The collecting activities of Sir John Lubbock (1834-1913).

In 2 vols.Available from British Library Document Supply Centre-DSC:DXN042838 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Developing a service for patients with very severe chronic obstructive pulmonary disease (COPD) within resources

Chronic obstructive pulmonary disease (COPD) is a common life-limiting illness with significant burden for patient and carer. Despite this, access to supportive and specialist palliative care is inconsistent and implementation of published good practice recommendations may be challenging within current resources. The aim of this service development was to improve local service provision in Barnsley, within the currently available resources, for patients with very severe COPD, to improve patient identification and symptom management, increase advance care planning and the numbers of patients dying in their preferred place, and increase patient and carer support and satisfaction. To do this a working group was formed, the service problems identified and baseline data collected to identify the needs of people with very severe COPD. A multidisciplinary team meeting was piloted and assessed by community matron feedback, patient case studies and an after death analysis. These indicated a high level of satisfaction, with improvements in advance care planning, co-ordination of management and support for patients' preferred place of care at the end of life. In conclusion this is the first reported very severe COPD service development established in this way and within current resources. Preliminary data indicates the development of the multidisciplinary team meeting has been positive. The appointment of a coordinator will aid this development. Further evaluations particularly seeking patient views and estimations of cost savings will be performed

Family-based association study of the BDNF, COMT and serotonin transporter genes and DSM-IV bipolar-I disorder in children

Background: Over the past decade pediatric bipolar disorder has gained recognition as a potentially more severe and heritable form of the disorder. In this report we test for association with genes coding brain-derived neurotrophic factor (BDNF), the serotonin transporter (SLC6A4), and catechol-O-methyltransferase (COMT). Methods: Bipolar-I affected offspring triads (N = 173) were drawn from 522 individuals with 2 parents in 332 nuclear families recruited for genetic studies of pediatric psychopathology at the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital. Results: We failed to identify an association with the val66 allele in BDNF (OR = 1.23, p = 0.36), the COMT-l allele (OR = 1.27, p = 0.1), or the HTTLPR short allele (OR = 0.87, p = 0.38). Conclusion: Our study suggests that the markers examined thus far in COMT and SLC6A4 are not associated with pediatric bipolar disorder and that if the val66met marker in BDNF is associated with pediatric bipolar disorder the magnitude of the association is much smaller than first reported

Expression of KOC, S100P, mesothelin and MUC1 in pancreatico-biliary adenocarcinomas: development and utility of a potential diagnostic immunohistochemistry panel

<b>Background</b> Pancreatico-biliary adenocarcinomas (PBA) have a poor prognosis. Diagnosis is usually achieved by imaging and/or endoscopy with confirmatory cytology. Cytological interpretation can be difficult especially in the setting of chronic pancreatitis/cholangitis. Immunohistochemistry (IHC) biomarkers could act as an adjunct to cytology to improve the diagnosis. Thus, we performed a meta-analysis and selected KOC, S100P, mesothelin and MUC1 for further validation in PBA resection specimens.<p></p> <b>Methods</b> Tissue microarrays containing tumour and normal cores in a ratio of 3:2, from 99 surgically resected PBA patients, were used for IHC. IHC was performed on an automated platform using antibodies against KOC, S100P, mesothelin and MUC1. Tissue cores were scored for staining intensity and proportion of tissue stained using a Histoscore method (range, 0–300). Sensitivity and specificity for individual biomarkers, as well as biomarker panels, were determined with different cut-offs for positivity and compared by summary receiver operating characteristic (ROC) curve.<p></p> <b>Results</b> The expression of all four biomarkers was high in PBA versus normal ducts, with a mean Histoscore of 150 vs. 0.4 for KOC, 165 vs. 0.3 for S100P, 115 vs. 0.5 for mesothelin and 200 vs. 14 for MUC1 (p < .0001 for all comparisons). Five cut-offs were carefully chosen for sensitivity/specificity analysis. Four of these cut-offs, namely 5%, 10% or 20% positive cells and Histoscore 20 were identified using ROC curve analysis and the fifth cut-off was moderate-strong staining intensity. Using 20% positive cells as a cut-off achieved higher sensitivity/specificity values: KOC 84%/100%; S100P 83%/100%; mesothelin 88%/92%; and MUC1 89%/63%. Analysis of a panel of KOC, S100P and mesothelin achieved 100% sensitivity and 99% specificity if at least 2 biomarkers were positive for 10% cut-off; and 100% sensitivity and specificity for 20% cut-off.<p></p> <b>Conclusion</b> A biomarker panel of KOC, S100P and mesothelin with at least 2 biomarkers positive was found to be an optimum panel with both 10% and 20% cut-offs in resection specimens from patients with PBA.<p></p&gt

Inbreeding Depression and Ovule Pre-emption in 'Bulbine bulbosa' (R. Br.) Haw. (Asphodelaceae)

This thesis examines the causes of self-sterility and consequences of inbreeding on seed set and progeny fitness in 'Bulbine bulbosa' (Asphodelaceae). I conducted my research utilising both glasshouse plants and natural populations of 'B. bulbosa'. I investigated the causes of reduced self-fertility. Two mechanisms can be responsible for self-infertility in hermaphroditic flowers: physiological self-incompatibility and inbreeding depression. I conducted a histological investigation of ovule development after self- and cross-pollination, up to 7-days post-pollination. Examination of cleared specimens at 2-days post-pollination indicated that the mechanism reducing self-fertility was post-zygotic because double fertilisation was apparent after both self- and cross-pollination. This eliminated gametophytic and sporophytic self-incompatibility. Examinations of ovule development at 5- and 7-days post-pollination indicated that abortion was significantly higher after self-compared to cross-pollination. There was no indication that the arrest of selfed ovule development occurred at a single stage, eliminating a late-acting physiological self-incompatibility mechanism. The evidence indicated that reduced self-fertility was probably due to early-acting inbreeding depression. I conclude that inbreeding facilitated by both selfing and mating between related individuals is costly to 'B. bulbosa' populations. Inbreeding results in inbreeding depression causing ovules to abort reducing natural seed set. Consequently, these ovules are wasted and are unavailable for outcrossing. Inbreeding reduces fecundity and potentially recruitment to successive generations. Finally, inbreeding depression is a major selective force maintaining a predominately outcrossing mating system in 'B. bulbosa'

Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives

<p>Abstract</p> <p>Background</p> <p>The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined.</p> <p>Results</p> <p>To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and <it>Foxa2 </it>mutant embryos at late gastrulation stage (E7.5). We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount <it>in situ </it>hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm.</p> <p>Conclusion</p> <p>The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer and its inductive properties in an otherwise normal embryo, impacts on the molecular profile of surrounding tissues.</p

What is best practice in sex and relationship education? A synthesis of evidence, including stakeholders' views.

OBJECTIVES: Sex and relationship education (SRE) is regarded as vital to improving young people's sexual health, but a third of schools in England lacks good SRE and government guidance is outdated. We aimed to identify what makes SRE programmes effective, acceptable, sustainable and capable of faithful implementation. DESIGN: This is a synthesis of findings from five research packages that we conducted (practitioner interviews, case study investigation, National Survey of Sexual Attitudes and Lifestyles, review of reviews and qualitative synthesis). We also gained feedback on our research from stakeholder consultations. SETTINGS: Primary research and stakeholder consultations were conducted in the UK. Secondary research draws on studies worldwide. RESULTS: Our findings indicate that school-based SRE and school-linked sexual health services can be effective at improving sexual health. We found professional consensus that good programmes start in primary school. Professionals and young people agreed that good programmes are age-appropriate, interactive and take place in a safe environment. Some young women reported preferring single-sex classes, but young men appeared to want mixed classes. Young people and professionals agreed that SRE should take a 'life skills' approach and not focus on abstinence. Young people advocated a 'sex-positive' approach but reported this was lacking. Young people and professionals agreed that SRE should discuss risks, but young people indicated that approaches to risk need revising. Professionals felt teachers should be involved in SRE delivery, but many young people reported disliking having their teachers deliver SRE and we found that key messages could become lost when interpreted by teachers. The divergence between young people and professionals was echoed by stakeholders. We developed criteria for best practice based on the evidence. CONCLUSIONS: We identified key features of effective and acceptable SRE. Our best practice criteria can be used to evaluate existing programmes, contribute to the development of new programmes and inform consultations around statutory SRE