Symposium review: Defining a pathway to climate neutrality for US dairy cattle production.

The US dairy industry has made substantial gains in reducing the greenhouse gas emission intensity of a gallon of milk. At the same time, consumer and investor interest for improved environmental benefits or reduced environmental impact of food production continues to grow. Following a trend of increasing greenhouse gas emission commitments for businesses across sectors of the economy, the US dairy industry has committed to a goal of net zero greenhouse gas emissions by 2050. The Paris Climate Accord's goal is to reduce warming of the atmosphere to less than 1.5 to 2°C based on preindustrial levels, which is different from emission goals of historic climate agreements that focus on emission reduction targets. Most of the emissions that account for the greenhouse gas footprint of a gallon of milk are from the short-lived climate pollutant CH4, which has a half-life of approximately 10 yr. The relatively new accounting system Global Warming Potential Star and the unit CO2 warming equivalents gives the industry the appropriate metrics to quantify their current and projected warming impact on future emissions. Incorporating this metric into potential future emissions pathways can allow the industry to understand the magnitude of emissions reductions needed to no longer contribute additional warming. Deterministic modeling was performed across the dairy industry's emission areas of enteric fermentation, manure management, feed production, and other upstream emissions necessary for dairy production. By reducing farm-level absolute emissions by 23% based on current levels, there is the opportunity for the US dairy industry to realize climate neutrality within the next few decades.

Chronic prepartum light-dark phase shifts in cattle disrupt circadian clocks, decrease insulin sensitivity and mammary development, and are associated with lower milk yield through 60 days postpartum.

Circadian and metabolic systems are interlocked and reciprocally regulated. To determine if the circadian system regulates glucose homeostasis and mammary development, the function of the circadian system was disrupted by exposing cattle to chronic light-dark cycle phase shifts from 5 wk before expected calving (BEC) to parturition. Multiparous Holstein cows were exposed to 16 h of light and 8 h of dark (CON, n = 8) or phase shifting (PS, n = 8) the light cycle 6 h every 3 d beginning 35 d BEC. After calving, both treatments were exposed to CON lighting. Mammary biopsies were taken at 21 d BEC and 21 d in milk (DIM), and histological analysis indicated PS treatment decreased the ratio of lumen to alveolar area and percentage of proliferating epithelial cells in the prepartum period. Intravenous glucose tolerance test was performed at 14 d BEC and 7 DIM by administering 50% dextrose. Blood glucose, ß-hydroxybutyrate, insulin, and nonesterified fatty acids were consequently measured over 3 h. At 14 d BEC no treatment differences were observed in baseline glucose or insulin. Treatment had no effect on blood glucose or glucose area under the curve at 14 d BEC and 7 DIM. Insulin area under the curve was higher in PS versus CON at 14 d BEC and 7 DIM. The PS cows produced less milk than CON cows through 60 DIM (40.3 vs. 42.6 kg/d). Exposure to chronic light-dark PS in late gestation decreased mammary development and increased insulin resistance in periparturient cows, which may have caused subsequent lower milk yield.

The role of preoperative instructions in parents' understanding of preoperative fasting for outpatient pediatric urology procedures.

PURPOSE: To assess the impact of modifications in preoperative instructions on parental understanding of preoperative fasting guidelines. METHODS: A prospective postoperative parental survey was conducted to assess parental understanding of preoperative fasting requirements in patients undergoing surgery before and after institution of instructions that included visual aids. Data regarding demographics, procedure type, and time to surgery from preoperative visit were also captured. Survey data were compared between pre- and post-intervention groups using Chi-squared tests for categorical variables and Wilcoxon rank sum test for continuous variables. RESULTS: 173 parents in the pre-intervention group and 162 parents in the post-intervention group were included in the analysis. Parent identification of aspiration risk as the reason for fasting almost doubled after intervention (72.2% vs. 38.2%). There was some evidence of demographic differences between groups; however, in an adjusted model, there was strong evidence (p < 0.001) that parents in the post-intervention group were more likely to identify aspiration as the reason for preoperative fasting (OR 4.73; 95% CI 2.93-7.63). CONCLUSIONS: Addition of visual aids in preoperative instructions was associated with improvement in parents' understanding of the rationale behind preoperative fasting instructions. Further studies are needed to determine whether improved understanding is associated with improved adherence.

[The German version of the Bath Body Perception Disturbance Scale (BBPDS-D) : Translation, cultural adaptation and linguistic validation on patients with complex regional pain syndrome]. / Die deutsche Version der Bath Body Perception Disturbance Scale (BBPDS-D) : Übersetzung, kulturelle Anpassung und linguistische Validierung an Patienten mit komplexem regionalem Schmerzsyndrom.

BACKGROUND: Besides the classical clinical manifestations, body perception disturbances are common among patients with complex regional pain syndrome (CRPS). The Bath Body Perception Disturbance Scale (BBPDS) represents a useful tool to assess these changes in CRPS patients; however, to date no validated German version is available. OBJECTIVE: The aim of this study was to translate the BBPDS into German, to perform a cross-cultural adaptation and linguistic validation in patients with acute (symptoms <3 months) and stable (symptoms ≥3 months) CRPS. MATERIAL AND METHODS: The original English version of the BBPDS was translated into German according to published guidelines (translation and back translation) and tested on 56 patients (mean age 50.9 ± 13.1 years) with acute (n = 28) or stable (n = 28) CRPS. RESULTS: The relative reliability, intraclass correlation and test-retest reliability were excellent overall and in the groups with acute and stable CRPS. The smallest detectable change was at 10 points. In the test-retest 48 points lay within the 95% confidence interval and visual inspection showed no tendency towards heteroscedasticity. Spearman's ρ­coefficient values showed no correlation between the total score of the BBPDS-D with the numerical rating scale (NRS, ρ = -0.19) and the EuroQol-5 D (ρ = 0.16). There were no significant differences between patients with acute and stable CRPS (p = 0.412). There were also no floor or ceiling effects. CONCLUSION: This German translation and cross-cultural adaptation of the original English version of the BBPDS is a valid instrument to assess body perception disturbances in German speaking CRPS patients. Future research should further assess the impact of body perception disturbance on treatment outcome and prognosis.

Cancer-related pain management: A review of knowledge and attitudes of healthcare professionals.

Cancer-related pain (CRP) is common and many patients continue to experience pain in spite of advances in pain management modalities. The lack of knowledge, inadequate assessment of CRP and/or organisational factors, such as lack of time due to heavy workload, can be a barrier to effective pain management of healthcare professionals. The purpose was to examine the evidence with regard to the knowledge and attitudes towards practice of healthcare professionals in relation to CRP management. A search of the literature (1999-2015) was conducted searching databases and journals including CINAHL, MEDLINE, PsycINFO, PubMed, Science Direct and Wiley-Blackwell. The initial search revealed a total of 99 articles and following removal of those that did not meet the inclusion criteria, 19 articles were included in the final review. Recognition of the widespread under treatment of CRP has prompted recent corrective efforts in terms of education from healthcare professionals, however, there is a continuing deficit in healthcare professionals' knowledge with regard to CRP management and indicated that healthcare professionals still have negative attitudes that hinder the delivery of quality care to patients suffering from CRP. Further research on how and where education on this topic should be delivered is required.

Research prioritization of men's health and urologic diseases.

OBJECTIVES: We sought to determine whether disease representation in the Cochrane Database of Systematic Reviews (CDSR) reflects disease burden, measured by the Global Burden of Disease (GBD) Study as disability-adjusted life-years (DALYs). MATERIALS AND METHODS: Two investigators performed independent assessment of ten men's health and urologic diseases (MHUDs) in CDSR for systematic review and protocol representation, which were compared with percentage of total 2010 DALYs for the ten conditions. Data were analyzed for correlation using Spearman rank analysis. RESULTS: Nine of ten MHUDs were represented by at least one CDSR review. There was a poor and statistically insignificant positive correlation between CDSR representation and disease burden (rho = 0.42, p = 0.23). CDSR representation was aligned with disease burden for three conditions, greater than disease burden for one condition, and less than disease burden for six conditions. CONCLUSIONS: These results yield high-quality estimates to inform future research prioritization for MHUDs. While prioritization processes are complex and multi-faceted, disease burden should be strongly considered. Awareness of research priority setting has the potential to minimize research disparities on a global scale.

Enhanced neural response to anticipation, effort and consummation of reward and aversion during bupropion treatment.

BACKGROUND: We have previously shown that the selective serotonergic reuptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic reuptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear. METHOD: Seventeen healthy volunteers (9 female, 8 male) received 7 days bupropion (150 mg/day) and 7 days placebo treatment, in a double-blind crossover design. Our functional magnetic resonance imaging task consisted of three phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes. RESULTS: Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase. CONCLUSIONS: Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect.

Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.

STUDY QUESTION: Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? SUMMARY ANSWER: T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. WHAT IS KNOWN ALREADY: Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. STUDY DESIGN, SIZE, DURATION: This laboratory-based study used human decidua from first (8-11 weeks; n = 18) and second (12-16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10-) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel(®) was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRß1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different cell isolates were unaffected by T3 so changes in cell numbers could not account for any observed effects. In the first trimester, T3 decreased VEGF-A secretion by total decidual cells (P < 0.05) and increased angiopoietin-2 secretion by stromal-depleted cells (P < 0.05) but in the second trimester total decidual cells showed only increased angiogenin secretion (P < 0.05). In the first trimester, T3 reduced IL-10 secretion by total decidual cells (P < 0.05), and reduced granulocyte macrophage colony stimulating factor (P < 0.01), IL-8 (P < 0.05), IL-10 (P < 0.01), IL-1ß (P < 0.05) and monocyte chemotactic protein -1 (P < 0.001) secretion by macrophages, but increased tumour necrosis factor-α secretion by stromal-depleted cells (P < 0.05) and increased IL-6 by uNK cells (P < 0.05). In contrast, in the second trimester T3 increased IL-10 secretion by total decidual cells (P < 0.01) but did not affect cytokine secretion by uNK cells and macrophages. Conditioned media from first trimester T3-treated total decidual cells and macrophages did not alter EVT invasion compared with untreated controls. Thus, treatment of decidual cells with T3 resulted in changes in both angiogenic growth factor and cytokine secretion in a cell type-specific and gestational age-dependent manner, with first trimester decidual macrophages being the most responsive to T3 treatment, but these changes in decidual cell secretome did not affect EVT invasion in vitro. LIMITATIONS, REASONS FOR CAUTION: Our results are based on in vitro findings and we cannot be certain if a similar response occurs in human pregnancy in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Optimal maternal thyroid hormone concentrations could play a critical role in maintaining a balanced inflammatory response in early pregnancy to prevent fetal immune rejection and promote normal placental development through the regulation of the secretion of critical cytokines and angiogenic growth factors by human decidual cells. Our data suggest that there is an ontogenically determined regulatory 'switch' in T3 responsiveness between the first and second trimesters, and support the notion that the timely and early correction of maternal thyroid dysfunction is critical in influencing pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): This study is funded by Wellbeing of Women (RG/1082/09 to S.Y.C., M.D.K., J.A.F., L.S.L., G.E.L.) and Action Medical Research - Henry Smith Charity (SP4335 to M.D.K., S.Y.C., L.S.L., J.A.F.). The authors have no conflicts of interest to disclose.

Healthcare professionals' knowledge, understanding and confidence to manage chronic pain after cancer treatment: A UK survey.

INTRODUCTION: Healthcare professionals are vital in preparing people living with and beyond cancer about the risks of chronic pain after cancer treatment. To do so, healthcare professionals need to be knowledgeable and confident about chronic pain after cancer treatment, yet little is known about their understanding or confidence of this common long-term and late side effect of cancer treatment. AIM: To identify healthcare professionals' knowledge and understanding of chronic pain after cancer treatment and consider how confident they are to inform, listen and signpost people living with and beyond cancer to appropriate information and support. METHOD: A cross sectional online survey was distributed to healthcare professionals in the UK via cancer and primary care networks, cancer alliances and social media. The survey consisted of four domains: 1) knowledge and understanding, 2) information and support, 3) confidence and 4) barriers. Quantitative data were analysed with descriptive statistics and free text comments were analysed using qualitative content analysis. RESULTS: Healthcare professionals reported limited knowledge and understanding of chronic pain after cancer treatment. Healthcare professionals lacked confidence to talk to people about chronic pain after cancer treatment and viewed their lack of knowledge as a barrier. Additional barriers included 'Limited service provision', 'Conflict between services', 'Not my role' and 'Challenges in diagnosing chronic pain in cancer survivors'. CONCLUSION: Chronic pain after cancer can be a significant issue for those living with and beyond cancer, yet healthcare professionals report limited knowledge of it or understanding of the impact. More education is needed to increase healthcare professionals' knowledge and confidence in chronic pain after cancer treatment.

Comparison of several classical density functional theories for the adsorption of flexible chain molecules into cylindrical nanopores.

Adsorption of flexible oligomers into narrow cylindrical pores has been studied by means of several versions of classical density functional theory (CDFT) and Monte Carlo simulation. The adsorption process is interesting to study due to the competition between the entropic depletion of oligomers from the pores and the wall-oligomer attraction. It is also challenging to describe using current CDFTs, which tend to overestimate the amount of the adsorbed fluid. From a comparison of several different CDFT approaches, we find that this is due to the assumption of ideal or freely jointed chain conformations. Moreover, it is demonstrated that it is impossible to obtain a reasonable description of the adsorption isotherms without taking into account accurate contact values in the distribution functions describing the structure of the reference monomer fluid. At low densities, more accurate result are obtained in comparison with Monte Carlo simulation data when accurate contact values are incorporated into the theory rather than the more commonly used hard-sphere contact value. However, even the CDFT with accurate contact values still overestimates the amount of the adsorbed fluid due to the ideal or freely jointed chain approximation, used for the description of chain conformations in most CDFT approaches. We find that significant improvement can achieved by employing self-consistent field theory, which samples self-avoiding chain conformations and decreases the number of possible chain conformations, and, consequently, the amount of the adsorbed fluid.

Female cricket pace bowling: kinematic and anthropometric relationships with ball release speed.

Background: Despite an increase in the professionalism and participation of female cricket, the coaching of female pace bowling is still reliant on male-derived knowledge. Objectives: To investigate the association between key male-derived kinematic and anthropometric parameters and ball release speed (BRS) in female pace bowlers. Methods: Eleven female pace bowlers participated in this study. BRS, and four anthropometric and five kinematic parameters were determined. Stepwise linear regression and Pearson Product Moment correlations were used to identify anthropometric and kinematic parameters linked to BRS. Results: The best predictor of BRS explaining 89% of the observed variance was the bowling shoulder angle at ball release. The best anthropometric predictor of BRS was height explaining 53% of the observed variance. Other parameters correlated with BRS included: run-up speed (r = 0.75, p = 0.013) and arm length (r = 0.61, p = 0.046). When height was controlled for, the front knee angle at front foot contact was also correlated to BRS (r = 0.68, p = 0.044). No relationship was found between trunk flexion and BRS. Conclusion: Faster BRS were characterised by faster run-up speeds, straighter front knees, and delayed arm circumduction similar to male pace bowlers. The lack of relationship between trunk flexion and BRS may highlight female pace bowlers adopting a bowling technique where BRS is contributed to by trunk rotation as well as trunk flexion. This knowledge is likely to be useful in the talent identification and coaching of female pace bowlers.

A novel method of determining the active drag profile in swimming via data manipulation of multiple tension force collection methods.

A novel method aimed at evaluating the active drag profile during front-crawl swimming is proposed. Fourteen full trials were conducted with each trial using a stationary load cell set-up and a commercial resistance trainer to record the tension force in a rope, caused by an athlete swimming. Seven different stroke cycles in each experiment were identified for resampling time dependent data into position dependent data. Active drag was then calculated by subtracting resistance trainer force data away from the stationary load cell force data. Mean active drag values across the stroke cycle were calculated for comparison with existing methods, with mean active drag values calculated between 76 and 140 N depending on the trial. Comparing results with established active drag methods, such as the Velocity Perturbation Method (VPM), shows agreement in the magnitude of the mean active drag forces. Repeatability was investigated using one athlete, repeating the load cell set-up experiment, indicating results collected could range by 88 N depending on stroke cycle position. Variation in results is likely due to inconsistencies in swimmer technique and power output, although further investigation is required. The method outlined is proposed as a representation of the active drag profile over a full stroke cycle.

Transport time after combat-related injury and patient-reported outcomes among US service members.

INTRODUCTION: The 'golden hour' is a universal paradigm that suggests trauma patients have lower morbidity and mortality when provided with medical care within 1 hour after injury. The objective of this study was to examine whether transport time from point of injury to a military treatment facility (MTF) in-theatre was associated with patient-reported outcomes, such as post-traumatic stress disorder (PTSD), depression and quality of life (QOL), among US service members with combat-related injury. METHODS: Participants were injured between March 2003 and March 2016 and completed standardised assessments of PTSD, depression and QOL for theWounded Warrior Recovery Project (WWRP) between January 2013 and November 2017. Multivariable regressions were used to assess the relationship between transport time (≤1 hour or >1 hour from injury to MTF) and positive screens for PTSD and depression, and QOL, respectively.Overall, 45.6% of participants (n=879) arrived at an MTF within 1 hour postinjury. About 8 years passed between when participants were injured on deployment and when they completed their first WWRP assessment. Approximately 48% of participants screened positive for PTSD and 51.3% for depression, with a mean QOL score of 0.513 (SD=0.150). After adjusting for covariates, transport time was not significantly associated with PTSD (OR 1.04, 95% CI 0.79 to 1.38; p=0.77), depression (OR 0.92, 95% CI 0.69 to 1.21; p=0.55) or QOL (ß=0.009; p=0.38). CONCLUSION: Transport time was not associated with patient-reported outcomes among US service members with combat-related injury. These findings are important as we seek to understand how combat casualties may be affected by extended medical evacuation or transport times anticipated in future expeditionary operations.

A Simulation Study of the Self-Assembly of Coarse-Grained Skin Lipids.

Computer simulations are an attractive means by which to probe the self-assembly and molecular level organization of lipids in biological membranes. In this work, we study a simple skin lipid system to demonstrate the ability of the coarse-grained models used for fatty acids, cholesterol, and water to self-assemble, thus validating the models for use in further studies of the complex lipid mixtures found in the outermost layer of the skin. Specifically, the ability of the models to predict the correct self-assembled structures from molecular dynamics simulations is compared against those seen experimentally and from all-atom simulations of preassembled bilayers. The nature of the molecular interactions and their roles in the self-assembly process is elucidated and heuristics for self-assembly established. Additionally, the coarse-grained models have been used to characterize the effect of varying cholesterol composition on bilayer properties and the mechanism of bilayer destabilization by short and long chain fatty acids in the presence of cholesterol.

The pituitary tumor transforming gene in thyroid cancer.

The pituitary tumor transforming gene (PTTG) is a multifunctional proto-oncogene that is over-expressed in various tumors including thyroid carcinomas, where it is a prognostic indicator of tumor recurrence. PTTG has potent transforming capabilities in vitro and in vivo, and many studies have investigated the potential mechanisms by which PTTG contributes to tumorigenesis. As the human securin, PTTG is involved in critical mechanisms of cell cycle regulation, whereby aberrant expression induces aneuploidy. PTTG may further contribute to tumorigenesis through its role in DNA damage response pathways and via complex interactions with hormones and growth factors. Furthermore, PTTG over-expression negatively impacts upon the efficacy of radioiodine therapy in thyroid cancer, through repression of expression and function of the sodium iodide symporter. Given its various roles at all disease stages, PTTG appears to be an important oncogene in thyroid cancer. This review discusses the current knowledge of PTTG with particular focus on its role in thyroid cancer.

The expression of thyroid hormone transporters in the human fetal cerebral cortex during early development and in N-Tera-2 neurodifferentiation.

Associations of neurological impairment with mutations in the thyroid hormone (TH) transporter, MCT8, and with maternal hypothyroxinaemia, suggest that THs are crucial for human fetal brain development. It has been postulated that TH transporters regulate the cellular supply of THs within the fetal brain during development. This study describes the expression of TH transporters in the human fetal cerebral cortex (7­20 weeks gestation) and during retinoic acid induced neurodifferentiation of the human N-Tera-2 (NT2) cell line, in triiodothyronine (T3) replete and T3-depleted media. Compared with adult cortex, mRNAs encoding OATP1A2, OATP1C1, OATP3A1 variant 2, OATP4A1, LAT2 and CD98 were reduced in fetal cortex at different gestational ages, whilst mRNAs encoding MCT8, MCT10, OATP3A1 variant 1 and LAT1 were similar. From the early first trimester, immunohistochemistry localised MCT8 and MCT10 to the microvasculature and to undifferentiated CNS cells. With neurodifferentiation, NT2 cells demonstrated declining T3 uptake, accompanied by reduced expressions of MCT8, LAT1, CD98 and OATP4A1. T3 depletion significantly reduced MCT10 and LAT2 mRNA expression at specific time points during neurodifferentiation but there were no effects upon T3 uptake, neurodifferentiation marker expression or neurite lengths and branching. MCT8 repression also did not affect NT2 neurodifferentiation. In conclusion, many TH transporters are expressed in the human fetal cerebral cortex from the first trimester, which could regulate cellular TH supply during early development. However, human NT2 neurodifferentiation is not dependent upon T3 or MCT8 and there were no compensatory changes to promote T3 uptake in a T3-depleted environment.

An infrared flash contemporaneous with the gamma-rays of GRB 041219a.

The explosion that results in a cosmic gamma-ray burst (GRB) is thought to produce emission from two physical processes: the central engine gives rise to the high-energy emission of the burst through internal shocking, and the subsequent interaction of the flow with the external environment produces long-wavelength afterglows. Although observations of afterglows continue to refine our understanding of GRB progenitors and relativistic shocks, gamma-ray observations alone have not yielded a clear picture of the origin of the prompt emission nor details of the central engine. Only one concurrent visible-light transient has been found and it was associated with emission from an external shock. Here we report the discovery of infrared emission contemporaneous with a GRB, beginning 7.2 minutes after the onset of GRB 041219a (ref. 8). We acquired 21 images during the active phase of the burst, yielding early multi-colour observations. Our analysis of the initial infrared pulse suggests an origin consistent with internal shocks.

Issues for researchers to consider when using health-related quality of life outcomes in cancer research.

Maintaining quality of life for patients with cancer is a key factor when developing services related to diagnosis, treatment, recovery and/or terminal care. This paper questions whether health-related quality of life (HRQoL) is an appropriate measure of quality of life given that it does not assess factors reported by patients as being most influential, e.g. contact with family and social/cultural interaction. Ambiguity related to the definition and understanding of anxiety, depression and distress as outcomes commonly used by clinicians and researchers when measuring HRQoL in cancer research is also addressed by this paper. The findings of many cancer studies are interpreted and presented on very broad and poorly defined concepts thus preventing the development of a coherent and true understanding of how these outcomes influence quality of life for cancer patients. The authors of this paper conclude that the documentation and clear explanation of the concepts underpinning the choice of instrument and study design is essential but also the inclusion of outcomes related to social support and interaction would provide a more accurate account of quality of life issues in cancer research.

Convergent evolution of pain-inducing defensive venom components in spitting cobras.

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

A structurally relevant coarse-grained model for cholesterol.

Detailed atomistic computer simulations are now widely used to study biological membranes, including increasingly mixed lipid systems that involve, for example, cholesterol, which is a key membrane lipid. Typically, simulations of these systems start from a preassembled bilayer because the timescale on which self-assembly occurs in mixed lipid systems is beyond the practical abilities of fully atomistic simulations. To overcome this limitation and study bilayer self-assembly, coarse-grained models have been developed. Although there are several coarse-grained models for cholesterol reported in the literature, these generally fail to account explicitly for the unique molecular features of cholesterol that relate to its function and role as a membrane lipid. In this work, we propose a new coarse-grained model for cholesterol that retains the molecule's unique features and, as a result, can be used to study crystalline structures of cholesterol. In the development of the model, two levels of coarse-graining are explored and the importance of retaining key molecular features in the coarse-grained model that are relevant to structural properties is investigated.