Extending The Jamaican Early Childhood Development Intervention

We review the development of the Jamaican home visiting intervention for children under 4 years and its evidence base. The intervention has focused on supporting mothers to promote the development of their children through interacting in a responsive way, labelling the environment and activities. The curriculum is structured and cognitively orientated. It has been used in 13 studies in 4 countries, 7 in Jamaica, 6 in Bangladesh, one each in Colombia and Peru. In all studies some benefit to children’s cognitive and language development has been found. Different types of children from severely malnourished to children living in poverty have benefited. Three long term follow ups have found sustained benefits to cognition; the longest study went to 22 years and found comprehensive benefits, to behaviour, school attainment and achievement, IQ, depression and wages. The curriculum is currently being used in 8 different countries and different delivery strategies are being evaluated including mother and child groups with meetings of different frequencies. A web package, Reach Up, to facilitate training with manuals and demonstration videos has been developed. Some unanswered questions include, what is the most effective age and duration for the intervention to have sustained benefits? Research is needed to find cost-effective implementation models and how to monitor and maintain intervention quality when going to scale

Studies on a thiol-dependent reductase and ascorbate metabolism of leishmania

The intracellular protozoan parasite Leishmania causes leishmaniasis, a disease which is most prevalent in tropical and sub-tropical countries where it infects some two million people every year and kills around 60,000 of them. For decades pentavalent antimonial compounds have been the standard first-line drugs used to treat the disease and this remains the case despite increasing reports of drug-resistance. The mode of action of these drugs is not entirely understood, although it is generally accepted that in vivo reduction of the compounds from the pentavalent to a trivalent form is required for antileishmanial activity. The site of antimonial conversion and whether the reaction is catalysed by an enzyme remain controversial points. However, it was recently reported that L. donovani amastigotes were capable of reducing pentavalent antimonials to the trivalent form and that drug-resistant parasites were deficient in this activity, suggesting that a parasite enzyme did mediate drug toxicity. The identity of such an enzyme was investigated in this study. Arsenical and antimonial compounds are similar and several classes of proteins that exhibit arsenate reductase activity have been previously identified in other organisms. Whether Leishmania possessed an enzyme akin to one of these was assessed by attempting to purify enzymes from parasite lysates and by searching the L. major genome database for similar sequences to the arsenate reductases. The latter approach was successful and a gene fragment was identified that shared similarity with omega glutathione S-transferases (oGSTs), a class of glutaredoxin-like GSTs which are capable of reducing pentavalent methylated arsenicals in vitro. The sequence of the complete L. major gene was elucidated by 5' RACE, and was found to encode a protein twice the expected size with similar 3' and 5' halves. The protein was named thiol-dependent reductase, or TDRl. Active recombinant protein was successfully produced and its biochemical activities were found to coincide with oGSTs: TDRl was capable of reducing pentavalent arsenical and antimonial compounds to trivalent species, and possessed thioltransferase and dehydroascorbate reductase activities usually associated with glutaredoxins. TDRl, which was shown to probably reside in the parasite cytosol but may also be secreted, was found to be more abundant in amastigote than promastigote forms, which correlates with the antileishmanial stage-specificity of pentavalent antimonials. L. major TDRl knockout mutants were generated, and the protein was also over-expressed in parasites. Both these genetic manipulations resulted in mutants with enhanced infectivity. TDRl knockout parasites were more susceptible than wild type parasites to paraquat, which induces the production of intracellular superoxide. As its glutaredoxin-like in vitro activities suggest, this implies TDRl has a role in protecting the parasites from oxidative stress, although re-expression of TDRl did not reinstate resistance. (Abstract shortened by ProQuest.)

Patient experience of gastrointestinal endoscopy: Informing the development of the Newcastle ENDOPREM

Background Measuring patient experience is important for evaluating the quality of patient care, identifying aspects requiring improvement and optimising patient outcomes. Patient Reported Experience Measures (PREMs) should, ideally, be patient derived, however no such PREMs for gastrointestinal (GI) endoscopy exist. This study explored the experiences of patients undergoing GI endoscopy and CT colonography (CTC) in order to: identify aspects of care important to them; determine whether the same themes are relevant across investigative modalities; develop the framework for a GI endoscopy PREM. Methods Patients aged ≥18 years who had undergone oesophagogastroduodenoscopy (OGD), colonoscopy or CTC for symptoms or surveillance (but not within the national bowel cancer screening programme) in one hospital were invited to participate in semi-structured interviews. Recruitment continued until data saturation. Inductive thematic analysis was undertaken. Results 35 patients were interviewed (15 OGD, 10 colonoscopy, 10 CTC). Most patients described their experience chronologically, and five ‘procedural stages’ were evident: before attending for the test; preparing for the test; at the hospital, before the test; during the test; after the test. Six themes were identified: anxiety; expectations; choice & control; communication & information; comfort; embarrassment & dignity. These were present for all three procedures but not all procedure stages. Some themes were inter-related (eg, expectations & anxiety; communication & anxiety). Conclusion We identified six key themes encapsulating patient experience of GI procedures and these themes were evident for all procedures and across multiple procedure stages. These findings will be used to inform the development of the Newcastle ENDOPREM™

Uncertainty and the influence of group norms in the attitude–behaviour relationship

This is the author's post-print version of an article whose final and definitive form has been published in the British Journal of Social Psychology. Reproduced with permission from the British Journal of Social Psychology © The British Psychological Society 2007. The definitve version is available at: http://www.bpsjournals.co.uk/journals/bjsp/Two studies were conducted to examine the impact of subjective uncertainty on conformity to group norms in the attitude–behaviour context. In both studies, subjective uncertainty was manipulated using a deliberative mindset manipulation (McGregor, Zanna, Holmes, & Spencer, 2001). In Study 1 (N=106), participants were exposed to either an attitude-congruent or an attitude-incongruent in-group norm. In Study 2 (N=83), participants were exposed to either a congruent, incongruent, or an ambiguous in-group norm. Ranges of attitude–behaviour outcomes, including attitude-intention consistency and change in attitude-certainty, were assessed. In both studies, levels of group-normative behaviour varied as a function of uncertainty condition. In Study 1, conformity to group norms, as evidenced by variations in the level of attitude-intention consistency, was observed only in the high uncertainty condition. In Study 2, exposure to an ambiguous norm had different effects for those in the low and the high uncertainty conditions. In the low uncertainty condition, greatest conformity was observed in the attitude-congruent norm condition compared with an attitude-congruent or ambiguous norm. In contrast, individuals in the high uncertainty condition displayed greatest conformity when exposed to either an attitude-congruent or an ambiguous in-group norm. The implications of these results for the role of subjective uncertainty in social influence processes are discussed

Effect of pulsed delivery and bouillon base on saltiness and bitterness perceptions of salt delivery profiles partially substituted with KCl

Reducing salt levels in processed food is an important target for a growing numbers of food manufacturers. The effects of pulsed delivery (Dynataste) and bouillon base on saltiness and bitterness perception of partially substituted solutions (KCl) were investigated. Pulsed delivery did not enhance salt perception and resulted in greater Overall Bitterness Scores for the same level of substitution with KCl. The presence of the bouillon base masked to a certain extent the loss of saltiness induced by the substitution and resulted in lower Overall Bitterness Scores of the substituted profiles

The Newcastle ENDOPREM™: a validated patient reported experience measure for gastrointestinal endoscopy

Objectives Measuring patient experience of gastrointestinal (GI) procedures is a key component of evaluation of quality of care. Current measures of patient experience within GI endoscopy are largely clinician derived and measured; however, these do not fully represent the experiences of patients themselves. It is important to measure the entirety of experience and not just experience directly during the procedure. We aimed to develop a patient-reported experience measure (PREM) for GI procedures. Design Phase 1: semi-structured interviews were conducted in patients who had recently undergone GI endoscopy or CT colonography (CTC) (included as a comparator). Thematic analysis identified the aspects of experience important to patients. Phase 2: a question bank was developed from phase 1 findings, and iteratively refined through rounds of cognitive interviews with patients who had undergone GI procedures, resulting in a pilot PREM. Phase 3: patients who had attended for GI endoscopy or CTC were invited to complete the PREM. Psychometric properties were investigated. Phase 4 involved item reduction and refinement. Results Phase 1: interviews with 35 patients identified six overarching themes: anxiety, expectations, information & communication, embarrassment & dignity, choice & control and comfort. Phase 2: cognitive interviews refined questionnaire items and response options. Phase 3: the PREM was distributed to 1650 patients with 799 completing (48%). Psychometric properties were found to be robust. Phase 4: final questionnaire refined including 54 questions assessing patient experience across five temporal procedural stages. Conclusion This manuscript gives an overview of the development and validation of the Newcastle ENDOPREM™, which assesses all aspects of the GI procedure experience from the patient perspective. It may be used to measure patient experience in clinical care and, in research, to compare patients’ experiences of different endoscopic interventions

Back to BAC: The Use of Infectious Clone Technologies for Viral Mutagenesis

Bacterial artificial chromosome (BAC) vectors were first developed to facilitate the propagation and manipulation of large DNA fragments in molecular biology studies for uses such as genome sequencing projects and genetic disease models. To facilitate these studies, methodologies have been developed to introduce specific mutations that can be directly applied to the mutagenesis of infectious clones (icBAC) using BAC technologies. This has resulted in rapid identification of gene function and expression at unprecedented rates. Here we review the major developments in BAC mutagenesis in vitro. This review summarises the technologies used to construct and introduce mutations into herpesvirus icBAC. It also explores developing technologies likely to provide the next leap in understanding these important viruses

Case-finding for common mental disorders of anxiety and depression in primary care: an external validation of routinely collected data

Background The robustness of epidemiological research using routinely collected primary care electronic data to support policy and practice for common mental disorders (CMD) anxiety and depression would be greatly enhanced by appropriate validation of diagnostic codes and algorithms for data extraction. We aimed to create a robust research platform for CMD using population-based, routinely collected primary care electronic data. Methods We developed a set of Read code lists (diagnosis, symptoms, treatments) for the identification of anxiety and depression in the General Practice Database (GPD) within the Secure Anonymised Information Linkage Databank at Swansea University, and assessed 12 algorithms for Read codes to define cases according to various criteria. Annual incidence rates were calculated per 1000 person years at risk (PYAR) to assess recording practice for these CMD between January 1st 2000 and December 31st 2009. We anonymously linked the 2799 MHI-5 Caerphilly Health and Social Needs Survey (CHSNS) respondents aged 18 to 74 years to their routinely collected GP data in SAIL. We estimated the sensitivity, specificity and positive predictive value of the various algorithms using the MHI-5 as the gold standard. Results The incidence of combined depression/anxiety diagnoses remained stable over the ten-year period in a population of over 500,000 but symptoms increased from 6.5 to 20.7 per 1000 PYAR. A ‘historical’ GP diagnosis for depression/anxiety currently treated plus a current diagnosis (treated or untreated) resulted in a specificity of 0.96, sensitivity 0.29 and PPV 0.76. Adding current symptom codes improved sensitivity (0.32) with a marginal effect on specificity (0.95) and PPV (0.74). Conclusions We have developed an algorithm with a high specificity and PPV of detecting cases of anxiety and depression from routine GP data that incorporates symptom codes to reflect GP coding behaviour. We have demonstrated that using diagnosis and current treatment alone to identify cases for depression and anxiety using routinely collected primary care data will miss a number of true cases given changes in GP recording behaviour. The Read code lists plus the developed algorithms will be applicable to other routinely collected primary care datasets, creating a platform for future e-cohort research into these conditions. Keyword

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure