinely performed using a combination of different measures, taking into account each disease state. Quantification is extremely useful for individual patient follow-up. Laboratories should continue to strive to optimise reproducibility through quality improvement and quality assurance efforts in addition to investing in technology and training for new, promising techniques, such as three-dimensional echocardiography.
Patterns of sexual mixing are major determinants of sexually transmitted infection (STI) transmission, in particular the extent to which high-risk populations mix with low-risk populations. However, patterns of mixing in the general population are poorly understood. We analysed data from a national probability sample survey of households, the Health Survey for England 2010. A total of 943 heterosexual couples living together, where at least one partner was aged between 16–44 years, were included. We used correlation coefficients to measure the strength of similarities between partners with respect to demographic characteristics, general health, health behaviours and sexual history. Males were on average 2 years older than their female partners, although this age difference ranged from a median of 0 years in men aged 16–24 years to a median of 2 years in men aged 35–44 years. A positive correlation between partners was found for all demographic characteristics. With respect to general health and health behaviours, a strongly positive correlation was found between men and women in reporting alcohol consumption at ⩾3 days a week and smoking. Men typically reported greater numbers of sexual partners than their female partner, although men and women with more partners were more likely to mix with each other. We have been able to elucidate the patterns of sexual mixing between men and women living together in England. Mixing based on demographic characteristics was more assortative than sexual characteristics. These data can better inform mathematical models of STI transmission.
This review presents a progression strategy for the discovery of new anti-parasitic drugs that uses in vitro susceptibility, time-kill and reversibility measures to define the therapeutically relevant exposure required in target tissues of animal infection models. The strategy is exemplified by the discovery of SCYX-7158 as a potential oral treatment for stage 2 (CNS) Human African Trypanosomiasis (HAT). A critique of current treatments for stage 2 HAT is included to provide context for the challenges of achieving target tissue disposition and the need for establishing pharmacokinetic–pharmacodynamic (PK–PD) measures early in the discovery paradigm. The strategy comprises 3 stages. Initially, compounds demonstrating promising in vitro activity and selectivity for the target organism over mammalian cells are advanced to in vitro metabolic stability, barrier permeability and tissue binding assays to establish that they will likely achieve and maintain therapeutic concentrations during in-life efficacy studies. Secondly, in vitro time-kill and reversibility kinetics are employed to correlate exposure (based on unbound concentrations) with in vitro activity, and to identify pharmacodynamic measures that would best predict efficacy. Lastly, this information is used to design dosing regimens for pivotal pharmacokinetic–pharmacodyamic studies in animal infection models.
This study examined the relationship between levels of group cohesion, defined as whole group relationships, and between-session therapeutic homework adherence in a multi-family group therapy (MFGT) for people with schizophrenia. Participants from 18 consenting families attending MFGT groups completed weekly homework adherence ratings, group cohesion and spontaneous between-session activity measures. Levels of group cohesion at each session were compared with measures of scheduled and spontaneous homework adherence reported at the next session. It was hypothesised that higher levels of group cohesion would be related to homework adherence and other spontaneous between-session therapeutic activity completed by group members. Results show higher levels of group cohesion were associated with higher rates of spontaneous between-session therapeutic activity. However, contrary to expectations no significant relationship between cohesion and scheduled homework completion was found. The implications of the findings for group processes and homework adherence are discussed.
We report the discovery in the Greenland ice sheet of a discrete layer of free nanodiamonds (NDs) in very high abundances, implying most likely either an unprecedented influx of extraterrestrial (ET) material or a cosmic impact event that occurred after the last glacial episode. From that layer, we extracted n-diamonds and hexagonal diamonds (lonsdaleite), an accepted ET impact indicator, at abundances of up to about 5×106 times background levels in adjacent younger and older ice. The NDs in the concentrated layer are rounded, suggesting they most likely formed during a cosmic impact through some process similar to carbon-vapor deposition or high-explosive detonation. This morphology has not been reported previously in cosmic material, but has been observed in terrestrial impact material. This is the first highly enriched, discrete layer of NDs observed in glacial ice anywhere, and its presence indicates that ice caps are important archives of ET events of varying magnitudes. Using a preliminary ice chronology based on oxygen isotopes and dust stratigraphy, the ND-rich layer appears to be coeval with ND abundance peaks reported at numerous North American sites in a sedimentary layer, the Younger Dryas boundary layer (YDB), dating to 12.9 ± 0.1 ka. However, more investigation is needed to confirm this association.
The TEDI (TripleSpec - Exoplanet Discovery Instrument) is a dedicated instrument for the near-infrared radial velocity search for planetary companions to low-mass stars with the goal of achieving meters-per-second radial velocity precision. Heretofore, such planet searches have been limited almost entirely to the optical band and to stars that are bright in this band. Consequently, knowledge about planetary companions to the populous but visibly faint low-mass stars is limited. In addition to the opportunity afforded by precision radial velocity searches directly for planets around low mass stars, transits around the smallest M dwarfs offer a chance to detect the smallest possible planets in the habitable zones of the parent stars. As has been the the case with followup of planet candidates detected by the transit method requiring radial velocity confirmation, the capability to undertake efficient precision radial velocity measurements of mid-late M dwarfs will be required. TEDI has been commissioned on the Palomar 200” telescope in December 2007, and is currently in a science verification phase.
Respiratory syncytial virus (RSV) is an important cause of morbidity in children worldwide, although data from equatorial regions are limited. We analysed climatic, spatial, and temporal data for children presenting to hospitals in Lombok island, Indonesia with clinical pneumonia. During the study period, 2878 children presented and 741 RSV cases were identified. In multivariate analysis with an 8-day lag, occurrence of rain was associated with 64% higher incidence of RSV disease [incidence rate ratio (IRR) 1·64, 95% confidence interval (CI) 1·13–2·38]. A 1% rise in mean relative humidity and 1°C increase in mean air temperature was associated with a 6% (IRR 1·06, 95% CI 1·03–1·10) and 44% (IRR 1·44, 95% CI 1·24–1·66) increase in RSV cases, respectively. Four statistically significant local clusters of RSV pneumonia were identified within the annual island-wide epidemics. This study demonstrates statistical association of monsoon-associated weather in equatorial Indonesia with RSV. Moreover, within the island-wide epidemics, localized RSV outbreaks suggest local factors influence RSV disease.
A holistic approach to care has traditionally been the central tenet of general practice in the UK. However, recent major changes in general practice may be diminishing the importance and/or deliverability of such an approach. We sought to explore the views of Scotland’s general practitioner (GP) principals. We surveyed all 3713 GP principals in Scotland during February to July 2001 by postal questionnaire. Nearly 9 in 10 GPs (87%) felt that a holistic approach was essential to providing good health care, but only 1 in 5 (21%) felt that primary care was currently delivering high-quality holistic care, and only 1 in 15 (7%) felt that the current organization of primary care was conducive to such care. Constraints on holism were thought to contribute significantly to higher rates of prescribing (73% agreed), more referrals to secondary care (63% agreed), and increased demand for complementary therapies (57% agreed). Psychological factors were considered to play an important role in organic physical disease – its causation (67% agreed), course (94% agreed) and reversal (69% agreed) – yet when either the GP or the patient wished to explore issues relating to stress or emotional difficulties the GPs felt significantly constrained, mainly by time and their own stress (mean values (95% CI); 0: not limiting, 10: extremely limiting; time 7.6 (7.49–7.67); stress 4.9 (4.84–5.04); training 4.7 (4.66–4.84); skills 4.2 (4.13–4.30); motivation 3.4 (3.33–3.50)). In this survey Scotland’s principal GPs overwhelmingly endorse the traditional holistic approach of general practice and primary care, but feel that it is failing to be delivered due to organizational and time constraints, with consequent human and financial costs. These results give voice to deep concerns among GPs who remain committed to a holism they are struggling to deliver.
We give on overview of recent advances in collisionally pumped optical
field-ionization soft X-ray lasers developed at LOA. Saturated
amplification has been achieved on the 5d-5p transition in Xe8+
at 41.8 nm, and on the 4d-4p transition in Kr8+ at 32.8 nm. We
demonstrate a significant increase of the energy output from the
Xe8+ laser driven within two types of wave-guide. Finally, we
present results of a pioneering work aimed to set up and characterize the
first true soft X-ray laser chain.
Connective tissues such as cartilage, tendon, skin, bone, and arteries are composite bio-materials that contain predominantly water, collagen, proteoglycans and hyaluronic acid. Like any composite material, the components themselves and their interactions dictate the properties of the material. Fibrillar collagens are the principal structural molecules of the connective tissues and require regulated assembly and growth. Previous work from our lab indicates that the amino propeptide (Npp) domain of collagen type XI α1 chain regulates fibril diameter growth. Npp is a globular domain that is thought to sterically hinder the dense packing assembly of collagen molecules in fibrils. This mechanism of regulating collagen fibril assembly may be more complex than steric hindrance. We hypothesize that the Npp domain has a more dynamic role in establishing the structure/function relationship of collagen fibrils in connective tissues. In this study, the molecular structure of Npp was predicted by modeling. The model predicted putative binding sites for heparan sulfate and divalent cations. These predicted binding sites were evaluated empirically by fluorescence spectroscopy and surface plasmon resonance.