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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea-pig lungs.

1. Rabbit aorta contracting substance (RCS) and prostaglandins were released from guinea-pig isolated perfused lungs by gentle massage and also by infusion of Prosparol.2. RCS and prostaglandins were also released by infusion into the pulmonary artery of bradykinin, arachidonic and dihomo-gamma-linolenic acids or shock perfusate (containing RCS-releasing factor).3. Arachidonic and dihomo-gamma-linolenic acids caused a prolonged release of RCS and prostaglandins whereas bradykinin and shock perfusate gave a short-lasting output.4. RCS and prostaglandins, together with histamine were released when superfused chopped lung tissue was agitated.5. Challenge of sensitized guinea-pigs in vivo led to the release of an RCS-like substance into the carotid arterial blood.6. Intravenous injection of bradykinin into guinea-pigs also released an RCS-like substance.7. The release of RCS and prostaglandins was inhibited by aspirin or indomethacin in all experiments.8. RCS contracted all vascular tissues investigated and also rat stomach strip.9. The half-life of RCS was estimated as 1-2 minutes.

Comparison of regional and general anesthesia for carotid endarterectomy.

Two hundred twenty-one patients undergoing carotid endarterectomy were studied for morbidity and mortality. Thirty-seven had general anesthesia and 138 had regional anesthesia. The two groups were similar in preoperative risk factors and were operated on by a single surgeon and similar operative teams. Patient selection was prospective in the sense that the first 37 procedures were performed with general anesthesia and the next 184, with regional anesthesia. No significant difference in incidences of death, myocardial infarction, stroke, or transient ischemic attack was found. Hospital lengths of stay were similar. The type of anesthetic used for carotid endarterectomy should be the choice of the surgeon and operative team.

The arrangement of resources in patchy landscapes: effects on distribution, survival, and resource acquisition of chironomids.

The spatial arrangement of resources in patchy habitats influences the distribution of individuals and their ability to acquire resources. We used Chironomus riparius, a ubiquitous aquatic insect that uses leaf particles as an important resource, to ask how the dispersion of resource patches influences the distribution and resource acquisition of mobile individuals in patchy landscapes. Two experiments were conducted in replicated laboratory landscapes (38×38 cm) created by arranging sand and leaf patches in a 5×5 grid so that the leaf patches were either aggregated or uniformly dispersed in the grid. One-day-old C. riparius larvae were introduced into the landscapes in one of three densities (low, medium, high). In experiment 1, we sampled larvae and pupae by coring each patch in each landscape 3, 6, 12, or 24 days after adding larvae. In experiment 2, emerging adults were collected daily for 42 days from each patch in each landscape. In aggregated landscapes, individuals were aggregated in one patch type or the other during a particular developmental stage, but the "preferred" type changed depending on developmental stage and initial density. Adult emergence was lower by about 30% in all aggregated landscapes. In dispersed landscapes, individuals used both types of patch throughout their life cycles at all initial densities. Thus, patch arrangement influences the distribution of mobile individuals in landscapes, and it influences resource acquisition even when average resource abundance is identical among landscapes. Regardless of patch arrangement, high initial density caused accumulation of early instars in edge patches, 75% mortality of early instars, a 25% increase in development time, and a 60% reduction in adult emergence. Because mortality was extremely high among early-instar larvae in high-density treatments, we do not have direct evidence that the mechanism by which patch arrangement operates is density dependent. However, the results of our experiments strongly suggest that dispersion of resource patches across a landscape reduces local densities by making non-resource patches available for use, thereby reducing intraspecific competition.

Response of invertebrates to lotic disturbance: a test of the hyporheic refuge hypothesis.

Recovery following hydrological disturbances is usually rapid for lotic invertebrates. Stream ecologists have assumed that recovery is facilitated by behavioral migrations during floods down into the hyporheic zone (the interstitial spaces of a streambed) to seek temporary refuge from possible erosion (the "hyporheic refuge hypothesis"). We provide the first explicit test of this hypothesis by evaluating three predictions of the hypothesis. We coupled field observations of the response of meiofaunal invertebrates to floods with field and flume experiments. The study site was a sandy-bottom stream in northern Virginia. Prediction 1, that loss of fauna from a streambed during floods should be minimal as long as the depth of scour in the streambed is less than the depth of the hyporheic zone, was not supported for any taxon. For two floods which varied considerably in magnitude, 50-90% of the fauna was lost from the bed despite the fact that the depth of scour (10-30 cm) was significantly less than the total depth of the hyporheic zone (50 cm). Prediction 2, that fauna should move deeper into the bed at higher flows, was supported by field observations during only one of two floods and then only for rotifers. In flume experiments that tested for finer scale behavioral movements, significant vertical migrations were found for copepods and chironomids which moved 1.5-3.5 cm downward as mean velocity (3 cm off bottom) was increased from 5-23 cm/s. Movements down by rotifers were not found in the flume experiments. Prediction 3, that the hyporheic zone is the most important source of colonists to defaunated areas, was supported in part by field experiments. The hyporheic route was not the primary route for any taxon but it was as important for the rotifers and copepods as water column or streambed surface routes. We conclude that, even though smallscale (cm's) migrations into the streambed in response to increased flow may be observed for some taxa and the hyporheic zone may serve as a partial source of colonists following disturbances, movements down are not adequate in preventing significant losses of meiofauna during floods.

A gelatin test to detect activity and stability of proteases produced by Dichelobacter (Bacteroides) nodosus.

Previously reported tests to distinguish thermostable and thermolabile proteases of Dichelobacter nodosus used hide powder azure as a test substrate. This paper describes an alternative test for protease stability using gelatin, an inexpensive and convenient substrate. The test required less equipment and time than the hide powder tests, and simplified the testing of multiple samples. Proteases from 2965 isolates of D. nodosus from samples collected as part of a footrot eradication scheme were tested using the gelatin method, 1707 produced thermostable, and 1258 produced thermolabile protease. Production of thermostable protease was used to identify isolates of D. nodosus which had the potential to cause the virulent form of ovine footrot. Comparisons were made with a hide powder test on 47 isolates. Further characterisation of all proteases was undertaken using polyacrylamide gel electrophoresis. Isoenzyme patterns of thermostable protease producing isolates were identified as S1 (1688 isolates) and S2 (19) whilst thermolabile protease producing isolates showed patterns U1 (1104 isolates), U2 (40), U3 (32), U4 (47), U5 (6), U6 (28) and S1 (1).

Comparison of gene probe and conventional methods for the differentiation of ovine footrot isolates of Dichelobacter nodosus.

In a collaborative study that involved four Australian veterinary diagnostic laboratories a gene probe test based on the recombinant plasmids pJIR318, pJIR314B, and pJIR313, which contain genomic vap or vrl regions, was compared with conventional tests used for the differential diagnosis of ovine footrot. A total of 771 clinical dichelobacter nodosus isolates were tested and designated as belonging to one of several gene probe categories. The results showed that 87% of the virulent isolates belonged to gene probe category 1, compared to only 6% of the benign isolates. It was concluded that there was good correlation between the gene probe test and the virulence designation of these isolates as well as the results of elastase, gelatin-gel and protease isoenzyme tests. Furthermore, the gene probe test was converted to a polymerase chain reaction (PCR)-based test. It is suggested that diagnostic laboratories consider carrying out both this PCR test and tests based on the extracellular proteases of D. nodosus.

Sepsis-induced depression of phagocytosis in experimental canine peritonitis.

Experimental canine peritonitis was produced in 14 dogs by appendiceal ligation. Phagocytic activity in blood and peritoneal fluid was examined during the peritonitis and following surgical intervention. In nine dogs, the gangrenous appendix was resected after 43 hours, the peritoneal cavity was irrigated, and fibrinous exudate debrided. The remaining five dogs were not tested. Leukocytes in blood and peritoneal fluid were counted preligation and at 24, 43, 46, and 55 hours postligation. Polymorphonuclear leukocytes (PMNs) predominated. Phagocytosis and killing of Candida tropicalis by blood and peritoneal PMNs were assayed by a coverslip method. As sepsis progressed, phagocytosis by blood PMNs declined and at 43 hours was 60 per cent of the preoperative level. After resection of the gangrenous appendix, phagocytic activity returned to 90 per cent of preoperative levels at 12 hours postresection. Peritoneal PMNs exhibited a similar, but more depressed pattern of phagocytic activity. Phagocytosis in five sham-operated dogs was unchanged. Thus, phagocytosis by blood and peritoneal PMNs was depressed in peritonitis and was restored following surgical treatment.

Inferior vena cava occlusion secondary to aortic aneurysm.

A case of inferior vena caval thrombosis secondary to aortic aneurysm is presented with management guidelines. CT scanning, as well as conventional venography and arteriography, is very useful in understanding this process preoperatively. Intraoperative management should prevent pulmonary embolism and should anticipate the possibility of blood loss in excess of that which usually occurs with an uncomplicated aneurysm repair. Detailed review of the literature reveals this is a rare complication of aneurysm disease and a potentially lethal one.