Effects of potentised substances on growth kinetics of Saccharomyces cerevisiae and Schizosaccharomyces pombe

BACKGROUND: Homeopathic potencies are used as specific remedies in complementary medicine. Since the mode of action is unknown, the presumed specificity is discussed controversially. OBJECTIVE: This study investigated the effects of potentised substances on two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe, in a stable and reliable test system with systematic negative controls. MATERIALS AND METHODS: Yeast cells were cultivated in either potentised substances or water controls in microplates and their growth kinetics were measured photometrically. Water control runs were performed repeatedly to investigate the stability of the experimental set-up (systematic negative controls). RESULTS: 4 out of 14 screened substances seem to have affected the growth curve parameters slope or yield. Out of these substances, azoxystrobin and phosphorus were chosen for 8 further replication experiments, which partly confirmed the results of the screening. On the average of all experiments, azoxystrobin affected the slope of the growth curve of Saccharomyces cerevisiae (p < 0.05), and phosphorus affected the slope of the growth curve of Schizosaccharomyces pombe (p < 0.05). No effects were seen in the water control runs. In addition, significant interactions between treatment with potentised substances and experiment number were observed in all experiments with potentised substances (p < 0.01), but not in the water control runs. CONCLUSIONS: Both yeast species reacted to certain potentised substances by changing their growth kinetics. However, the interactions found point to additional factors of still unknown nature, that modulate the effects of potentised substances. This stable test system with yeasts may be suitable for further studies regarding the efficacy of homeopathic potencies.

Prediction of first coronary events with the Framingham score: a systematic review

BACKGROUND: Uncertainty exists about the performance of the Framingham risk score when applied in different populations. OBJECTIVE: We assessed calibration of the Framingham risk score (ie, relationship between predicted and observed coronary event rates) in US and non-US populations free of cardiovascular disease. METHODS: We reviewed studies that evaluated the performance of the Framingham risk score to predict first coronary events in a validation cohort, as identified by Medline, EMBASE, BIOSIS, and Cochrane library searches (through August 2005). Two reviewers independently assessed 1496 studies for eligibility, extracted data, and performed quality assessment using predefined forms. RESULTS: We included 25 validation cohorts of different population groups (n = 128,000) in our main analysis. Calibration varied over a wide range from under- to overprediction of absolute risk by factors of 0.57 to 2.7. Risk prediction for 7 cohorts (n = 18658) from the United States, Australia, and New Zealand was well calibrated (corresponding figures: 0.87-1.08; for the 5 biggest cohorts). The estimated population risks for first coronary events were strongly associated (goodness of fit: R2 = 0.84) and in good agreement with observed risks (coefficient for predicted risk: beta = 0.84; 95% CI 0.41-1.26). In 18 European cohorts (n = 109499), the corresponding figures indicated close association (R2 = 0.72) but substantial overprediction (beta = 0.58, 95% CI 0.39-0.77). The risk score was well calibrated on the intercept for both population clusters. CONCLUSION: The Framingham score is well calibrated to predict first coronary events in populations from the United States, Australia, and New Zealand. Overestimation of absolute risk in European cohorts requires recalibration procedures.

Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

BACKGROUND: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. PATIENTS AND METHODS: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. RESULTS: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. CONCLUSION: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.

Primary care physician supply and other key determinants of health care utilisation: The case of Switzerland

Background The Swiss government decided to freeze new accreditations for physicians in private practice in Switzerland based on the assumption that demand-induced health care spending may be cut by limiting care offers. This legislation initiated an ongoing controversial public debate in Switzerland. The aim of this study is therefore the determination of socio-demographic and health system-related factors of per capita consultation rates with primary care physicians in the multicultural population of Switzerland. Methods The data were derived from the complete claims data of Swiss health insurers for 2004 and included 21.4 million consultations provided by 6564 Swiss primary care physicians on a fee-for-service basis. Socio-demographic data were obtained from the Swiss Federal Statistical Office. Utilisation-based health service areas were created and were used as observational units for statistical procedures. Multivariate and hierarchical models were applied to analyze the data. Results Models within the study allowed the definition of 1018 primary care service areas with a median population of 3754 and an average per capita consultation rate of 2.95 per year. Statistical models yielded significant effects for various geographical, socio-demographic and cultural factors. The regional density of physicians in independent practice was also significantly associated with annual consultation rates and indicated an associated increase 0.10 for each additional primary care physician in a population of 10,000 inhabitants. Considerable differences across Swiss language regions were observed with reference to the supply of ambulatory health resources provided either by primary care physicians, specialists, or hospital-based ambulatory care. Conclusion The study documents a large small-area variation in utilisation and provision of health care resources in Switzerland. Effects of physician density appeared to be strongly related to Swiss language regions and may be rooted in the different cultural backgrounds of the served populations.

The spatial distribution of Copernicia alba (Morong) in the district of Bahia Negra, Paraguay

The Humid Chaco of Northeast Paraguay harbors monoculture palm savannas in which Copernicia alba is the only dominant overstory species. The study’s objective was to provide the complete spatial distribution of a simple ecosystem lacking confounding factors of overstory competition and changes in slope. Palms within six, 50 x 50m plots were marked by their GPS location and measured for dbh and total stem height. The spatial distribution was individually analyzed for each plot at the local scale up to 12 m using Ripley’s K test. For the total population including juvenile and adult plants, the sample plots contained both random and clustered distribution patterns. In each of the six plots, the juvenile populations exhibited more clustered patterns than the adult population of each plot.

Kinetic characterization for pretreatment of timber varieties and switchgrass using diluted acid hydrolysis

In recent years, growing attention has been devoted to the use of lignocellulosic biomass as a feedstock to produce renewable carbohydrates as a source of energy products, including liquid alternatives to fossil fuels. The benefits of developing woody biomass to ethanol technology are to increase the long-term national energy security, reduce fossil energy consumption, lower greenhouse gas emissions, use renewable rather than depletable resources, and create local jobs. Currently, research is driven by the need to reduce the cost of biomass-ethanol production. One of the preferred methods is to thermochemically pretreat the biomass material and subsequently, enzymatically hydrolyze the pretreated material to fermentable sugars that can then be converted to ethanol using specialized microorganisms. The goals of pretreatment are to remove the hemicellulose fraction from other biomass components, reduce bioconversion time, enhance enzymatic conversion of the cellulose fraction, and, hopefully, obtain a higher ethanol yield. The primary goal of this research is to obtain kinetic detailed data for dilute acid hydrolysis for several timber species from the Upper Peninsula of Michigan and switchgrass. These results will be used to identify optimum reaction conditions to maximize production of fermentable sugars and minimize production of non-fermentable byproducts. The structural carbohydrate analysis of the biomass species used in this project was performed using the procedure proposed by National Renewable Energy Laboratory (NREL). Subsequently, dilute acid-catalyzed hydrolysis of biomass, including aspen, basswood, balsam, red maple, and switchgrass, was studied at various temperatures, acid concentrations, and particle sizes in a 1-L well-mixed batch reactor (Parr Instruments, ii Model 4571). 25 g of biomass and 500 mL of diluted acid solution were added into a 1-L glass liner, and then put into the reactor. During the experiment, 5 mL samples were taken starting at 100°C at 3 min intervals until reaching the targeted temperature (160, 175, or 190°C), followed by 4 samples after achieving the desired temperature. The collected samples were then cooled in an ice bath immediately to stop the reaction. The cooled samples were filtered using 0.2 μm MILLIPORE membrane filter to remove suspended solids. The filtered samples were then analyzed using High Performance Liquid Chromatography (HPLC) with a Bio-Rad Aminex HPX-87P column, and refractive index detection to measure monomeric and polymeric sugars plus degradation byproducts. A first order reaction model was assumed and the kinetic parameters such as activation energy and pre-exponential factor from Arrhenius equation were obtained from a match between the model and experimental data. The reaction temperature increases linearly after 40 minutes during experiments. Xylose and other sugars were formed from hemicellulose hydrolysis over this heat up period until a maximum concentration was reached at the time near when the targeted temperature was reached. However, negligible amount of xylose byproducts and small concentrations of other soluble sugars, such as mannose, arabinose, and galactose were detected during this initial heat up period. Very little cellulose hydrolysis yielding glucose was observed during the initial heat up period. On the other hand, later in the reaction during the constant temperature period xylose was degraded to furfural. Glucose production from cellulose was increased during this constant temperature period at later time points in the reaction. The kinetic coefficient governing the generation of xylose from hemicellulose and the generation of furfural from xylose presented a coherent dependence on both temperature and acid concentration. However, no effect was observed in the particle size. There were three types of biomass used in this project; hardwood (aspen, basswood, and red maple), softwood (balsam), and a herbaceous crop (switchgrass). The activation energies and the pre-exponential factors of the timber species and switchgrass were in a range of 49 - 180 kJ/mol and from 7.5x104 - 2.6x1020 min-1, respectively, for the xylose formation model. In addition, for xylose degradation, the activation energies and the preexponential factors ranged from 130 - 170 kJ/mol and from 6.8x1013 - 3.7x1017 min-1, respectively. The results compare favorably with the literature values given by Ranganathan et al, 1985. Overall, up to 92 % of the xylose was able to generate from the dilute acid hydrolysis in this project.

Effects of fixed night shift work on 24 hour blood pressure regulation, state anxiety levels and total sleep time

Nearly 22 million Americans operate as shift workers, and shift work has been linked to the development of cardiovascular disease (CVD). This study is aimed at identifying pivotal risk factors of CVD by assessing 24 hour ambulatory blood pressure, state anxiety levels and sleep patterns in 12 hour fixed shift workers. We hypothesized that night shift work would negatively affect blood pressure regulation, anxiety levels and sleep patterns. A total of 28 subjects (ages 22-60) were divided into two groups: 12 hour fixed night shift workers (n=15) and 12 hour fixed day shift workers (n=13). 24 hour ambulatory blood pressure measurements (Space Labs 90207) were taken twice: once during a regular work day and once on a non-work day. State anxiety levels were assessed on both test days using the Speilberger’s State Trait Anxiety Inventory. Total sleep time (TST) was determined using self recorded sleep diary. Night shift workers demonstrated increases in 24 hour systolic (122 ± 2 to 126 ± 2 mmHg, P=0.012); diastolic (75 ± 1 to 79 ± 2 mmHg, P=0.001); and mean arterial pressures (90 ± 2 to 94 ± 2mmHg, P<0.001) during work days compared to off days. In contrast, 24 hour blood pressures were similar during work and off days in day shift workers. Night shift workers reported less TST on work days versus off days (345 ± 16 vs. 552 ± 30 min; P<0.001), whereas day shift workers reported similar TST during work and off days (475 ± 16 minutes to 437 ± 20 minutes; P=0.231). State anxiety scores did not differ between the groups or testing days (time*group interaction P=0.248), suggesting increased 24 hour blood pressure during night shift work is related to decreased TST, not short term anxiety. Our findings suggest that fixed night shift work causes disruption of the normal sleep-wake cycle negatively affecting acute blood pressure regulation, which may increase the long-term risk for CVD.

UNDERSTANDING PEOPLE'S ADOPTION OF INDIVIDUAL-USE RENEWABLE ENERGY TECHNOLOGY

This thesis attempts to understand why people adopt or reject individual-use renewable energy technologies (IURET). I used factors from Everett Rogers' Diffusion of Innovation Theory to understand how people's perceptions towards the characteristics of a given IURET (such as price, compatibility, complexity, etc.), the characteristics of the individual adopter (such as innovativeness and environmental awareness), and the communication network (inter-personal communications and mass media) can influence adoption. An online questionnaire was sent to 101randomly selected Michigan households (using random digit dialing) to ask people whether or not they had adopted at least one IURET and to assess the above-mentioned factors from Rogers' theory. Data analysis was then conducted in SPSS using Chi-squared and binary logistic regression to determine the relationship between adoption behaviors (the dependent variable) and the factors from Rogers' theory (the independent variables) while controlling for education. The results show that Rogers' factors of price and observability and the control variable of education were all significant in explaining adoption but the other factors of Rogers' theory were not. For example, if individuals perceive the price of IURET to be reasonable or if they observe their neighbors using these technologies, then they are more likely to adopt. These results indicate that, if we want to promote greater adoption of IURET, we should focus our efforts on making the price of IURET more affordable through incentives and other mechanisms. Adopters should also be given some form of reward if they provide free demonstrations of their IURET in use to their neighbors to take advantage of the observability effects.

Hospital use of young children in Switzerland: a nation-wide study based on a complete survey over 4 years

Background Young children are known to be the most frequent hospital users compared to older children and young adults. Therefore, they are an important population from economic and policy perspectives of health care delivery. In Switzerland complete hospitalization discharge records for children [<5 years] of four consecutive years [2002–2005] were evaluated in order to analyze variation in patterns of hospital use. Methods Stationary and outpatient hospitalization rates on aggregated ZIP code level were calculated based on census data provided by the Swiss federal statistical office (BfS). Thirty-seven hospital service areas for children [HSAP] were created with the method of "small area analysis", reflecting user-based health markets. Descriptive statistics and general linear models were applied to analyze the data. Results The mean stationary hospitalization rate over four years was 66.1 discharges per 1000 children. Hospitalizations for respiratory problem are most dominant in young children (25.9%) and highest hospitalization rates are associated with geographical factors of urban areas and specific language regions. Statistical models yielded significant effect estimates for these factors and a significant association between ambulatory/outpatient and stationary hospitalization rates. Conclusion The utilization-based approach, using HSAP as spatial representation of user-based health markets, is a valid instrument and allows assessing the supply and demand of children's health care services. The study provides for the first time estimates for several factors associated with the large variation in the utilization and provision of paediatric health care resources in Switzerland.

IMPACT OF 2000-2050 CLIMATE CHANGE ON GLOBAL ATMOSPHERIC TRANSPORT AND DEPOSITION OF MERCURY

Since it is very toxic and accumulates in organisms, particularly in fish, mercury is a very important pollutant and one of the most studies. And this concern over the toxicity and human health risks of mercury has prompted efforts to regulate anthropogenic emissions. As mercury pollution problem is getting increasingly serious, we are curious about how serious this problem will be in the future. What is more, how the climate change in the future will affect the mercury concentration in the atmosphere. So we investigate the impact of climate change on mercury concentration in the atmosphere. We focus on the comparison between the mercury data for year 2000 and for year 2050. The GEOS-Chem model shows that the mercury concentrations for all tracers (1 to 3), elemental mercury (Hg(0)), divalent mercury (Hg(II)) and primary particulate mercury (Hg(P)) have differences between 2000 and 2050 in most regions over the world. From the model results, we can see the climate change from 2000 to 2050 would decrease Hg(0) surface concentration in most of the world. The driving factors of Hg(0) surface concentration changes are natural emissions(ocean and vegetation) and the transformation reactions between Hg(0) and Hg(II). The climate change from 2000 to 2050 would increase Hg(II) surface concentration in most of mid-latitude continental parts of the world while decreasing Hg(II) surface concentration in most of high-latitude part of the world. The driving factors of Hg(II) surface concentration changes is deposition amount change (majorly wet deposition) from 2000 to 2050 and the transformation reactions between Hg(0) and Hg(II). Climate change would increase Hg(P) concentration in most of mid-latitude area of the world and meanwhile decrease Hg(P) concentration in most of high-latitude regions of the world. For the Hg(P) concentration changes, the major driving factor is the deposition amount change (mainly wet deposition) from 2000 to 2050.

Chronic rejection in lung allografts: immunohistological analysis of fibrogenesis

In ongoing chronic rejection after lung transplantation, alveolar interstitial fibrosis develops. However, little is known about the mechanisms involved. In order to investigate these mechanisms, expression of extracellular matrix molecules (ECM) (undulin, decorin, tenascin, laminin, and fibronectin) and cytokines [transforming growth factor (TGF)-beta 1, TGF-beta 3, platelet-derived growth factor (PDGF), and PDGF receptor] were semiquantitatively evaluated in chronically rejected lung allografts, using standard immunohistochemical techniques. Additionally, the presence of macrophages was analysed. The present study demonstrates an increased infiltration of macrophages with a concomitant upregulation of cytokines (TGF-beta 1, TGF-beta 3, and PDGF) and an increased deposition of ECM in chronic lung rejection. These cytokines have an important role in the stimulation of fibroblasts which are a major source of ECM. Upregulated expression of ECM in the alveolar interstitial space leads to alveolar malfunction by thickening of the wall and, thus, is one of the causative factors of respiratory dysfunction in chronic lung graft rejection.

Prognosis of HIV-associated non-Hodgkin lymphoma in patients starting combination antiretroviral therapy

OBJECTIVE: We examined survival and prognostic factors of patients who developed HIV-associated non-Hodgkin lymphoma (NHL) in the era of combination antiretroviral therapy (cART). DESIGN AND SETTING: Multicohort collaboration of 33 European cohorts. METHODS: We included all cART-naive patients enrolled in cohorts participating in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who were aged 16 years or older, started cART at some point after 1 January 1998 and developed NHL after 1 January 1998. Patients had to have a CD4 cell count after 1 January 1998 and one at diagnosis of the NHL. Survival and prognostic factors were estimated using Weibull models, with random effects accounting for heterogeneity between cohorts. RESULTS: Of 67 659 patients who were followed up during 304 940 person-years, 1176 patients were diagnosed with NHL. Eight hundred and forty-seven patients (72%) from 22 cohorts met inclusion criteria. Survival at 1 year was 66% [95% confidence interval (CI) 63-70%] for systemic NHL (n = 763) and 54% (95% CI: 43-65%) for primary brain lymphoma (n = 84). Risk factors for death included low nadir CD4 cell counts and a history of injection drug use. Patients developing NHL on cART had an increased risk of death compared with patients who were cART naive at diagnosis. CONCLUSION: In the era of cART two-thirds of patients diagnosed with HIV-related systemic NHL survive for longer than 1 year after diagnosis. Survival is poorer in patients diagnosed with primary brain lymphoma. More advanced immunodeficiency is the dominant prognostic factor for mortality in patients with HIV-related NHL.

Factors related to treatment intensity in Swiss primary care

BACKGROUND: Questions about the existence of supplier-induced demand emerge repeatedly in discussions about governing Swiss health care. This study therefore aimed to evaluate the interrelationship between structural factors of supply and the volume of services that are provided by primary care physicians in Switzerland. METHODS: The study was designed as a cross-sectional investigation, based on the complete claims data from all Swiss health care insurers for the year 2004, which covered information from 6087 primary care physicians and 4.7 million patients. Utilization-based health service areas were constructed and used as spatial units to analyze effects of density of supply. Hierarchical linear models were applied to analyze the data. RESULTS: The data showed that, within a service area, a higher density of primary care physicians was associated with higher mortality rates and specialist density but not with treatment intensity in primary care. Higher specialist density was weakly associated with higher mortality rates and with higher treatment intensity density of primary care physicians. Annual physician-level data indicate a disproportionate increase of supplied services irrespective of the size of the number of patients treated during the same year and, even in high volume practices, no rationing but a paradoxical inducement of consultations occurred. The results provide empirical evidence that higher densities of primary care physicians, specialists and the availability of out-patient hospital clinics in a given area are associated with higher volume of supplied services per patient in primary care practices. Analyses stratified by language regions showed differences that emphasize the effect of the cantonal based (fragmented) governance of Swiss health care. CONCLUSION: The study shows high volumes in Swiss primary care and provides evidence that the volume of supply is not driven by medical needs alone. Effects related to the competition for patients between primary care physicians, specialists and out-patient hospital clinics and an association with the system of reimbursing services on a fee-for-service basis can not be excluded.

Association of vital exhaustion and depressive symptoms with changes in fibrin D-dimer to acute psychosocial stress

OBJECTIVE: Vital exhaustion and depression are psychosocial risk factors of coronary artery disease. A hypercoagulable state in response to acute psychosocial stress contributes to atherothrombotic events. We aimed to investigate the hypothesis that vital exhaustion and depression correlate with stress-induced changes in the hypercoagulability marker D-dimer. METHODS: Thirty-eight healthy and nonsmoking school teachers (mean age 50+/-8 years, 55% women) completed the nine-item Maastricht Vital Exhaustion Questionnaire and the seven-item depression subscale of the Hospital Anxiety and Depression Scale. Within 1 week, subjects twice underwent the Trier Social Stress Test (i.e., preparation phase, mock job interview, and mental arithmetic that totaled 13 min). Plasma D-dimer levels were determined at five time points during the protocol. RESULTS: Vital exhaustion (P=.022; eta(2)=.080) and depressive symptoms (P=.011; eta(2)=.090) were associated with stress-induced changes in D-dimer levels over time controlling for sex and age. Elevated levels of vital exhaustion (r=-.46, P=.005) and of depression (r=-.51, P=.002) correlated with reduced D-dimer increase from pre-stress to immediately post-stress. Also, elevated vital exhaustion (r=.34, P=.044) and depression (r=.41, P=.013) were associated with increase (i.e., attenuated recovery) of D-dimer levels between 20 and 45 min post-stress. Controlling for stress hormone and blood pressure reactivity did not substantially alter these results. CONCLUSION: The findings suggest an attenuated immediate D-dimer stress response and delayed recovery of D-dimer levels post-stress with elevated vital exhaustion and depressive symptoms. In particular, the prolonged hypercoagulability after stress cessation might contribute to the atherothrombotic risk previously observed with vital exhaustion and depression, even at subclinical levels.

Early- and delayed antipsychotic response and prediction of outcome in 528 severely impaired patients with schizophrenia treated with amisulpride

'Early-onset' studies have shown that symptomatic response often occurs early and that early symptomatic response is predictive for later outcome. Limiting factors of these studies include the restriction on symptomatic outcome, the inclusion of mostly moderately ill patients, and the use of various antipsychotics.