The Organic Research Centre; Elm Farm Bulletin 84 July 2006

Regular bulletin with technical updates of the Organic Advisory Service Issue contains: Battling on for Avian Flu preventive vaccination; Organic Colombian Blacktail eggs; UK Co-existence - GMOand non-GMO crops; Aspects of Poultry Behaviour; CAP in the service of biodiversity; Seeing the Wood, the Trees and the Catch 22; Beware of organic market "statistics"; A central role in energy review

Elm Farm Organic Research Centre Bulletin 83 April 2006

Regular bulleting with technical updates from Organic Advisory Service Issue contains: Testing for Tolerance - a pragmatic view GM Debate Vaccination nation - to jab or not to jab Future shape of OCIS Evolutionary wheat makes the grade? NIAB tracks health of organic cereal seed Stopping erosion of soil quality - the organic way Care needed to halt butterfly collapse Aspects of poultry behaviour: How free range is free range? On choosing an organic wheat A local education challenge New Wakelyns Science Building Organic vegetable market growt

Constraining the provenance of the Stonehenge 'Altar Stone': Evidence from automated mineralogy and U–Pb zircon age dating

The Altar Stone at Stonehenge is a greenish sandstone thought to be of Late Silurian-Devonian (‘Old Red Sandstone’) age. It is classed as one of the bluestone lithologies which are considered to be exotic to the Salisbury Plain environ, most of which are derived from the Mynydd Preseli, in west Wales. However, no Old Red Sandstone rocks crop out in the Preseli; instead a source in the Lower Old Red Sandstone Cosheston Subgroup at Mill Bay to the south of the Preseli, has been proposed. More recently, on the basis of detailed petrography, a source for the Altar Stone much further to the east, towards the Wales-England border, has been suggested. Quantitative analyses presented here compare mineralogical data from proposed Stonehenge Altar Stone debris with samples from Milford Haven at Mill Bay, as well as with a second sandstone type found at Stonehenge which is Lower Palaeozoic in age. The Altar Stone samples have contrasting modal mineralogies to the other two sandstone types, especially in relation to the percentages of its calcite, kaolinite and barite cements. Further differences between the Altar Stone sandstone and the Cosheston Subgroup sandstone are seen when their contained zircons are compared, showing differing morphologies and U-Pb age dates having contrasting populations. These data confirm that Mill Bay is not the source of the Altar Stone with the abundance of kaolinite in the Altar Stone sample suggesting a source further east, towards the Wales-England border. The disassociation of the Altar Stone and Milford Haven undermines the hypothesis that the bluestones, including the Altar Stone, were transported from west Wales by sea up the Bristol Channel and adds further credence to a totally land-based route, possibly along a natural routeway leading from west Wales to the Severn estuary and beyond. This route may well have been significant in prehistory, raising the possibility that the Altar Stone was added en route to the assemblage of Preseli bluestones taken to Stonehenge around or shortly before 3000 BC. Recent strontium isotope analysis of human and animal bones from Stonehenge, dating to the beginning of its first construction stage around 3000 BC, are consistent with the suggestion of connectivity between this western region of Britain and Salisbury Plain.This study appears to be the first application of quantitative automated mineralogy in the provenancing of archaeological lithic material and highlights the potential value of automated mineralogy in archaeological provenancing investigations, especially when combined with complementary techniques, in the present case zircon age dating

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. First, we assessed the effect of gestational VPA on fetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses which are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied - inbred Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic generalized epilepsy, and inbred Non-Epileptic Control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Fetuses were extracted via C-section on gestational day 21 (one day prior to birth) and fetal brains were snap frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes down-regulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function, and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic fetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation

The Use of Transdermal Estrogen in Castrate-resistant, Steroid-refractory Prostate Cancer

BACKGROUND: Androgen-deprivation therapy is the mainstay of treatment for metastatic prostate cancer. Corticosteroids and estrogens are also useful agents in castration-resistant prostate cancer (CRPC). However, oral estrogens are associated with thromboembolic events, which limits their use, and transdermal estrogens may offer a safer alternative. This study was carried out to determine the safety and effectiveness of transdermal estrogens in CRPC. PATIENTS AND METHODS: Forty-one patients with CRPC and steroid-resistant prostate cancer were eligible for this dose-escalation study of transdermal estradiol. A starting dose of 50 mcg/24 hours was applied and increased if prostate-specific antigen (PSA) rose > 5 ng/mL in steps to 300 mcg/24 hours. The primary endpoint was PSA response, and secondary outcomes included incidence of thromboembolic events and progression-free survival. Patients who progressed were offered diethylstilbestrol. RESULTS: Five (13%) of 40 patients had > 50% PSA reduction for at least 1 month at any transdermal estradiol dose. No venous-thromboembolic events were observed, and responses plateaued at 200 mcg/24 hours. A correlation between PSA response and rising sex hormone binding globulin was seen. Fifty percent of patients subsequently responded to low-dose diethylstilbestrol. CONCLUSION: Transdermal estradiol appears to be a low toxicity treatment option to control CRPC after failure of steroid therapy. Modulation of sex hormone binding globulin by transdermal estradiol may be one mechanism of action of estrogens on CRPC. Oral estrogens remain effective after the use of transdermal estradiol

Test of a Novel Streptococcus pneumoniae Serotype 6C Type Specific Polyclonal Antiserum (Factor Antiserum 6d) and Characterisation of Serotype 6C Isolates in Denmark

<p>Abstract</p> <p>Background</p> <p>In 2007, Park <it>et al. </it>identified a novel serotype among <it>Streptococcus pneumoniae </it>serogroup 6 which they named serotype 6C. The aim of this study was to evaluate with the Neufeld test a novel <it>S. pneumoniae </it>serotype 6C type specific polyclonal antiserum. In addition, serotype 6C isolates found in Denmark in 2007 and 2008 as well as eight old original serotype 6A isolates were characterised.</p> <p>Methods</p> <p>In this study, 181 clinical <it>Streptococcus pneumoniae </it>isolates from Denmark 2007 and 2008 were examined; 96 isolates had previously been typed as serotype 6A and 85 as serotype 6B. In addition, eight older isolates from 1952 to 1987, earlier serotyped as 6A, were examined. Serotype 6C isolates were identified by PCR and serotyping with the Neufeld test using the novel type specific polyclonal antiserum, factor antiserum 6 d, in addition to factor antisera 6b, 6b* (absorbed free for cross-reactions to serotype 6C) and 6c. All antisera are commercially available and antiserum 6b obtained from the supplier after 1 January 2009 is antiserum 6b*. All serotype 6C isolates were further characterised using multi-locus sequence typing.</p> <p>Results</p> <p>When retesting all 96 original serotype 6A isolates by PCR and the Neufeld test, 29.6% (24 of 81) of the invasive isolates in Denmark from 2007 and 2008 were recognised as serotype 6C. In addition, three of eight old isolates originally serotyped as 6A were identified to be serotype 6C. The oldest serotype 6C isolate was from 1962. The serotype 6C isolates belonged to eleven different sequence types (ST) and nine clonal complexes (CC), ST1692 (CC395), ST386 (CC386) and ST481 (CC460) were the predominant types.</p> <p>Conclusions</p> <p>We tested a novel polyclonal antiserum 6 d, as well as modified antiserum 6b*, provided a scheme for the serotyping of <it>S. pneumoniae </it>serogroup 6 using the Neufeld test and compared the serotyping method with PCR based methods. The two types of methods provided the same results. In future, it will, therefore, be possible to test also serotype 6C in accordance to the standard method for serotyping of <it>S. pneumoniae </it>recommended by WHO.</p> <p>Among all invasive isolates from Denmark 2007 and 2008, serotype 6C constituted 29.6% of the original serotype 6A isolates. The serotype 6C isolates were found to be diverse belonging to a number of different STs and CCs of which most have been observed in other countries previously. Serotype 6C is regarded as an "old" serotype being present among <it>S. pneumoniae </it>isolates in Denmark for at least 48 years. The genetic diversity of serotype 6C isolates and their genetic relationship to other serotypes suggested that serotype 6C strains may have arisen from several different independent recombination events involving different parental strains such as serotypes 6A, 6B, 23F and 4.</p

Designing theoretically-informed implementation interventions

Clinical and health services research is continually producing new findings that may contribute to effective and efficient patient care. However, the transfer of research findings into practice is unpredictable and can be a slow and haphazard process. Ideally, the choice of implementation strategies would be based upon evidence from randomised controlled trials or systematic reviews of a given implementation strategy. Unfortunately, reviews of implementation strategies consistently report effectiveness some, but not all of the time; possible causes of this variation are seldom reported or measured by the investigators in the original studies. Thus, any attempts to extrapolate from study settings to the real world are hampered by a lack of understanding of the effects of key elements of individuals, interventions, and the settings in which they were trialled. The explicit use of theory offers a way of addressing these issues and has a number of advantages, such as providing: a generalisable framework within which to represent the dimensions that implementation studies address, a process by which to inform the development and delivery of interventions, a guide when evaluating, and a way to allow for an exploration of potential causal mechanisms. However, the use of theory in designing implementation interventions is methodologically challenging for a number of reasons, including choosing between theories and faithfully translating theoretical constructs into interventions. The explicit use of theory offers potential advantages in terms of facilitating a better understanding of the generalisability and replicability of implementation interventions. However, this is a relatively unexplored methodological area

A qualitative study of health care professionals' views and experiences of paediatric advance care planning

Background: Good end-of-life care planning is vital to ensure optimal care is provided for patients and their families. Two key factors are open and honest advance care planning conversations between the patient (where possible), family, and health care professionals, focusing on exploring what their future wishes are; and the development of an advance care plan document. However, in paediatric and neonatal settings, there has been little research to demonstrate how advance care planning conversations take place. This study explored health care professionals' views and experiences of paediatric advance care planning in hospitals, community settings and hospices. Methods: A qualitative methodology was employed using purposive sampling of health care professionals involved in the end-of-life care for children aged 0-18 years known to the hospital palliative care team, and had died at least three months before, but less than 18 months prior to the study. Ethics committee approval was obtained for the study. Located in the North of England, the study involved three hospitals, a children's hospice, and community services. Data were collected using semi-structured, digitally recorded, telephone interviews. All interviews were transcribed verbatim and subjected to thematic analysis. Results: Twenty-one health care professionals participated, including generalist paediatric staff as well as specialist palliative care staff. Two themes were generated from the study: The timing of planning conversations, including waiting for the relationship with the family to form; the introduction of parallel planning; avoiding a crisis situation. Secondly, supporting effective conversations around advance care planning, including where to have the conversation; introducing the conversation; and how to approach the topic encompassing the value of advance care planning and documentation for families. Conclusion: The timing of when to start the advance care planning conversations remains an issue for health care professionals. The value of doing it in stages and considering the environment where the conversations are held was noted. Timely planning was seen as vital to avoid difficult conversations at a crisis point and for co-ordination of care. Good advance care planning is to provide the best person-centred care for the child and experience for the family

Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species