Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor xenografts: correlation with sensitizer uptake, tumor doubling time and tumor histology.

The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors

Moderate to vigorous physical activity and sedentary time and cardiometabolic risk factors in children and adolescents.

CONTEXT: Sparse data exist on the combined associations between physical activity and sedentary time with cardiometabolic risk factors in healthy children. OBJECTIVE: To examine the independent and combined associations between objectively measured time in moderate- to vigorous-intensity physical activity (MVPA) and sedentary time with cardiometabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS: Pooled data from 14 studies between 1998 and 2009 comprising 20 871 children (aged 4-18 years) from the International Children's Accelerometry Database. Time spent in MVPA and sedentary time were measured using accelerometry after reanalyzing raw data. The independent associations between time in MVPA and sedentary time, with outcomes, were examined using meta-analysis. Participants were stratified by tertiles of MVPA and sedentary time. MAIN OUTCOME MEASURES: Waist circumference, systolic blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and insulin. RESULTS: Times (mean [SD] min/d) accumulated by children in MVPA and being sedentary were 30 (21) and 354 (96), respectively. Time in MVPA was significantly associated with all cardiometabolic outcomes independent of sex, age, monitor wear time, time spent sedentary, and waist circumference (when not the outcome). Sedentary time was not associated with any outcome independent of time in MVPA. In the combined analyses, higher levels of MVPA were associated with better cardiometabolic risk factors across tertiles of sedentary time. The differences in outcomes between higher and lower MVPA were greater with lower sedentary time. Mean differences in waist circumference between the bottom and top tertiles of MVPA were 5.6 cm (95% CI, 4.8-6.4 cm) for high sedentary time and 3.6 cm (95% CI, 2.8-4.3 cm) for low sedentary time. Mean differences in systolic blood pressure for high and low sedentary time were 0.7 mm Hg (95% CI, -0.07 to 1.6) and 2.5 mm Hg (95% CI, 1.7-3.3), and for high-density lipoprotein cholesterol, differences were -2.6 mg/dL (95% CI, -1.4 to -3.9) and -4.5 mg/dL (95% CI, -3.3 to -5.6), respectively. Geometric mean differences for insulin and triglycerides showed similar variation. Those in the top tertile of MVPA accumulated more than 35 minutes per day in this intensity level compared with fewer than 18 minutes per day for those in the bottom tertile. In prospective analyses (N = 6413 at 2.1 years' follow-up), MVPA and sedentary time were not associated with waist circumference at follow-up, but a higher waist circumference at baseline was associated with higher amounts of sedentary time at follow-up. CONCLUSION: Higher MVPA time by children and adolescents was associated with better cardiometabolic risk factors regardless of the amount of sedentary time.

Surface deterioration of dental materials after simulated toothbrushing in relation to brushing time and load.

OBJECTIVES: (1) To evaluate the changes in surface roughness and gloss after simulated toothbrushing of 9 composite materials and 2 ceramic materials in relation to brushing time and load in vitro; (2) to assess the relationship between surface gloss and surface roughness. METHODS: Eight flat specimens of composite materials (microfilled: Adoro, Filtek Supreme, Heliomolar; microhybrid: Four Seasons, Tetric EvoCeram; hybrid: Compoglass F, Targis, Tetric Ceram; macrohybrid: Grandio), two ceramic materials (IPS d.SIGN and IPS Empress polished) were fabricated according to the manufacturer's instructions and optimally polished with up to 4000 grit SiC. The specimens were subjected to a toothbrushing (TB) simulation device (Willytec) with rotating movements, toothpaste slurry and at three different loads (100g/250g/350g). At hourly intervals from 1h to 10h TB, mean surface roughness Ra was measured with an optical sensor and the surface gloss (Gl) with a glossmeter. Statistical analysis was performed for log-transformed Ra data applying two-way ANOVA to evaluate the interaction between load and material and load and brushing time. RESULTS: There was a significant interaction between material and load as well as between load and brushing time (p<0.0001). The microhybrid and hybrid materials demonstrated more surface deterioration with higher loads, whereas with the microfilled resins Heliomolar and Adoro it was vice versa. For ceramic materials, no or little deterioration was observed over time and independent of the load. The ceramic materials and 3 of the composite materials (roughness) showed no further deterioration after 5h of toothbrushing. Mean surface gloss was the parameter which discriminated best between the materials, followed by mean surface roughness Ra. There was a strong correlation between surface gloss and surface roughness for all the materials except the ceramics. The evaluation of the deterioration curves of individual specimens revealed a more or less synchronous course suspecting hinting specific external conditions and not showing the true variability in relation to the tested material. SIGNIFICANCE: The surface roughness and gloss of dental materials changes with brushing time and load and thus results in different material rankings. Apart from Grandio, the hybrid composite resins were more prone to surface changes than microfilled composites. The deterioration potential of a composite material can be quickly assessed by measuring surface gloss. For this purpose, a brushing time of 10h (=72,000 strokes) is needed. In further comparative studies, specimens of different materials should be tested in one series to estimate the true variability.

Retinal thickening in HLA-B27 associated acute anterior uveitis: evolution with time and association with severity of inflammatory activity.

Purpose: To describe the evolution of retinal thickness in eyes affected with acute anterior uveitis (AAU) in the course of follow-up and to assess its correlation with severity of inflammatory activity in the anterior chamber. Methods: Design: Prospective, cohort study Setting: Institutional study Patient population: 72 eyes (affected and fellow eyes) of 36 patients Observation procedure: Patients were followed daily until beginning of resolution of inflammatory activity and weekly thereafter. Optical coherence tomography and laser flare photometry were performed at each visit. Treatment consisted of topical corticosteroids Main outcome measures: Retinal thickness of affected eyes, difference in retinal thickness between affected and fellow eyes and their evolution in time, association between maximal retinal thickness and initial laser flare photometry. Results: Difference in retinal thickness between affected and fellow eyes became significant on average seven days from baseline and remained so through-out follow-up (p<0.001). There was a steep increase in retinal thickness of affected eyes followed by a progressive decrease after reaching a peak value. Maximal difference in retinal thickness between affected and fellow eyes was observed between 17 and 25 days from baseline and exhibited a strong, positive correlation with initial laser flare photometry values (p=0.015). Conclusions: Retinal thickness in eyes affected with AAU presents a steep increase over 3 to 4 weeks and then gradually decreases. Severity of inflammation at baseline predicts the amount of retinal thickening in affected eyes. A characteristic pattern of temporal response of retinal anatomy to inflammatory stimuli seems to arise.

Nymph developmental time and survivorship, adult longevity, reproduction and body weight of Dichelops melacanthus (Dallas) feeding on natural and artificial diets

The biology of nymphs and adults of the neotropical pentatomid, Dichelops melacanthus (Dallas), feeding on the natural foods, soybean, Glycine max (L.) Merrill immature pods, and corn, Zea mays L. immature seeds, and on an artificial dry diet, was studied in the laboratory. Nymph developmental time was shorter on the natural foods (ca. 21-22 days) than on the artificial diet (28 days), and most nymphs reached adulthood on the food plants (55% on soybean and 73% on corn) than on the artificial diet (40%). Fresh body weight at adult emergence was similar and higher for females raised as nymphs on the natural foods, compared to females from nymphs raised on the artificial diet; for males, weights were similar on all foods. Mean (female and male) survivorship up to day 20, decreased from 55% on soybean to 40% on corn, down to 0% on the artificial diet. Total longevity for females was higher on soybean, while for males was similar on all foods. About three times more females oviposited on soybean than on corn, but fecundity/female was similar on both foods. On the artificial diet, only one out of 30 females oviposited. Fresh body weight of adults increased significantly during the first week of adult life, and at the end of the 3rd week, weight gain was similar on all foods.

Acute neurorehabilitation: does a neurosensory and coordinated interdisciplinary programme reduce tracheostomy weaning time and weaning failure?

BACKGROUND/PURPOSE: A new coordinated interdisciplinary unit was created in the acute section of the department of clinical neurosciences, the Acute NeuroRehabilitation (NRA) unit. The objective was to evaluate the impact of the unit and its neurosensory programme on the management of tracheostomy patients in terms of reduction in the average time taken for weaning, weaning success rate and therapeutic efficiency. METHODS: This 49-month retrospective study compares 2 groups of tracheostomy patients before (n = 34) and after (n = 46) NRA intervention. The outcome measures evaluate the benefits of the NRA unit intervention (time to decannulation, weaning and complication rates) and the benefits of the coordination (time to registration in a rehabilitation centre and rate of non-compliance with standards of care). RESULTS: Weaning failure rate was reduced from 27.3% to 9.1%, no complications or recannulations were observed in the post-intervention group after weaning and time to decannulation following admission to our unit decreased from 19.13 to 12.75 days. The rate of non-compliance with patient standards of care was significantly reduced from 45% to 30% (Mann-Whitney p = 0.003). DISCUSSION/CONCLUSIONS: This interdisciplinary weaning programme helped to reduce weaning time and weaning failure, without increased complications, in the sample studied. Coordination improved the efficiency of the interdisciplinary team in the multiplicity and complexity of the different treatments.

Changes in leisure time and occupational physical activity over 8 years: The Cornellà health Interview Survey Follow-Up Study

Aim: To describe changes in leisure time and occupational physical activity status in an urban Mediterranean population-based cohort, and to evaluate sociodemographic, health-related and lifestyle correlates of such changes. Methods: Data for this study come from the Cornellè Health Interview Survey Follow-Up Study, a prospective cohort study of a representative sample (n¿=¿2500) of the population. Participants in the analysis reported here include 1246 subjects (567 men and 679 women) who had complete data on physical activity at the 1994 baseline survey and at the 2002 follow-up. We fitted Breslow-Cox regression models to assess the association between correlates of interest and changes in physical activity. Results: Regarding leisure time physical activity, 61.6% of cohort members with ¿sedentary¿ habits in 1994 changed their status to ¿light/moderate¿ physical activity in 2002, and 70% who had ¿light/moderate¿ habits in 1994 did not change their activity level. Regarding occupational physical activity, 74.4% of cohort members who were ¿active¿ did not change their level of activity, and 64.3% of participants with ¿sedentary¿ habits in 1994 changed to ¿active¿ occupational physical activity. No clear correlates of change in physical activity were identified in multivariate analyses. Conclusion: While changes in physical activity are evident in this population-based cohort, no clear determinants of such changes were recognised. Further longitudinal studies including other potential individual and contextual determinants are needed to better understand determinants of changes in physical activity at the population level.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort

Abstract Background and aims. Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. Methods. Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. Results. Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. Conclusion. Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Linking Real Time and Location in Scheduling Demand-Responsive Transit, September 1996

The role of rural demand-responsive transit is changing, and with that change is coming an increasing need for technology. As long as rural transit was limited to a type of social service transportation for a specific set of clients who primarily traveled in groups to common meal sites, work centers for the disabled, or clinics in larger communities, a preset calendar augmented by notes on a yellow legal pad was sufficient to develop schedules. Any individual trips were arranged at least 24 to 48 hours ahead of time and were carefully scheduled the night before in half-hour or twenty-minute windows by a dispatcher who knew every lane in the service area. Since it took hours to build the schedule, any last-minute changes could wreak havoc with the plans and raise the stress level in the dispatch office. Nevertheless, given these parameters, a manual scheduling system worked for a small demand-responsive operation.

The nonlinear relaxation time and quasideterministic-theory approaches to characterize the decay of unestable states

We present the relationship between nonlinear-relaxation-time (NLRT) and quasideterministic approaches to characterize the decay of an unstable state. The universal character of the NLRT is established. The theoretical results are applied to study the dynamical relaxation of the Landau model in one and n variables and also a laser model.

Nonlinear relaxation time and the detection of weak signals

Laser systems can be used to detect very weak optical signals. The physical mechanism is the dynamical process of the relaxation of a laser from an unstable state to a steady stable state. We present an analysis of this process based on the study of the nonlinear relaxation time. Our analytical results are compared with numerical integration of the stochastic differential equations that model this process.

Distinct levels in Pom1 gradients limit Cdr2 activity and localization to time and position division.

Where and when cells divide are fundamental questions. In rod-shaped fission yeast cells, the DYRK-family kinase Pom1 is organized in concentration gradients from cell poles and controls cell division timing and positioning. Pom1 gradients restrict to mid-cell the SAD-like kinase Cdr2, which recruits Mid1/Anillin for medial division. Pom1 also delays mitotic commitment through Cdr2, which inhibits Wee1. Here, we describe quantitatively the distributions of cortical Pom1 and Cdr2. These reveal low profile overlap contrasting with previous whole-cell measurements and Cdr2 levels increase with cell elongation, raising the possibility that Pom1 regulates mitotic commitment by controlling Cdr2 medial levels. However, we show that distinct thresholds of Pom1 activity define the timing and positioning of division. Three conditions-a separation-of-function Pom1 allele, partial downregulation of Pom1 activity, and haploinsufficiency in diploid cells-yield cells that divide early, similar to pom1 deletion, but medially, like wild-type cells. In these cells, Cdr2 is localized correctly at mid-cell. Further, Cdr2 overexpression promotes precocious mitosis only in absence of Pom1. Thus, Pom1 inhibits Cdr2 for mitotic commitment independently of regulating its localization or cortical levels. Indeed, we show Pom1 restricts Cdr2 activity through phosphorylation of a C-terminal self-inhibitory tail. In summary, our results demonstrate that distinct levels in Pom1 gradients delineate a medial Cdr2 domain, for cell division placement, and control its activity, for mitotic commitment.

Basil conservation affected by cropping season, harvest time and storage period

Fresh basil (Ocimum basilicum L.) is used in food, phytotherapic industry, and in traditional therapeutic, due to its essential oil content and composition. Nevertheless basil can not be kept for long periods after harvest and its quality can be reduced. This work aimed to assess the influence of the season and harvest time in the postharvest conservation of basil stored for different periods. Basil was harvested at 8 am and 4 pm both in August/1999 and January/2000. Cuttings were conditioned in PVC packages and stored for 3, 6, and 9 days. During storage, chlorophyll content, essential oil content and composition were determined as well as microbiological analyses were carried out. Harvest season and the days of storage influenced the final content of essential oil. There was a linear decrease in the content of essential oil, in the chlorophyll content and in the number of mold and yeast colonies during storage. There was no effect of cropping season or harvest hour on essential oil composition, but the eugenol and linalool content increased during storage. Coliforms were under 0.3 MPN g-1 and the number of Staphylococcus aureus was under 1.0x10² UFC g-1.

Nonpoint source pollution, space, time and asymetric information - a deposit refund approach

The incorporation of space allows the establishment of a more precise relationship between a contaminating input, a contaminating byproduct and emissions that reach the final receptor. However, the presence of asymmetric information impedes the implementation of the first-best policy. As a solution to this problem a site specific deposit refund system for the contaminating input and the contaminating byproduct are proposed. Moreover, the utilization of a successive optimization technique first over space and second over time enables definition of the optimal intertemporal site specific deposit refund system

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort.

Abstract Background and aims. Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. Methods. Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. Results. Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. Conclusion. Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.