A Study of the Production of Neutrons for Boron Neutron Capture Therapy using a Proton Accelerator

Boron Neutron Capture Therapy (BNCT) is a binary cancer therapy particularly well-suited to treating aggressive tumours that exhibit a high degree of infiltration of the surrounding healthy tissue. Such tumours, for example of the brain and lung, provide some of the most challenging problems in oncology. The first element of the therapy is boron-10 which is preferentially introduced into the cancerous cells using a carrier compound. Boron-10 has a very high capture cross-section with the other element of the therapy, thermal neutrons, resulting in the production of a lithium nucleus and an alpha particle which destroy the cell they are created in. However, a large flux of neutrons is required and until recently the only source used was a nuclear reactor. In Birmingham, studies of an existing BNCT facility using a 2.8 MeV proton beam and a solid lithium target have found a way to increase the beam power to a sufficient level to allow clinical trials, while maintaining the target solid. In this paper, we will introduce BNCT, describe the work in Birmingham and compare with other accelerator-driven BNCT projects around the World

The returns to microenterprise support among the ultrapoor: A field experiment in postwar Uganda

This is the final version of the article. Available from American Economic Association via the DOI in this record.We show that extremely poor, war-affected women in northern Uganda have high returns to a package of $150 cash, five days of business skills training, and ongoing supervision. Sixteen months after grants, participants doubled their microenterprise ownership and incomes, mainly from petty trading. We also show these ultrapoor have too little social capital, but that group bonds, informal insurance, and cooperative activities could be induced and had positive returns. When the control group received cash and training 20 months later, we varied supervision, which represented half of the program costs. A year later, supervision increased business survival but not consumption. (JEL I38, J16, J23, J24, L26, O15, Z13

Association between somatic cell count early in the first lactation and the lifetime milk yield of cows in Irish dairy herds

Change in lifetime milk yield is an important component of the cost of diseases in dairy cows. Knowledge of the likelihood and scale of potential savings through disease prevention measures is important to evaluate how much expenditure on control measures is rational. The aim of this study was to assess the association between somatic cell count (SCC) at 5 to 30 d in milk during parity 1 (SCC1), and lifetime milk yield for cows in Irish dairy herds. The data set studied included records from 53,652 cows in 5,922 Irish herds. This was split into 2 samples of 2,500 and 3,422 herds at random. Linear models with lifetime milk yield and first-lactation milk yield as the outcomes and random effects to account for variation between herds were fitted to the data for the first sample of herds; data for the second sample were used for cross-validation. The models were developed in a Bayesian framework to include all uncertainty in posterior predictions and parameters were estimated from 10,000 Markov chain Monte Carlo simulations. The final model was a good fit to the data and appeared generalizable to other Irish herds. A unit increase in the natural logarithm of SCC1 was associated with a median decrease in lifetime milk yield of 864kg, and a median decrease in first-lactation milk yield of 105kg. To clarify the meaning of the results in context, microsimulation was used to model the trajectory of individual cows, and evaluate the expected outcomes for particular changes in the herd-level prevalence of cows with SCC1 ≥400,000cells/mL. Differences in mean lifetime milk yield associated with these changes were multiplied by an estimated gross margin for each cow to give the potential difference in milk revenue. Results were presented as probabilities of savings; for example, a 75% probability of savings of at least€97 or€115/heifer calved into the herd existed if the prevalence of cows with SCC1 ≥400,000cells/mL was reduced from ≥20 to <10 or <5%, respectively, and at least€71/heifer calved into the herd if the prevalence of cows with SCC1 ≥400,000cells/mL was reduced from ≥10 to <5%. The results indicate large differences in lifetime milk yield, depending on SCC early in the first lactation and the findings can be used to assess where specific interventions to control heifer mastitis prepartum are likely to be cost effective. Key words: dairy heifer, somatic cell count, lifetime milk yiel

Bayesian evaluation of budgets for endemic disease control: an example using management changes to reduce milksomatic cell count early in the first lactation of Irish dairy cows

The aim of this research was to determine budgets for specific management interventions to control heifer mastitis in Irish dairy herds as an example of evidence synthesis and 1-step Bayesian micro-simulation in a veterinary context. Budgets were determined for different decision makers based on their willingness to pay. Reducing the prevalence of heifers with a high milk somatic cell count (SCC) early in the first lactation could be achieved through herd level management interventions for pre- and peri-partum heifers, however the cost effectiveness of these interventions is unknown. A synthesis of multiple sources of evidence, accounting for variability and uncertainty in the available data is invaluable to inform decision makers around likely economic outcomes of investing in disease control measures. One analytical approach to this is Bayesian micro-simulation, where the trajectory of different individuals undergoing specific interventions is simulated. The classic micro-simulation framework was extended to encompass synthesis of evidence from 2 separate statistical models and previous research, with the outcome for an individual cow or herd assessed in terms of changes in lifetime milk yield, disposal risk, and likely financial returns conditional on the interventions being simultaneously applied. The 3 interventions tested were storage of bedding inside, decreasing transition yard stocking density, and spreading of bedding evenly in the calving area. Budgets for the interventions were determined based on the minimum expected return on investment, and the probability of the desired outcome. Budgets for interventions to control heifer mastitis were highly dependent on the decision maker's willingness to pay, and hence minimum expected return on investment. Understanding the requirements of decision makers and their rational spending limits would be useful for the development of specific interventions for particular farms to control heifer mastitis, and other endemic diseases. Keywords Bayesian; Micro-simulation; Dairy heifer; Mastitis control; Cost-effectiveness; Decision makin

Association of season and herd size with somatic cell count for cows in Irish,English, and Welsh dairy herds

The aims of this study were to describe associations of time of year, and herd size with cow somatic cell count (SCC) for Irish, English, and Welsh dairy herds. Random samples of 497 and 493 Irish herds, and two samples of 200 English and Welsh (UK) herds were selected. Random effects models for the natural logarithm of individual cow test day SCC were developed using data from herds in one sub-dataset from each country. Data from the second sub-datasets were used for cross validation. Baseline model results showed that geometric mean cow SCC (GSCC) in Irish herds was highest from February to August, and ranged from 111,000 cells/mL in May to 61,000 cells/mL in October. For cows in UK herds, GSCC ranged from 84,000 cells/mL in February and June, to 66,000 cells/mL in October. The results highlight the importance of monitoring cow SCC during spring and summer despite low bulk milk SCC at this time for Irish herds. GSCC was lowest in Irish herds of up to 130 cows (63,000 cells/mL), and increased for larger herds, reaching 68,000 cells/mL in herds of up to 300 cows. GSCC in UK herds was lowest for herds of 130–180 cows (60,000 cells/mL) and increased to 63,000 cells/mL in herds of 30 cows, and 68,000 cells/mL in herds of 300 cows. Importantly, these results suggest expansion may be associated with increased cow SCC, highlighting the importance of appropriate management, to benefit from potential economies of scale, in terms of udder health

Characterising hyperinsulinaemia induced insulin resistance in human skeletal muscle cells

Hyperinsulinaemia potentially contributes to insulin resistance in metabolic tissues, such as skeletal muscle. The purpose of these experiments was to characterise glucose uptake, insulin signalling and relevant gene expression in primary human skeletal muscle-derived cells (HMDCs), in response to prolonged insulin exposure (PIE) as a model of hyperinsulinaemia-induced insulin resistance. Differentiated HMDCs from healthy human donors were cultured with or without insulin (100 nM) for 3 days followed by an acute insulin stimulation. HMDCs exposed to PIE were characterised by impaired insulin-stimulated glucose uptake, blunted IRS-1 phosphorylation (Tyr612) and Akt (Ser473) phosphorylation in response to an acute insulin stimulation. Glucose transporter 1 (GLUT1), but not GLUT4, mRNA and protein increased following PIE. The mRNA expression of metabolic (PDK4) and inflammatory markers (TNF-α) was reduced by PIE but did not change lipid (SREBP1 and CD36) or mitochondrial (UCP3) markers. These experiments provide further characterisation of the effects of PIE as a model of hyperinsulinaemia-induced insulin resistance in HMDCs

Environmental exposures during windows of susceptibility for breast cancer: a framework for prevention research.

BackgroundThe long time from exposure to potentially harmful chemicals until breast cancer occurrence poses challenges for designing etiologic studies and for implementing successful prevention programs. Growing evidence from animal and human studies indicates that distinct time periods of heightened susceptibility to endocrine disruptors exist throughout the life course. The influence of environmental chemicals on breast cancer risk may be greater during several windows of susceptibility (WOS) in a woman's life, including prenatal development, puberty, pregnancy, and the menopausal transition. These time windows are considered as specific periods of susceptibility for breast cancer because significant structural and functional changes occur in the mammary gland, as well as alterations in the mammary micro-environment and hormone signaling that may influence risk. Breast cancer research focused on these breast cancer WOS will accelerate understanding of disease etiology and prevention.Main textDespite the plausible heightened mechanistic influences of environmental chemicals on breast cancer risk during time periods of change in the mammary gland's structure and function, most human studies of environmental chemicals are not focused on specific WOS. This article reviews studies conducted over the past few decades that have specifically addressed the effect of environmental chemicals and metals on breast cancer risk during at least one of these WOS. In addition to summarizing the broader evidence-base specific to WOS, we include discussion of the NIH-funded Breast Cancer and the Environment Research Program (BCERP) which included population-based and basic science research focused on specific WOS to evaluate associations between breast cancer risk and particular classes of endocrine-disrupting chemicals-including polycyclic aromatic hydrocarbons, perfluorinated compounds, polybrominated diphenyl ethers, and phenols-and metals. We outline ways in which ongoing transdisciplinary BCERP projects incorporate animal research and human epidemiologic studies in close partnership with community organizations and communication scientists to identify research priorities and effectively translate evidence-based findings to the public and policy makers.ConclusionsAn integrative model of breast cancer research is needed to determine the impact and mechanisms of action of endocrine disruptors at different WOS. By focusing on environmental chemical exposure during specific WOS, scientists and their community partners may identify when prevention efforts are likely to be most effective

Association between somatic cell count during the first lactation and the cumulative milk yield of cows in Irish dairy herds

Reduced potential milk yield is an important component of mastitis costs in dairy cows. The first aim of this study was to assess associations between somatic cell count (SCC) during the first lactation, and cumulative milk yield over the first lactation and subsequent lifetime of cows in Irish dairy herds. The second aim was to assess the association between SCC at 5 to 30 d in milk during parity 1 (SCC1), and SCC over the entire first lactation for cows in Irish dairy herds. The data set studied included records from 51,483 cows in 5,900 herds. Somatic cell count throughout the first lactation was summarized using the geometric mean and variance of SCC. Data were analyzed using linear models that included random effects to account for the lack of independence between observations, and herdlevel variation in coefficients. Models were developed in a Bayesian framework and parameters were estimated from 10,000 Markov chain Monte Carlo simulations. The final models were a good fit to the data. A 1-unit increase in mean natural logarithm SCC over the first lactation was associated with a median decrease in first lactation and lifetime milk yield of 135 and 1,663 kg, respectively. A 1-unit increase in the variance of natural logarithm SCC over the first lactation was associated with a median decrease in lifetime milk yield of 719 kg. To demonstrate the context of lifetime milk yield results, microsimulation was used to model the trajectory of individual cows and evaluate the expected outcomes for particular changes in herd-level geometric mean SCC over the first lactation. A 75% certainty of savings of at least €199/heifer in the herd was detected if herd-level geometric mean SCC over the first lactation was reduced from ≥120,000 to ≤72,000 cells/mL. The association between SCC1 and SCC over the remainder of the first lactation was highly herd dependent, indicating that control measures for heifer mastitis should be preferentially targeted on an individual-herd basis toward either the pre- and peripartum period, or the lactating period, to optimize the lifetime milk yield of dairy cows

Effects of ocean acidification on invertebrate settlement at volcanic CO<inf>2</inf> vents

We present the first study of the effects of ocean acidification on settlement of benthic invertebrates and microfauna. Artificial collectors were placed for 1 month along pH gradients at CO2 vents off Ischia (Tyrrhenian Sea, Italy). Seventy-nine taxa were identified from six main taxonomic groups (foraminiferans, nematodes, polychaetes, molluscs, crustaceans and chaetognaths). Calcareous foraminiferans, serpulid polychaetes, gastropods and bivalves showed highly significant reductions in recruitment to the collectors as pCO2 rose from normal (336-341 ppm, pH 8.09-8.15) to high levels (886-5,148 ppm) causing acidified conditions near the vents (pH 7.08-7.79). Only the syllid polychaete Syllis prolifera had higher abundances at the most acidified station, although a wide range of polychaetes and small crustaceans was able to settle and survive under these conditions. A few taxa (Amphiglena mediterranea, Leptochelia dubia, Caprella acanthifera) were particularly abundant at stations acidified by intermediate amounts of CO2 (pH 7. 41-7.99). These results show that increased levels of CO2 can profoundly affect the settlement of a wide range of benthic organisms. © 2010 Springer-Verlag