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

Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects

Self-Assembling Proteins as High-Performance Substrates for Embryonic Stem Cell Self-Renewal

The development of extracellular matrix mimetics that imitate niche stem cell microenvironments and support cell growth for technological applications is intensely pursued. Specifically, mimetics are sought that can enact control over the self-renewal and directed differentiation of human pluripotent stem cells (hPSCs) for clinical use. Despite considerable progress in the field, a major impediment to the clinical translation of hPSCs is the difficulty and high cost of large-scale cell production under xeno-free culture conditions using current matrices. Here, a bioactive, recombinant, protein-based polymer, termed ZT Fn , is presented that closely mimics human plasma fibronectin and serves as an economical, xeno-free, biodegradable, and functionally adaptable cell substrate. The ZT Fn substrate supports with high performance the propagation and long-term self-renewal of human embryonic stem cells while preserving their pluripotency. The ZT Fn polymer can, therefore, be proposed as an efficient and affordable replacement for fibronectin in clinical grade cell culturing. Further, it can be postulated that the ZT polymer has significant engineering potential for further orthogonal functionalization in complex cell applications

Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36–73), treated by 5-FU-based chemotherapy in different French institutions and who developed unanticipated 5-FU-related toxicity. Lymphocyte samples (standard collection procedure) were sent to us for DPD determination (biochemical method). Among the whole group of 53 patients, 19 had a significant DPD deficiency (DD; below 150 fmol min−1 mg−1 protein, i.e. less than 70% of the mean value observed from previous population study). There was a greater majority of women in the DD group (15 out of 19, 79%) compared with the remaining 34 patients (15 out of 34, 44%, P<0.014). Toxicity was often severe, leading to patient death in two cases (both women). The toxicity score (sum of WHO grading, theoritical range 0–20) was twice as high in patients with marked DD (below 100 pmol min−1 mg−1 protein, n = 11, mean score = 13.2) compared with patients with moderate DD (between 150 and 100 pmol min−1 mg−1 protein, n = 8, mean score = 6.8), P = 0.008. In the DD group, there was a high frequency of neurotoxic syndromes (7 out of 19, 37%). The two deceased patients both had severe neurotoxicity. The occurrence of cardiac toxicity was relatively rare (1 out of 19, 5%). These data suggest that women are particularly prone to DPD deficiency and allow a more precise definition of the DD toxicity profile. © 1999 Cancer Research Campaig

Accommodating conscientious objection in the midwifery workforce: a ratio-data analysis of midwives, birth and late abortions in 18 European countries in 2016.

BACKGROUND: In recent years, the role of a midwife has expanded to include the provision of abortion-related care. The laws on abortion in many European countries allow for those who hold a conscientious objection to participating to refrain from such participation. However, some writers have expressed concerns that this may have a detrimental effect on the workforce and limit women's access to the service. METHOD: The aim of this study was to provide a picture of the potential exposure midwives in Europe have to late abortions, an important factor in the integration of accommodation of conscientious objection to abortion by midwives into workload planning. We collected data from Ministries of Health or government statistical departments in 32 European countries on numbers of births, abortions, late abortions and midwives in 2016. We conducted a ratio-data analysis in those countries that met the inclusion criteria. RESULTS: Eighteen of the 32 countries provided full data; thus, our calculations are based on a total of 4 036 633 live births, 49 834 late abortions and a total of 132 071 midwives. The calculated ratios of live births to midwife, abortions to midwife and late abortions to midwife illustrate the wide variations between countries in relation to ratios of midwives to live births (15.22-53.99) and late abortions (0.17-1.47) CONCLUSIONS: This study provides the first comprehensive insight to ratios relating to birth and abortion, especially late abortion services, with regard to the midwifery workforce. It is essential to improve the reporting of abortion data and access to it within Europe to support evidence-informed decisions on optimising the contribution of the midwifery workforce especially within highly contentious fields such as abortion services. The study's findings suggest that there should be neither be any difficulty for those who are responsible for workload allocation nor compromises to a women's right to abortion services

Rumen function and grazing behavior of early-lactation dairy cows supplemented with fodder beet

Fodder beet (FB) is a source of readily fermentable carbohydrate that can mitigate early spring herbage deficits and correct the negative energy balance experienced during early lactation in pastoral dairy systems of New Zealand. However, the low-fiber and high-soluble carbohydrate content of both FB bulb and spring herbage are factors that promote subacute ruminal acidosis, impairing rumen function and limiting the marginal milk production response to supplement. In a crossover experiment, 8 Holstein Friesian × Jersey early-lactation dairy cows were used to test the effect of supplementing 16 kg of dry matter (DM) of a grazed perennial ryegrass herbage with 6 kg of DM/d of FB bulb (FBH) versus herbage only (HO) on changes in rumen function and grazing behavior. Following 20 d of adaptation to diets, DM disappearance (%) of FB bulb (FBH cows only) and herbage were measured in sacco, separately. Cows were fasted overnight, and the ruminal contents were bailed the following morning (~0930 h) again to determine the pool size of volatile fatty acids, ammonia, and particle size of digesta, as well as to estimate the rate of ruminal outflow and degradation of neutral detergent fiber. The FBH diet did not alter DM intake, milk yield, or milk solid (fat + protein) production compared with HO. Supplementation of herbage with FB reduced ruminal pH compared with HO between ~0800 h and 1300 h each day. During each period, 1 cow experienced severe subacute ruminal acidosis (pH 180 min/d) during final adaptation to the target FB allocation. The FBH diet reduced the ruminal pool of acetate and ammonia, but increased the ruminal pool of butyrate and lactate compared with HO. When fed FB, rumination and grazing time increased and grazing intensity declined compared with cows fed HO. Despite increased rumination, the comminution of large particles declined 28% between the first and second rumen bailing when cows were fed FB, and in sacco DM disappearance of perennial ryegrass declined 18% compared with cows fed HO. These results indicate that grazing dairy cows supplemented with FB (40% of daily intake) increase rumination and mastication intensity to counteract reduced ruminal degradation of ryegrass herbage due to low ruminal fluid pH

The Study of Quantum Interference in Metallic Photonic Crystals Doped with Four-Level Quantum Dots

In this work, the absorption coefficient of a metallic photonic crystal doped with nanoparticles has been obtained using numerical simulation techniques. The effects of quantum interference and the concentration of doped particles on the absorption coefficient of the system have been investigated. The nanoparticles have been considered as semiconductor quantum dots which behave as a four-level quantum system and are driven by a single coherent laser field. The results show that changing the position of the photonic band gap about the resonant energy of the two lower levels directly affects the decay rate, and the system can be switched between transparent and opaque states if the probe laser field is tuned to the resonance frequency. These results provide an application for metallic nanostructures in the fabrication of new optical switches and photonic devices

Quality of Care for HIV Infection Provided by Ryan White Program-Supported versus Non-Ryan White Program-Supported Facilities

BACKGROUND: The Ryan White HIV/AIDS Care Act (now the Treatment Modernization Act; Ryan White Program, or RWP) is a source of federal public funding for HIV care in the United States. The Health Services and Resources Administration requires that facilities or providers who receive RWP funds ensure that HIV health services are accessible and delivered according to established HIV-related treatment guidelines. We used data from population-based samples of persons in care for HIV infection in three states to compare the quality of HIV care in facilities supported by the RWP, with facilities not supported by the RWP. METHODOLOGY/PRINCIPAL FINDINGS: Within each area (King County in Washington State; southern Louisiana; and Michigan), a probability sample of patients receiving care for HIV infection in 1998 was drawn. Based on medical records abstraction, information was collected on prescription of antiretroviral therapy according to treatment recommendations, prescription of prophylactic therapy, and provision of recommended vaccinations and screening tests. We calculated population-level estimates of the extent to which HIV care was provided according to then-current treatment guidelines in RWP-supported and non-RWP-supported facilities. For all treatment outcomes analyzed, the compliance with care guidelines was at least as good for patients who received care at RWP-supported (vs non-RWP supported) facilities. For some outcomes in some states, delivery of recommended care was significantly more common for patients receiving care in RWP-supported facilities: for example, in Louisiana, patients receiving care in RWP-supported facilities were more likely to receive indicated prophylaxis for Pneumocystis jirovecii pneumonia and Mycobacterium avium complex, and in all three states, women receiving care in RWP-supported facilities were more likely to have received an annual Pap smear. CONCLUSIONS/SIGNIFICANCE: The quality of HIV care provided in 1998 to patients in RWP-supported facilities was of equivalent or better quality than in non-RWP supported facilities; however, there were significant opportunities for improvement in all facility types. Data from population-based clinical outcomes surveillance data can be used as part of a broader strategy to evaluate the quality of publicly-supported HIV care