Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer.

BACKGROUND: To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate. METHODS: We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned transperineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer. RESULTS: Overall, 34 patients with a mean age of 65 years (s.d.=±6) and a median PSA of 6.1 ng ml(-1) (interquartile range (IQR)= 4.3-7.7) were included. Nine (26%), 24 (71%) and 1 (3%) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range 1-24), 12 grade 1 and 10 grade 2 complications occurred. No patient had grade >/= 3 complication. From a functional point of view, 100% (24/24) patients were continent and potency was preserved in 95% (19/20) men potent before treatment. The volume of ablation was a median 12 ml (IQR=5.6-14.5 ml) with the median PSA after 6 months of 3.4 ng ml(-1) (IQR=1.9-4.8 ng ml(-1)). MpMRI showed suspicious residual disease in six patients, of whom four (17%) underwent another form of local treatment. CONCLUSIONS: Focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.

Energy balance in elderly patients after surgery for a femoral neck fracture.

To study energy and protein balances in elderly patients after surgery, spontaneous energy and protein intake and resting energy expenditure (REE) were measured in 20 elderly female patients with a femoral neck fracture (mean age 81 +/- 4, SD, range 74-87 years; weight 53 +/- 8, range 42-68 kg) during a 5-6 day period following surgery. REE, measured over 20-40 min by indirect calorimetry using a ventilated canopy, averaged 0.98 +/- 0.15 kcal/min on day 3 and decreased to 0.93 +/- 0.15 kcal/min on day 8-9 postsurgery (p less than 0.02). REE was positively correlated with body weight (r = 0.69, p less than 0.005). Mean REE extrapolated to 24 hr (24-REE) was 1283 +/- 194 kcal/day. Mean daily food energy intake measured over the 5-day follow-up period was 1097 +/- 333 kcal/day and was positively correlated with 24-REE (r = 0.50, p less than 0.05). Daily energy balance was -235 +/- 351 kcal/day on day 3 (p less than 0.01 vs zero) and -13 +/- 392 kcal/day on day 8-9 postsurgery (NS vs zero) with a mean over the study period of -185 +/- 289 kcal/day (p less than 0.01 vs zero). When an extra 100 kcal/day was allowed for the energy cost of physical activity, mean daily energy balance over the 5-day study period was calculated to be -285 +/- 289 kcal/day (p less than 0.01 vs zero). Measurements of total 24-hr urinary nitrogen (N) excretion were obtained in a subgroup of 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat intake and adiposity in 8 to 11-year-old obese children.

OBJECTIVE: To investigate the relationships between diet composition, body composition, and macronutrient oxidation at rest in obese and non-obese children. DESIGN: Cross-sectional study on fat intake, adiposity and postabsorptive macronutrients oxidation rates. SUBJECTS: 82 prepubertal (age: 9.1 +/- 1.1 y) children, 30 obese (FM = 32.6 +/- 6.1%) and 52 non-obese (FM = 15.6 +/- 5.1%). MEASUREMENTS: Subcutaneous skinfold thickness for body composition, diet history for energy and nutrient intake, indirect calorimetry for resting metabolic rate (RMR) and RQ measurement. RESULTS: Energy intake (EI) was comparable in obese and non-obese children. Adjusted for RMR by ANCOVA, using RMR as the covariate, EI was significantly lower in obese than in non-obese children indicating either a blunted physical activity or a systematic underestimation of EI. Protein and carbohydrate intakes expressed as a percentage of total energy intake (%EI) were not significantly different in the two groups. Lipid intake (%EI) was slightly but significantly higher in the obese than in the non-obese group either unadjusted or adjusted for RMR by ANCOVA. The postabsorptive RQ was significantly lower in obese than in non-obese children. In the total group, %FM was weakly but significantly correlated to lipid intake (%EI). CONCLUSION: Obese prepubertal children have a higher relative fat intake than non-obese children and their FM is associated with this factor. The lower postabsorptive RQ of obese children may indicate a compensatory mechanism to achieve fat equilibrium by enhanced fat oxidation.

Long-term measurements of energy expenditure in humans using a respiration chamber.

There is a need to measure energy expenditure in man for a period of 24 h or even several days. The respiration chamber offers a unique opportunity to reach this goal. It allows the study of energy and nutrient balance; from the latter, acute changes in body composition can be obtained. The respiration chamber built in Lausanne is an air-tight room (5 m long, 2.5 m wide, and 2.5 m high) which forms an open circuit ventilated indirect calorimeter. The physical activity of the subject inside the chamber is continuously measured using a radar system based on the Doppler effect. Energy expenditure of obese and lean women was continuously measured over 24 h and diet-induced thermogenesis was assessed by using an approach which allows one to subtract the energy expended for physical activity from the total energy expenditure. Expressed in absolute terms, total energy expenditure was more elevated in the obese than in the lean controls. Basal metabolic rate was also higher in the obese than in the controls, but diet-induced thermogenesis was found to be blunted in the obese. In a second study, the effect of changing the carbohydrate/lipid content of the diet on fuel utilization was assessed in young healthy subjects with the respiration chamber. After a 7-day adaptation to a high-carbohydrate low-fat diet, the fuel mixture oxidized matched the change in nutrient intake. A last example of the use of the respiration chamber is the thermogenic response and changes in body composition due to a 7-day overfeeding of carbohydrate. Diet-induced thermogenesis was found to be 27%; on the last day of overfeeding, carbohydrate balance was reached by oxidation of 50% of the carbohydrate intake, the remaining 50% being converted into lipid.

Genetic variability of the mTOR pathway and prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

The mTOR (mammalian target of rapamycin) signal transduction pathway integrates various signals, regulating ribosome biogenesis and protein synthesis as a function of available energy and amino acids, and assuring an appropriate coupling of cellular proliferation with increases in cell size. In addition, recent evidence has pointed to an interplay between the mTOR and p53 pathways. We investigated the genetic variability of 67 key genes in the mTOR pathway and in genes of the p53 pathway which interact with mTOR. We tested the association of 1,084 tagging SNPs with prostate cancer risk in a study of 815 prostate cancer cases and 1,266 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). We chose the SNPs (n = 11) with the strongest association with risk (p<0.01) and sought to replicate their association in an additional series of 838 prostate cancer cases and 943 controls from EPIC. In the joint analysis of first and second phase two SNPs of the PRKCI gene showed an association with risk of prostate cancer (ORallele = 0.85, 95% CI 0.78–0.94, p = 1.3×10−3 for rs546950 and ORallele = 0.84, 95% CI 0.76–0.93, p = 5.6×10−4 for rs4955720). We confirmed this in a meta-analysis using as replication set the data from the second phase of our study jointly with the first phase of the Cancer Genetic Markers of Susceptibility (CGEMS) project. In conclusion, we found an association with prostate cancer risk for two SNPs belonging to PRKCI, a gene which is frequently overexpressed in various neoplasms, including prostate cancer.

Compliance with dietary and nutrient recommendations in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada cohort at recruitment

BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.

Devolatilization-induced pressure build-up: Implications for reaction front movement and breccia pipe formation

Generation of fluids during metamorphism can significantly influence the fluid overpressure, and thus the fluid flow in metamorphic terrains. There is currently a large focus on developing numerical reactive transport models, and with it follows the need for analytical solutions to ensure correct numerical implementation. In this study, we derive both analytical and numerical solutions to reaction-induced fluid overpressure, coupled to temperature and fluid flow out of the reacting front. All equations are derived from basic principles of conservation of mass, energy and momentum. We focus on contact metamorphism, where devolatilization reactions are particularly important owing to high thermal fluxes allowing large volumes of fluids to be rapidly generated. The analytical solutions reveal three key factors involved in the pressure build-up: (i) The efficiency of the devolatilizing reaction front (pressure build-up) relative to fluid flow (pressure relaxation), (ii) the reaction temperature relative to the available heat in the system and (iii) the feedback of overpressure on the reaction temperature as a function of the Clapeyron slope. Finally, we apply the model to two geological case scenarios. In the first case, we investigate the influence of fluid overpressure on the movement of the reaction front and show that it can slow down significantly and may even be terminated owing to increased effective reaction temperature. In the second case, the model is applied to constrain the conditions for fracturing and inferred breccia pipe formation in organic-rich shales owing to methane generation in the contact aureole.

Separating the contribution of glucocorticoids and wakefulness to the molecular and electrophysiological correlates of sleep homeostasis.

Study Objectives: The sleep-deprivation-induced changes in delta power, an electroencephalographical correlate of sleep need, and brain transcriptome profiles have importantly contributed to current hypotheses on sleep function. Because sleep deprivation also induces stress, we here determined the contribution of the corticosterone component of the stress response to the electrophysiological and molecular markers of sleep need in mice. Design: N/A Settings: Mouse sleep facility. Participants: C57BL/6J, AKR/J, DBA/2J mice. Interventions: Sleep deprivation, adrenalectomy (ADX). Measurements and Results: Sleep deprivation elevated corticosterone levels in 3 inbred strains, but this increase was larger in DBA/2J mice; i.e., the strain for which the rebound in delta power after sleep deprivation failed to reach significance. Elimination of the sleep-deprivation-associated corticosterone surge through ADX in DBA/2J mice did not, however, rescue the delta power rebound but did greatly reduce the number of transcripts affected by sleep deprivation. Genes no longer affected by sleep deprivation cover pathways previously implicated in sleep homeostasis, such as lipid, cholesterol (e.g., Ldlr, Hmgcs1, Dhcr7, -24, Fkbp5), energy and carbohydrate metabolism (e.g., Eno3, G6pc3, Mpdu1, Ugdh, Man1b1), protein biosynthesis (e.g., Sgk1, Alad, Fads3, Eif2c2, -3, Mat2a), and some circadian genes (Per1, -3), whereas others, such as Homer1a, remained unchanged. Moreover, several microRNAs were affected both by sleep deprivation and ADX. Conclusions: Our findings indicate that corticosterone contributes to the sleep-deprivation-induced changes in brain transcriptome that have been attributed to wakefulness per se. The study identified 78 transcripts that respond to sleep loss independent of corticosterone and time of day, among which genes involved in neuroprotection prominently feature, pointing to a molecular pathway directly relevant for sleep function.

Ideas, Possibilities and Limitations of Sustainable Economic Policy – the Example of Ecological Economics

A mesura que el suport del creixement econòmic constitueix un objectiu fonamental de la formulació de polítiques econòmiques, cal assenyalar que aquest tipus de creixement està limitat naturalment per un planeta finit. Aquest article argumenta que, des del punt de vista de la justícia intergeneracional, la realització d'un concepte de desmaterialització i, com a efecte, d'una economia que no creix (en el sentit de dissociació absoluta del creixement econòmic i consum d'energia i materials) es pot justificar. Per tant, el creixement pot ser també entesa com la millora de la qualitat de vida sobretot en comptes d'ampliar quantitats escarpats de sortida. Per tant, una dràstica reducció del cabal de material es necessita, sobretot en els països d'alts ingressos. Després de presentar alguns crítica de les propostes, en el focus d'aquest article es dibuixen en els arguments de per què la política econòmica en el futur han de ser etiquetats com "ecològic" i, a continuació, les opcions de posar en acció les idees del teòric presentat marc en tasques manejables polítiques seran discutides. En aquest cas, s'argumentarà que l'enfocament clàssic de internalització d'efectes externs sovint seguides de decisions de política econòmica ortodoxa no és completament capaç de reflectir canvis ecològics en les estructures de preus dels mercats. Per tant, formal (industrial i l'establiment de la política de consum) i institucions informals (llars) representen punts clau de la política econòmica sostenible, assenyalant l'individu com així com la responsabilitat col · lectiva per omplir aquest buit substancial.

The Strategic value of European renewable energy promotion policy

Encara falta per fer possible una transformació estratègica d'Europa del sistema d'energia, però el que és de la mateixa importància com a objectius a llarg termini de la FER i Reduccions de GEH són vinculants i forts objectius d'eficiència energètica, no només per 2020, però també per al 2030, 2040 i 2050, com aquesta força ajudaria a fixar l'augment de les energies renovables en el total d'energia consum i per reduir el total Emissions de GEH d'Europa en general, i les del sector de l'energia en particular, encara sent un dels majors emissors de gasos d'efecte hivernacle de tots els sectors. La refosa Directiva, prevista per 2011/12 ha de ser un bones finestres d'oportunitat per finalment establir objectius vinculants d'eficiència energètica, l'únic pilar que encara falta en la força energia interdependents i estratègia sobre el clima de la UE, basat en la reducció de gasos d'efecte hivernacle i i l'eficiència energètica.

Developmental effects of basic fibroblast growth factor and platelet-derived growth factor on glial cells in a three-dimensional cell culture system.

In order to study peptide growth factor action in a three-dimensional cellular environment, aggregating cell cultures prepared from 15-day fetal rat telencephalon were grown in a chemically defined medium and treated during an early developmental stage with either bovine fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF homodimers AA and BB). A single dose (5-50 ng/ml) of either growth factor given to the cultures on day 3 greatly enhanced the developmental increase of the two glia-specific enzyme activities, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glutamine synthetase (GS), whereas it had relatively little effect on total protein and DNA content. Distinct patterns of dose-dependency were found for CNP and GS stimulation. At low concentrations of bFGF (0.5-5 ng/ml) and at all PDGF concentrations applied, the oligodendroglial marker enzyme CNP was the most affected. A relatively small but significant mitogenic effect was observed after treatment with PDGF, particularly at higher concentrations or after repetitive stimulation. The two PDGF homodimers AA and BB were similar in their biological effects and potency. The present results show that under histotypic conditions both growth factors, bFGF and PDGF, promote the maturation rather than the proliferation of immature oligodendrocytes and astrocytes.

Characterization and simulation of a CdTe detector for use in PET

The Voxel Imaging PET (VIP) Path nder project got the 4 year European Research Council FP7 grant in 2010 to prove the feasibility of using CdTe detectors in a novel conceptual design of PET scanner. The work presented in this thesis is a part of the VIP project and consists of, on the one hand, the characterization of a CdTe detector in terms of energy resolution and coincidence time resolution and, on the other hand, the simulation of the setup with the single detector in order to extend the results to the full PET scanner. An energy resolution of 0.98% at 511 keV with a bias voltage of 1000 V/mm has been measured at low temperature T=-8 ºC. The coincidence time distribution of two twin detectors has been found to be as low as 6 ns FWHM for events with energies above 500 keV under the same temperature and bias conditions. The measured energy and time resolution values are compatible with similar ndings available in the literature and prove the excellent potential of CdTe for PET applications. This results have been presented in form of a poster contribution at the IEEE NSS/MIC & RTSD 2011 conference in October 2011 in Valencia and at the iWoRID 2012 conference in July 2012 in Coimbra, Portugal. They have been also submitted for publication to "Journal of Instrumentation (JINST)" in September 2012.

Variational calculation of static and dynamic vibrational nonlinear optical properties

The vibrational configuration interaction method used to obtain static vibrational (hyper)polarizabilities is extended to dynamic nonlinear optical properties in the infinite optical frequency approximation. Illustrative calculations are carried out on H2 O and N H3. The former molecule is weakly anharmonic while the latter contains a strongly anharmonic umbrella mode. The effect on vibrational (hyper)polarizabilities due to various truncations of the potential energy and property surfaces involved in the calculation are examined

The hardness profile as a tool to detect spurious stationary points in the potential energy surface

The energy and hardness profile for a series of inter and intramolecular conformational changes at several levels of calculation were computed. The hardness profiles were found to be calculated as the difference between the vertical ionization potential and electron affinity. The hardness profile shows the correct number of stationary points independently of the basis set and methodology used. It was found that the hardness profiles can be used to check the reliability of the energy profiles for those chemical system

Psychological distress in health sciences college students and its relationship with academic engagement

Objective: To determine the prevalence of psychological distress and its relationship with academic engagement (absorption, dedication and vigor), sex and degree among students from four public universities. Method: A non-experimental,comparative correlational, quantitative investigation without intervention. Study population: 1840 nursing and physical therapy students. The data collection tool used was a questionnaire. Results: A 32.2% prevalence of psychological distress was found in the subjects; a correlation between vigor and psychological distress was found for all of the subjects and also for women. High absorption and dedication scores and low psychological distress scores predicted higher vigor scores. Conclusion: The risk of psychological distress is high, especially for women. Women seem to have a higher level of psychological distress than men. Vigor, energy and mental resilience positively influence psychological distress and can be a vehicle for better results during the learning and studying process.