Plasma electron acceleration driven by a long-wave-infrared laser.

Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses of wavelength λL ~ 1 µm. Longer-λL lasers can potentially accelerate higher-quality bunches, since they require less power to drive larger wakes in less dense plasma. Here, we report on a self-injecting plasma accelerator driven by a long-wave-infrared laser: a chirped-pulse-amplified CO2 laser (λL ≈ 10 µm). Through optical scattering experiments, we observed wakes that 4-ps CO2 pulses with < 1/2 terawatt (TW) peak power drove in hydrogen plasma of electron density down to 4 × 1017 cm-3 (1/100 atmospheric density) via a self-modulation (SM) instability. Shorter, more powerful CO2 pulses drove wakes in plasma down to 3 × 1016 cm-3 that captured and accelerated plasma electrons to relativistic energy. Collimated quasi-monoenergetic features in the electron output marked the onset of a transition from SM to bubble-regime acceleration, portending future higher-quality accelerators driven by yet shorter, more powerful pulses.

Efficacy of a dietitian-led very low calorie diet (VLCD) based model of care to facilitate weight loss for obese patients prior to elective, non-bariatric surgery.

BACKGROUND: Elective surgery in obese adults carries a higher risk of post-operative infection and prolonged hospital stays, and surgeons may postpone surgery for patients with obesity until they lose weight. The present study aimed to determine the efficacy of a dietitian-led very low calorie diet (VLCD)-based model of care with respect to achieving weight loss for obese patients prior to surgery. METHODS: This mixed-methods study included a medical chart audit of patients referred to a VLCD-based model over 23 months, as well as a survey of recently treated patients and surgeons who utilised the model. Preoperative weight loss targets were set by surgeons, and the dietitian prescribed individualised VLCD-based treatment. Efficacy was determined as weight loss considered sufficient for surgery, clinical safety of VLCD-based treatment, feasibility, and stakeholder value. Pre/post-intervention differences in clinical measures were explored by paired t-test or Wilcoxon tests as appropriate. RESULTS: Data on seventy-eight eligible patients [mean (SD) 45 (13) years, 90% female, body mass index 44.3 (6.2) kg m-2 ] demonstrated significant mean (SD) weight loss of 7.4% (5.3%) body weight (P < 0.05). Most patients (70%, n = 50/71) achieved sufficient weight loss to proceed to surgery. Fifty-six per cent of patients reported mild side effects (n = 43/77) and none led to treatment cessation. Surgeons reported VLCD-based treatment made operations easier (83%, n = 10/12) and shorter (75%, n = 9/12) and all recommended the model of care. All surveyed patients (n = 24) reported satisfaction with their VLCD-based model experience. CONCLUSIONS: A dietitian-led VLCD-based model achieved sufficient weight loss to facilitate elective surgery for most patients. The approach was feasible, highly valued by patients and surgeons, and resulted in perceived surgical benefits.

Exercise and cancer: a position statement from the Spanish Society of Medical Oncology.

Due to improvements in the number of cancer survivors and survival time, there is a growing interest in healthy behaviors, such as physical activity (PA), and their potential impact on cancer- and non-cancer-related morbidity in individuals with cancer. Commissioned by the Spanish Society of Medical Oncology (SEOM), in this review, we sought to distill the most recent evidence on this topic, focusing on the mechanisms that underpin the effects of PA on cancer, the role of PA in cancer prevention and in the prognosis of cancer and practical recommendations for clinicians regarding PA counseling. Despite the available information, the introduction of exercise programs into the global management of cancer patients remains a challenge with several areas of uncertainty. Among others, the most effective behavioral interventions to achieve long-term changes in a patient's lifestyle and the optimal intensity and duration of PA should be defined with more precision in future studies.

SEOM clinical guidelines in advanced and recurrent breast cancer (2018).

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.

Identifying physiological measures of lifetime welfare status in pigs: exploring the usefulness of haptoglobin, C- reactive protein and hair cortisol sampled at the time of slaughter.

BACKGROUND: Physiological measures indicative of the welfare status of animals during rearing could form part of an abattoir-based animal health and welfare assessment tool. A total of 66 pigs were used in this study, the aim of which was to assess how serum concentrations of haptoglobin (Hp) and C-reactive protein (CRP) (assessed in 51 pigs), and hair concentrations of cortisol (assessed in 65 pigs), measured at or close to slaughter, reflected welfare-related indicators recorded from the animal during its lifetime. These indicators were recorded at intervals between 7 and 21 weeks of age and included assigning scores for levels of tail and skin lesions, recording the presence or absence of certain health issues, and conducting qualitative behavioural assessments (QBA). RESULTS: Pigs recorded as having tail lesions during their lifetime had higher hair cortisol levels than those with no tail lesions (tail lesions: 47.87 ± 3.34 pg/mg, no tail lesions: 42.20 ± 3.29 pg/mg, P = 0.023), and pigs recorded as having moderate or severe tail lesions had higher Hp levels than those with no or mild tail lesions (moderate/severe: 1.711 mg/ml ± 0.74, none/mild: 0.731 mg/ml ±0.10, P = 0.010). Pigs recorded as being lame during their lifetime tended to have higher hair cortisol levels than non-lame pigs (lame: 52.72 pg/mg ± 3.83, not lame: 43.07 pg/mg ± 2.69, P = 0.062). QBA scores were not associated with any of the physiological measures (P > 0.05). Receiver Operator Curve (ROC) analysis was also carried out to get a better understanding of the usefulness of the physiological measures in discriminating animals that had had welfare-related issues recorded during their lifetime from those that had not. Hair cortisol was determined as having 'moderate' accuracy in discriminating pigs that were tail bitten on-farm from unbitten pigs (AUC: 0.748) while Hp and CRP were determined to have no meaningful discriminatory ability (AUC < 0.600). CONCLUSION: This research should be repeated on a larger scale, but the results suggest that hair cortisol measured at slaughter could provide insight into the welfare status of pigs during their lifetime. Hp may be a useful indicator of tail lesions in pigs. However, further research utilising a greater proportion of severely bitten pigs is required before conclusions can be drawn.

Throw caution to the wind: is refeeding syndrome really a cause of death in acute care?

BACKGROUND/OBJECTIVES: Refeeding syndrome (RFS), a life-threatening medical condition, is commonly associated with acute or chronic starvation. While the prevalence of patients at risk of RFS in hospital reportedly ranges from 0 to 80%, the prevalence and types of patients who die as a result of RFS is unknown. We aimed to measure the prevalence rate and examine the case histories of patients who passed away with RFS listed as a cause of death. SUBJECTS/METHODS: Patients were eligible for inclusion provided their death occurred within a Queensland hospital. Medical charts were reviewed, for medical, clinical and nutrition histories with results presented using descriptive statistics. RESULTS: Across 18 years (1997-2015) and ~260000 hospital deaths, five individuals (4F, 74 (37-87)yrs) were identified. No patient had a past or present diagnosis, such as anorexia nervosa, that would classify them as at high risk for RFS. RFS was not listed as the primary cause of death for any patient. No individual consumed >3400 kJ per day. Limited consensus was observed in the signs and symptoms used to diagnose RFS, although all patients experienced low levels of potassium, phosphate and/or magnesium. Eighty percent of electrolytes improved before death. CONCLUSIONS: RFS was a rare underlying cause of death, despite reported high prevalence rates of risk. Patient groups usually considered to be at high risk were not identified, suggesting a level of imprecision with the interpretation of criteria used to identify RFS risk. More detailed research is warranted to assist in the identification of those distinctly at risk of RFS.

The MUSOS (MUsic SOftware System) Toolkit: A computer-based, open source application for testing memory for melodies.

Despite numerous innovative studies, rates of replication in the field of music psychology are extremely low (Frieler et al., 2013). Two key methodological challenges affecting researchers wishing to administer and reproduce studies in music cognition are the difficulty of measuring musical responses, particularly when conducting free-recall studies, and access to a reliable set of novel stimuli unrestricted by copyright or licensing issues. In this article, we propose a solution for these challenges in computer-based administration. We present a computer-based application for testing memory for melodies. Created using the software Max/MSP (Cycling '74, 2014a), the MUSOS (Music Software System) Toolkit uses a simple modular framework configurable for testing common paradigms such as recall, old-new recognition, and stem completion. The program is accompanied by a stimulus set of 156 novel, copyright-free melodies, in audio and Max/MSP file formats. Two pilot tests were conducted to establish the properties of the accompanying stimulus set that are relevant to music cognition and general memory research. By using this software, a researcher without specialist musical training may administer and accurately measure responses from common paradigms used in the study of memory for music.

New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Evaluation of a copro-antigen ELISA to detect Fasciola hepatica infection in sheep, cattle and horses.

OBJECTIVE: To determine the specificity and sensitivity of a commercial copro-antigen ELISA for the detection of Fasciola hepatica infection in cattle and sheep and to assess the suitability of the test for use in horses. METHODS: Testing was done on more than 100 negative faecal samples from each of sheep, cattle and horses and on at least 40 positive faecal samples from each species. Positive samples were selected based on a positive sedimentation test for liver fluke eggs. Faecal samples of animals from Western Australia, which is free of liver fluke infection, served as negative controls. Specificity and sensitivity were assessed for each species using the recommended kit cut-off and also custom cut-offs specific for each species based on the mean plus 3-fold standard deviation of the mean of the negative samples for each species. RESULTS: Using the cut-off recommended by the kit manufacturer, the specificity was 100% for all species and the sensitivity was 88%, 80% and 9% for sheep, cattle and horses, respectively. Using the lower custom cut-offs for each species improved the sensitivity to 100% for sheep, 87% for cattle and 28% for horses, while maintaining the specificity above 99% for all species. CONCLUSIONS: The sensitivity of the commercial copro-antigen ELISA can be improved by using custom cut-off values for each species. With this modification, it is a suitable alternative screening test to the currently used sedimentation test for border control of sheep and cattle movement. The test is not suitable for use in horses.

Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours.

PURPOSE: To estimate the cost per skeletal-related event (SRE) in patients with bone metastases secondary to solid tumours in the Spanish healthcare setting. METHODS: Patients diagnosed with bone metastases secondary to breast, prostate or lung cancer were included in this multicentre, observational study. SREs are defined as pathologic fracture (vertebral and non-vertebral fracture), radiation to bone, spinal cord compression or surgery to bone. Health resource utilisation associated with these events (inpatient stays, outpatient, emergency room and home health visits, nursing home stays and procedures) were collected retrospectively for all SREs that occurred in the 97 days prior to enrolment and prospectively during follow-up. Unit costs were obtained from the 2010 eSalud healthcare costs database. RESULTS: A total of 93 Spanish patients with solid tumours were included (31 had breast cancer, 21 prostate cancer and 41 lung cancer), contributing a total of 143 SREs to this cost analysis. Inpatient stays (between 9.0 and 29.9 days of mean length of stay per inpatient stay by SRE type) and outpatient visits (between 1.7 and 6.4 mean visits per SRE type) were the most frequently reported types of health resources utilised. The mean cost per SRE was between 2,377.79 (radiation to bone) and 7,902.62 (spinal cord compression). CONCLUSION: SREs are associated with a significant consumption of healthcare resources that generate a substantial economic burden for the Spanish healthcare system.

The effect of slurry on skin permeability to methylene blue dye in dairy cows with and without a history of digital dermatitis.

This study aimed to determine whether there was a difference in skin permeability to methylene blue dye or skin morphology between dairy cows that differed in their susceptibility to digital dermatitis (DD) and to assess the effect of contact with slurry on skin permeability. Twenty nine dairy cows were monitored for DD during the winter housing period and classed as DD+ (previous DD infection, n = 17), or DD- (no recorded infection, n = 12). The animals were culled and a skin sample was taken from above the heel of each hind foot and frozen. Samples were later defrosted and one sample from each cow was tested for permeability, whereas the other was treated with slurry for 24 h before permeability testing. To test permeability, methylene blue dye was applied to the skin surface in a Franz diffusion cell. After 48 h, the amount of dye that had passed through the skin was estimated. The stratum corneum thickness and the density of hair follicles were determined from additional heel skin samples. Skin permeability to methylene blue dye was significantly greater for samples that had been treated with slurry but did not differ between DD+ and DD- animals. No difference was found in the stratum corneum thickness or density of hair follicles between DD+ and DD- animals. These findings imply that individual differences in general skin permeability are not a major factor in determining DD susceptibility and suggest that contact with slurry could contribute to DD infection by increasing the permeability of the skin, which may facilitate pathogen entry. Further work is required to clarify the role played by slurry in the pathogenesis of DD.

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer.

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered.

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered (AU)

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Stream insect occupancy-frequency patterns and metapopulation structure.

An understanding of the distribution patterns of organisms and the underlying factors is a fundamental goal of ecology. One commonly applied approach to visualize these is the analysis of occupancy-frequency patterns. We used data sets describing stream insect distributions from different regions of North America to analyze occupancy-frequency patterns and assess the effects of spatial scale, sampling intensity, and taxonomic resolution on these patterns. Distributions were dominated by satellite taxa (those occurring in or=90% of sites) determined the overall modality of occupancy-frequency patterns. The proportions of satellite taxa increased with spatial scale and showed positive relationships with sampling intensity (r2=0.74-0.96). Furthermore, analyses of data sets from New York (USA) showed that generic-level assessments underestimated the satellite class and occasionally shifted occupancy-frequency distributions from unimodal to bimodal. Our results indicate that, regardless of species- or generic-level taxonomy, stream insect communities are characterized by satellite species and that the proportion of satellite species increases with spatial scale and sampling intensity. Thus, niche-based models of occupancy-frequency patterns better characterize stream insect communities than metapopulation models such as the core-satellite species hypothesis.