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Key Points: Question: What are the characteristics of patients in California with silicosis from occupational exposure to dust from engineered stone (quartz), a popular material that is high in silica content and that is used to fabricate countertops? Findings: In this case series of 52 patients, the median age was 45 years at diagnosis, and nearly all were Latino immigrant men. Diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died. Meaning: In California, silicosis associated with occupational exposure to dust from engineered stone primarily occurred among young Latino immigrant men; many patients presented with severe disease, and some cases were fatal.

ImportanceSilicosis associated with inhalation of respirable crystalline silica among engineered stone countertop fabrication workers is an emerging health concern.ObjectiveTo describe clinical, socioeconomic, and occupational characteristics of patients diagnosed with silicosis associated with engineered stone in California.Design, setting, and participantsThis case series included reported cases of silicosis associated with fabrication of engineered stone countertops, as identified by statewide surveillance by the California Department of Public Health (2019-2022). Data analysis was performed from October 2022 to March 2023.ExposuresPatient interviews and medical record abstractions were used to assess occupational exposure to respirable crystalline silica, including duration of work tenure and preventive measures undertaken.Main outcomes and measuresDemographics, clinical characteristics, health care utilization, and clinical outcomes were obtained, including vital status, hypoxia, and lung transplant.ResultsThis case series identified 52 male patients meeting inclusion criteria; median (IQR) age was 45 (40-49) years, and 51 were Latino immigrants. Ten (19%) were uninsured, and 20 (39%) had restricted-scope Medi-Cal; 25 (48%) presented initially to an emergency department. A delay in diagnosis occurred in 30 (58%) patients, most commonly due to alternative initial diagnoses of bacterial pneumonia (9 [30%]) or tuberculosis (8 [27%]). At diagnosis, 20 (38%) patients had advanced disease (progressive massive fibrosis) with severely or very severely reduced forced expiratory volume in 1 second in 8 (18%) and 5 (11%), respectively. Of the cases, 10 (19%) were fatal; median (IQR) age at death was 46 (38-51) years, and 6 patients (12%) were alive with chronic resting hypoxia. Eleven were referred for lung transplant: 3 underwent transplant with 1 fatality; 7 were declined transplant, with 6 fatalities; and 1 died prior to listing. Median (IQR) work tenure was 15 (10-20)

Ergo, an Open Access Journal of Philosophy: vol. 7, (dlps) 12405314.0007.012, http://hdl.handle.net/2027/spo.12405314.0007.012, This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Please contact mpub-help@umich.edu to use this work in a way not covered by the license.

Science, technology, engineering, and mathematics, often referred to as STEM, have been the cornerstone for American success through innovation and entrepreneurialism. Concerns for economic prosperity and national security, as well as a concern for creating a technological and scientifically literate society, have created tremendous support for STEM education at the federal, state, and local levels. Despite this trend, jobs in STEM fields continue to go unfilled and are disproportionately underrepresented by minoritized groups. Recently, STEM has been expanded to STEAM, (Science, Technology, Engineering, Arts, and Math), presumably to widen the appeal of STEM subjects by including an emphasis on the arts and creative expression (Herro & Quigley, 2019; Johnson, 2014). STEAM is a transdisciplinary approach that applies academic concepts to a consideration of real-world issues as a catalyst to teach academic concepts, communications skills, and critical thinking while building soft skills such as cooperation, adaptability, and creativity. A rising tide among educators and other stakeholders is building momentum for the changes in methods, materials, and instructional practices required for STEAM pedagogy to take root. Ultimately, this practice must be implemented at the micro-level, in classrooms with teachers and students. How can schools prepare educators to make this change? This study will investigate the effectiveness of a professional development intervention to support teachers as they develop lesson plans that integrate STEAM pedagogy and career readiness, focusing on the process skills required for success in a changing work environment. The study was conducted in a small suburban school district. A small group of K-12 teachers participated in a virtual professional learning experience that included interactions with professionals working in STEAM fields. Changes in understanding, attitudes, and feelings of efficacy were analyzed through a mixed-methods approa

Science, technology, engineering, and mathematics, often referred to as STEM, have been the cornerstone for American success through innovation and entrepreneurialism. Concerns for economic prosperity and national security, as well as a concern for creating a technological and scientifically literate society, have created tremendous support for STEM education at the federal, state, and local levels. Despite this trend, jobs in STEM fields continue to go unfilled and are disproportionately underrepresented by minoritized groups. Recently, STEM has been expanded to STEAM, (Science, Technology, Engineering, Arts, and Math), presumably to widen the appeal of STEM subjects by including an emphasis on the arts and creative expression (Herro & Quigley, 2019; Johnson, 2014). STEAM is a transdisciplinary approach that applies academic concepts to a consideration of real-world issues as a catalyst to teach academic concepts, communications skills, and critical thinking while building soft skills such as cooperation, adaptability, and creativity. A rising tide among educators and other stakeholders is building momentum for the changes in methods, materials, and instructional practices required for STEAM pedagogy to take root. Ultimately, this practice must be implemented at the micro-level, in classrooms with teachers and students. How can schools prepare educators to make this change? This study will investigate the effectiveness of a professional development intervention to support teachers as they develop lesson plans that integrate STEAM pedagogy and career readiness, focusing on the process skills required for success in a changing work environment. The study was conducted in a small suburban school district. A small group of K-12 teachers participated in a virtual professional learning experience that included interactions with professionals working in STEAM fields. Changes in understanding, attitudes, and feelings of efficacy were analyzed through a mixed-methods approa

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The Global Land and Marine Observations Database aims to produce a comprehensive land-based meteorological data archive and inventory. This requires the compilation of available information on data from land-based meteorological stations from all known available in situ meteorological data repositories/sources at multiple timescales (e.g. sub-daily, daily, and monthly). During this process the service team members have identified that many of the data sources contain stations with incorrect location coordinates. These stations cannot be included in the processing to be served via the Copernicus Climate Change Service until the issues are satisfactorily resolved. Many of these stations are in regions of the world where a sparsity of climate data currently exists, such as Southeast Asia and South America. As such, resolving these issues would provide important additional climate data, but this is a very labour-intensive task. Therefore, we have developed the Geo-locate project – that enrols the help of undergraduate geography students at Maynooth University, Ireland – to resolve some of the landbased station geolocation issues. To date, we have run two Geo-locate projects: the first in the 2017/2018 academic year and the second in the 2018/2019 academic year. Both iterations have been very successful with 1926 of the 2168 total candidate stations ostensibly resolved, which equates to an 88 % success rate. At the same time, students have gained critical skills that helped to meet the expected pedagogical outcomes of the second-year curriculum, while producing a lasting scientific legacy. We asked the class of 2018/2019 to reflect critically upon the outcomes, and we present the results herein; these results provide important feedback on what students felt that they gained from their participation and how we may improve the experience and learning outcomes in future. We will be continuing to run Geo-locate projects over the next few years. We encourage other organizatio

Soil is a complex material capable of storing and releasing large amounts of carbon, making it an integral part of the global carbon cycle. As soil is included in national inventory assessments where countries quantify their emissions, it is important that estimates of the soil carbon flux are as accurate as possible. Measuring the flux of carbon from every surface on the planet is unrealistic, therefore modelling emissions is the next best method of emissions assessment. Among modelling approaches, process-based modelling allows for the highest specificity of input data. Process-based models split soil carbon into pools with different decay rates influenced by environmental (biotic and abiotic) factors and management. The Estimation of Carbon in Organic Soils – Sequestration and Emissions (ECOSSE) model has previously been recommended as the optimum process-based model for simulating greenhouse gas (GHG) emissions from Irish soils. Results from the site-specific evaluation of the ECOSSE model for an Irish arable site showed a temporal offset between measurements and model outputs which could not be explained by model parameters, motivating further in-depth analysis of the model. This subsequent analysis indicated that the rate modifiers, which control the release of carbon from different pools in the soil, were functioning as intended, but highlighted issues with the model simulation of soil water. The modelled soil dried out fully when in reality it was above field capacity, attributable to erroneous simulation of evaporation on this well-drained sandy soil. In parallel, a spatial process-based model (GlobalECOSSE) was employed to derive national emissions estimates for multiple GHGs and CO2 equivalents for designated agricultural land uses on the island of Ireland. The justification for using the spatial process-based model was to provide an assessment of a model that had fewer input requirements and operated on a monthly timescale to simulate areal emissions. Re

The Global Land and Marine Observations Database aims to produce a comprehensive land-based meteorological data archive and inventory. This requires the compilation of available information on data from land-based meteorological stations from all known available in situ meteorological data repositories/sources at multiple timescales (e.g. sub-daily, daily, and monthly). During this process the service team members have identified that many of the data sources contain stations with incorrect location coordinates. These stations cannot be included in the processing to be served via the Copernicus Climate Change Service until the issues are satisfactorily resolved. Many of these stations are in regions of the world where a sparsity of climate data currently exists, such as Southeast Asia and South America. As such, resolving these issues would provide important additional climate data, but this is a very labour-intensive task. Therefore, we have developed the Geo-locate project – that enrols the help of undergraduate geography students at Maynooth University, Ireland – to resolve some of the landbased station geolocation issues. To date, we have run two Geo-locate projects: the first in the 2017/2018 academic year and the second in the 2018/2019 academic year. Both iterations have been very successful with 1926 of the 2168 total candidate stations ostensibly resolved, which equates to an 88 % success rate. At the same time, students have gained critical skills that helped to meet the expected pedagogical outcomes of the second-year curriculum, while producing a lasting scientific legacy. We asked the class of 2018/2019 to reflect critically upon the outcomes, and we present the results herein; these results provide important feedback on what students felt that they gained from their participation and how we may improve the experience and learning outcomes in future. We will be continuing to run Geo-locate projects over the next few years. We encourage other organizatio

Soil is a complex material capable of storing and releasing large amounts of carbon, making it an integral part of the global carbon cycle. As soil is included in national inventory assessments where countries quantify their emissions, it is important that estimates of the soil carbon flux are as accurate as possible. Measuring the flux of carbon from every surface on the planet is unrealistic, therefore modelling emissions is the next best method of emissions assessment. Among modelling approaches, process-based modelling allows for the highest specificity of input data. Process-based models split soil carbon into pools with different decay rates influenced by environmental (biotic and abiotic) factors and management. The Estimation of Carbon in Organic Soils – Sequestration and Emissions (ECOSSE) model has previously been recommended as the optimum process-based model for simulating greenhouse gas (GHG) emissions from Irish soils. Results from the site-specific evaluation of the ECOSSE model for an Irish arable site showed a temporal offset between measurements and model outputs which could not be explained by model parameters, motivating further in-depth analysis of the model. This subsequent analysis indicated that the rate modifiers, which control the release of carbon from different pools in the soil, were functioning as intended, but highlighted issues with the model simulation of soil water. The modelled soil dried out fully when in reality it was above field capacity, attributable to erroneous simulation of evaporation on this well-drained sandy soil. In parallel, a spatial process-based model (GlobalECOSSE) was employed to derive national emissions estimates for multiple GHGs and CO2 equivalents for designated agricultural land uses on the island of Ireland. The justification for using the spatial process-based model was to provide an assessment of a model that had fewer input requirements and operated on a monthly timescale to simulate areal emissions. Re

© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Background: Relative to the oral contraceptive pill, uptake of long-acting reversible contraceptive methods (LARCs) in Australia continues to be lower than might be suggested by the evidence on their clinical and economic benefits. Aim: To undertake a critical appraisal of published economic evaluations of LARCs to assess the generalisability of their results to the Australian healthcare context. Materials and Methods: A search of the literature was conducted to identify studies of economic evaluations of LARCs using the Medline, Embase and PubMed databases. The quality of the studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: A total of 1009 citations were screened, from which 20 papers, typically reporting the cost per pregnancy avoided, were reviewed. The overall quality of the studies varied but was generally poor (average score of 62/100). To aid comparisons, results have been grouped under the headings IUS (all hormonal intrauterine systems), IUDs (all non-hormonal intrauterine devices), injectables (all contraceptive injections) and implants (all subdermal contraceptive implants). Overall, the results indicated that LARCs were more effective and less costly than oral contraceptives. Conclusions: Despite evidence that LARCs represent value for money, limitations in study quality and approaches must be taken into account when applying these results to Australia. Differences in healthcare settings aside, LARCs may also have benefits beyond their effect on pregnancy that might be captured in broader analyses, such as cost-benefit analyses using willingness to pay methods. These would capture benefits beyond health, which seem to be particularly relevant to contraception.

© 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists Background: Relative to the oral contraceptive pill, uptake of long-acting reversible contraceptive methods (LARCs) in Australia continues to be lower than might be suggested by the evidence on their clinical and economic benefits. Aim: To undertake a critical appraisal of published economic evaluations of LARCs to assess the generalisability of their results to the Australian healthcare context. Materials and Methods: A search of the literature was conducted to identify studies of economic evaluations of LARCs using the Medline, Embase and PubMed databases. The quality of the studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: A total of 1009 citations were screened, from which 20 papers, typically reporting the cost per pregnancy avoided, were reviewed. The overall quality of the studies varied but was generally poor (average score of 62/100). To aid comparisons, results have been grouped under the headings IUS (all hormonal intrauterine systems), IUDs (all non-hormonal intrauterine devices), injectables (all contraceptive injections) and implants (all subdermal contraceptive implants). Overall, the results indicated that LARCs were more effective and less costly than oral contraceptives. Conclusions: Despite evidence that LARCs represent value for money, limitations in study quality and approaches must be taken into account when applying these results to Australia. Differences in healthcare settings aside, LARCs may also have benefits beyond their effect on pregnancy that might be captured in broader analyses, such as cost-benefit analyses using willingness to pay methods. These would capture benefits beyond health, which seem to be particularly relevant to contraception.

Globally, it is estimated that ~ 1500 Pg C of organic carbon is stored in the top meter of terrestrial soils. This represents the largest terrestrial pool of carbon. Appropriate management of soils, to maintain or increase the soil carbon pool, represents a significant climate change mitigation opportunity. To achieve this, appropriate tools and models are required in order to more accurately estimate soil carbon fluxes with a view to informing and developing more effective land use management strategies. Central to this is the evaluation of models currently in use to estimate soil carbon emissions. In the present study, we evaluate the ECOSSE (Estimating Carbon in Organic Soils – Sequestration and Emissions) model which has its origins in both SUNDIAL and RothC and has been widely used globally to model soil CO2 fluxes across different locations and land-use types on both organic and mineral soils. In contrast to previous studies, the model was found to poorly represent observed soil respiration at the study site, an arable cropland on mineral soil located in south-east Ireland. To isolate potential sources of error, the model was decomposed into its component rate equations or modifiers. This investigation highlighted a deficiency in the model simulated soil water, resulting in significant inhibition of the model simulated CO2 flux relative to the observed data. When measured values of soil water at the site were employed, the model simulated soil respiration improved significantly (r2 of 0.775 vs 0.154). This highlighted model deficiency remains to be evaluated at other sites; however, the research highlights the need for a more comprehensive evaluation of soil carbon models prior to their use in informing policy, particularly models which are employed at larger scales and for climate change projections.

Globally, it is estimated that ~ 1500 Pg C of organic carbon is stored in the top meter of terrestrial soils. This represents the largest terrestrial pool of carbon. Appropriate management of soils, to maintain or increase the soil carbon pool, represents a significant climate change mitigation opportunity. To achieve this, appropriate tools and models are required in order to more accurately estimate soil carbon fluxes with a view to informing and developing more effective land use management strategies. Central to this is the evaluation of models currently in use to estimate soil carbon emissions. In the present study, we evaluate the ECOSSE (Estimating Carbon in Organic Soils – Sequestration and Emissions) model which has its origins in both SUNDIAL and RothC and has been widely used globally to model soil CO2 fluxes across different locations and land-use types on both organic and mineral soils. In contrast to previous studies, the model was found to poorly represent observed soil respiration at the study site, an arable cropland on mineral soil located in south-east Ireland. To isolate potential sources of error, the model was decomposed into its component rate equations or modifiers. This investigation highlighted a deficiency in the model simulated soil water, resulting in significant inhibition of the model simulated CO2 flux relative to the observed data. When measured values of soil water at the site were employed, the model simulated soil respiration improved significantly (r2 of 0.775 vs 0.154). This highlighted model deficiency remains to be evaluated at other sites; however, the research highlights the need for a more comprehensive evaluation of soil carbon models prior to their use in informing policy, particularly models which are employed at larger scales and for climate change projections.

Steadily increasing antifungal drug resistance and persistent high rates of fungal-associated mortality highlight the dire need for the development of novel antifungals. Characterization of inhibitors of one enzyme in the GPI anchor pathway, Gwt1, has generated interest in the exploration of targets in this pathway for further study. Utilizing a chemical genomics-based screening platform referred to as the Candida albicans fitness test (CaFT), we have identified novel inhibitors of Gwt1 and a second enzyme in the glycosylphosphatidylinositol (GPI) cell wall anchor pathway, Mcd4. We further validate these targets using the model fungal organism Saccharomyces cerevisiae and demonstrate the utility of using the facile toolbox that has been compiled in this species to further explore target specific biology. Using these compounds as probes, we demonstrate that inhibition of Mcd4 as well as Gwt1 blocks the growth of a broad spectrum of fungal pathogens and exposes key elicitors of pathogen recognition. Interestingly, a strong chemical synergy is also observed by combining Gwt1 and Mcd4 inhibitors, mirroring the demonstrated synthetic lethality of combining conditional mutants of GWT1 and MCD4. We further demonstrate that the Mcd4 inhibitor M720 is efficacious in a murine infection model of systemic candidiasis. Our results establish Mcd4 as a promising antifungal target and confirm the GPI cell wall anchor synthesis pathway as a promising antifungal target area by demonstrating that effects of inhibiting it are more general than previously recognized., Genome Canada (Firm), Genome Quebec

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Qc 20151211

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Article number: 7297272

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Qc 20151211

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Article number: 7297272

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Article number: 7297272

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Article number: 7297272

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Qc 20151211

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Article number: 7297272

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Qc 20151211

Design of low loss with an enhanced thermal profile power divider/combiner for high power dual-band Radio Frequency (RF) power amplifier applications is given. The practical implementation, low loss and substrate characteristics make this type of combiner ideal for high power microwave applications. The combiner operational frequencies are chosen to operate at 900 MHz and 2.14 GHz, which are common frequencies for concurrent dual band RF power amplifiers. The analytical results are verified with simulation results for various cases and agreement has been observed on all of them., Qc 20151211

the contribution of Naranjo, psychologist, philosopher, father of the "Enneagram Personality System", to a vision totally renewed of the education, in which it is finally recognized to the body, the passion and spirituality the fundamental role. In a perspective that is opposed radically, in a countereducative way, to the patriarchal, mental and oppressive culture of the institutional education diffused in the majority of the world

Copyright © Cambridge University Press 2014. Objectives: When incorporating treatment effect estimates derived from a random-effect meta-analysis it is tempting to use the confidence bounds to determine the potential range of treatment effect. However, prediction intervals reflect the potential effect of a technology rather than the more narrowly defined average treatment effect. Using a case study of robot-assisted radical prostatectomy, this study investigates the impact on a cost-utility analysis of using clinical effectiveness derived from random-effects meta-analyses presented as confidence bounds and prediction intervals, respectively. Methods: To determine the cost-utility of robot-assisted prostatectomy, an economic model was developed. The clinical effectiveness of robot-assisted surgery compared with open and conventional laparoscopic surgery was estimated using meta-analysis of peer-reviewed publications. Assuming treatment effect would vary across studies due to both sampling variability and differences between surgical teams, random-effects meta-analysis was used to pool effect estimates. Results: Using the confidence bounds approach the mean and median ICER was €24,193 and €26,731/QALY (95%CI: €13,752 to €68,861/QALY), respectively. The prediction interval approach produced an equivalent mean and median ICER of €26,920 and €26,643/QALY (95%CI: -€135,244 to €239,166/QALY), respectively. Using prediction intervals, there is a probability of 0.042 that robot-assisted surgery will result in a net reduction in QALYs. Conclusions: Using prediction intervals rather than confidence bounds does not affect the point estimate of the treatment effect. In meta-analyses with significant heterogeneity, the use of prediction intervals will produce wider ranges of treatment effect, and hence result in greater uncertainty, but a better reflection of the effect of the technology.

Copyright © Cambridge University Press 2014. Objectives: When incorporating treatment effect estimates derived from a random-effect meta-analysis it is tempting to use the confidence bounds to determine the potential range of treatment effect. However, prediction intervals reflect the potential effect of a technology rather than the more narrowly defined average treatment effect. Using a case study of robot-assisted radical prostatectomy, this study investigates the impact on a cost-utility analysis of using clinical effectiveness derived from random-effects meta-analyses presented as confidence bounds and prediction intervals, respectively. Methods: To determine the cost-utility of robot-assisted prostatectomy, an economic model was developed. The clinical effectiveness of robot-assisted surgery compared with open and conventional laparoscopic surgery was estimated using meta-analysis of peer-reviewed publications. Assuming treatment effect would vary across studies due to both sampling variability and differences between surgical teams, random-effects meta-analysis was used to pool effect estimates. Results: Using the confidence bounds approach the mean and median ICER was €24,193 and €26,731/QALY (95%CI: €13,752 to €68,861/QALY), respectively. The prediction interval approach produced an equivalent mean and median ICER of €26,920 and €26,643/QALY (95%CI: -€135,244 to €239,166/QALY), respectively. Using prediction intervals, there is a probability of 0.042 that robot-assisted surgery will result in a net reduction in QALYs. Conclusions: Using prediction intervals rather than confidence bounds does not affect the point estimate of the treatment effect. In meta-analyses with significant heterogeneity, the use of prediction intervals will produce wider ranges of treatment effect, and hence result in greater uncertainty, but a better reflection of the effect of the technology.

Medline and Embase were searched for studies comparing robot-assisted radical prostatectomy with open prostatectomy and conventional laparoscopic prostatectomy. Random effects meta-analysis was used to calculate a pooled estimate of effect. The 95% prediction intervals are also reported. One randomized study and 50 observational studies were identified. The results show that compared with open surgery, robot-assisted surgery is associated with fewer positive surgical margins for pT2 tumors (relative risk 0.63, 95% confidence interval 0.49-0.81, P<0.001) and improved outcomes for sexual function at 12months (relative risk 1.60, 95% confidence interval 1.33-1.93, P=<0.001), and, to a lesser extent, urinary function at 12months (relative risk 1.06, 95% confidence interval 1.02-1.11, P<0.01). Compared with conventional laparoscopic prostatectomy, robot-assisted surgery is associated with a slight increase in urinary function at 12months (relative risk 1.09, 95% confidence interval 1.02 to 1.17, P=0.013). The overall methodological quality of the included studies was low, with high levels of heterogeneity. The use of prediction intervals as an aid to decision making in regard to the introduction of this technology is examined. Clinically significant improvements in positive surgical margins rates for pT2 tumors and sexual function at 12months associated with robot-assisted surgery in comparison with open surgery should be interpreted with caution given the limitations of the evidence. Differences between robot-assisted and conventional laparoscopic surgery are minimal. © 2013 The Japanese Urological Association.

Purpose: To review the safety and effectiveness of robot-assisted hysterectomy compared to traditional open and conventional laparoscopic surgery, differentiating radical, simple total with node staging, and simple total hysterectomy. Methods: Medline, Embase, the Cochrane library, and the Journal of Robotic Surgery were searched for controlled trials and observational studies with historic or concurrent controls. Data were pooled using random effects meta-analysis. Results: Compared to open surgery, robot-assisted radical hysterectomy is associated with reduced hospital stay and blood transfusions. For simple total hysterectomy with node staging, robot-assisted surgery is associated with reduced hospital stay, complications, and blood transfusions compared to open surgery. Compared to conventional laparoscopic surgery, robot-assisted simple total hysterectomy with node staging is associated with complications and conversions. Conclusions: Compared to open surgery, robot-assisted hysterectomy offers benefits for reduced length of hospital stay and blood transfusions. The best evidence of improved outcomes is for simple total hysterectomy with node staging. Study quality was poor. © 2013 Springer-Verlag Berlin Heidelberg.

© 2013 The Cochrane Collaboration. Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a leading cause of morbidity and mortality. Screening for AF in asymptomatic patients has been proposed as a way of reducing the burden of the disease by detecting people who would benefit from prophylactic anticoagulation therapy prior to the onset of symptoms. However, for screening to be an effective intervention it must improve the detection of AF and provide benefit for those who are detected earlier as a result of screening. Objectives: The primary objective of this review was to examine whether screening programmes increase the detection of new cases of AF compared to routine practice. The secondary objectives were to identify which combination of screening strategy and patient population is most effective, as well as assessing any safety issues associated with screening, its acceptability within the target population and the costs involved. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE (Ovid) and EMBASE (Ovid) up to March 2012. Other relevant research databases, trials registries and websites were searched up to June 2012. Reference lists of identified studies were also searched for potentially relevant studies and we contacted corresponding authors for information about additional published or unpublished studies that may be relevant. No language restrictions were applied. Selection criteria: Randomised controlled trials, controlled before and after studies and interrupted time series studies comparing screening for AF with routine practice in people aged 40 years and over were eligible. Two authors (PM, CT or MF) independently selected the trials for inclusion. Data collection and analysis: Assessment of risk of bias and data extraction were performed independently by two authors (PM, CT). Odds ratios (OR) and 95% confidence intervals (CI) were used to p

Medline and Embase were searched for studies comparing robot-assisted radical prostatectomy with open prostatectomy and conventional laparoscopic prostatectomy. Random effects meta-analysis was used to calculate a pooled estimate of effect. The 95% prediction intervals are also reported. One randomized study and 50 observational studies were identified. The results show that compared with open surgery, robot-assisted surgery is associated with fewer positive surgical margins for pT2 tumors (relative risk 0.63, 95% confidence interval 0.49-0.81, P<0.001) and improved outcomes for sexual function at 12months (relative risk 1.60, 95% confidence interval 1.33-1.93, P=<0.001), and, to a lesser extent, urinary function at 12months (relative risk 1.06, 95% confidence interval 1.02-1.11, P<0.01). Compared with conventional laparoscopic prostatectomy, robot-assisted surgery is associated with a slight increase in urinary function at 12months (relative risk 1.09, 95% confidence interval 1.02 to 1.17, P=0.013). The overall methodological quality of the included studies was low, with high levels of heterogeneity. The use of prediction intervals as an aid to decision making in regard to the introduction of this technology is examined. Clinically significant improvements in positive surgical margins rates for pT2 tumors and sexual function at 12months associated with robot-assisted surgery in comparison with open surgery should be interpreted with caution given the limitations of the evidence. Differences between robot-assisted and conventional laparoscopic surgery are minimal. © 2013 The Japanese Urological Association.

© 2013 The Cochrane Collaboration. Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is a leading cause of morbidity and mortality. Screening for AF in asymptomatic patients has been proposed as a way of reducing the burden of the disease by detecting people who would benefit from prophylactic anticoagulation therapy prior to the onset of symptoms. However, for screening to be an effective intervention it must improve the detection of AF and provide benefit for those who are detected earlier as a result of screening. Objectives: The primary objective of this review was to examine whether screening programmes increase the detection of new cases of AF compared to routine practice. The secondary objectives were to identify which combination of screening strategy and patient population is most effective, as well as assessing any safety issues associated with screening, its acceptability within the target population and the costs involved. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE (Ovid) and EMBASE (Ovid) up to March 2012. Other relevant research databases, trials registries and websites were searched up to June 2012. Reference lists of identified studies were also searched for potentially relevant studies and we contacted corresponding authors for information about additional published or unpublished studies that may be relevant. No language restrictions were applied. Selection criteria: Randomised controlled trials, controlled before and after studies and interrupted time series studies comparing screening for AF with routine practice in people aged 40 years and over were eligible. Two authors (PM, CT or MF) independently selected the trials for inclusion. Data collection and analysis: Assessment of risk of bias and data extraction were performed independently by two authors (PM, CT). Odds ratios (OR) and 95% confidence intervals (CI) were used to p

Purpose: To review the safety and effectiveness of robot-assisted hysterectomy compared to traditional open and conventional laparoscopic surgery, differentiating radical, simple total with node staging, and simple total hysterectomy. Methods: Medline, Embase, the Cochrane library, and the Journal of Robotic Surgery were searched for controlled trials and observational studies with historic or concurrent controls. Data were pooled using random effects meta-analysis. Results: Compared to open surgery, robot-assisted radical hysterectomy is associated with reduced hospital stay and blood transfusions. For simple total hysterectomy with node staging, robot-assisted surgery is associated with reduced hospital stay, complications, and blood transfusions compared to open surgery. Compared to conventional laparoscopic surgery, robot-assisted simple total hysterectomy with node staging is associated with complications and conversions. Conclusions: Compared to open surgery, robot-assisted hysterectomy offers benefits for reduced length of hospital stay and blood transfusions. The best evidence of improved outcomes is for simple total hysterectomy with node staging. Study quality was poor. © 2013 Springer-Verlag Berlin Heidelberg.

Background: Variant Creutzfeldt-Jakob disease (vCJD) is a rare, progressive fatal noninflammatory neurodegenerative disease. Ireland has the second highest rate of vCJD in the world with an ongoing risk of vCJD transmission through blood transfusion. Prion-removing filters have been developed to reduce the risk of vCJD transmission. This study aimed to evaluate the cost-effectiveness of implementing a policy of prion filtration of red blood cells (RBCs) in the Republic of Ireland. Study design and methods: A cost-effectiveness model was developed to simulate the likelihood of RBC recipients developing clinical vCJD as a result of being transfused with infected RBCs. Model variables were collected from published literature and expert opinion. Costs were estimated based on the processing changes required to implement prion filtration. Results: In the absence of prion filtration, it is estimated that two individuals will develop clinical vCJD arising from RBC transfusions over a 10-year time horizon. The discounted life-years lost will be 18.5 years. With prion filtration, there will be no deaths or life-years lost. The discounted cost of universal prion filtration is â68.2 million over 10 years with a corresponding incremental cost-effectiveness ratio of â3.7 million per life-year gained. In 25.3% of simulations there were no deaths from vCJD infection through infected blood transfusions, irrespective of prion filtration. Conclusion: Prion filtration is considered not cost-effective by traditional measures. Although numerous non-cost-effective blood safety strategies have been implemented in the past, consideration should be given to the most efficient use of finite resources in transfusion medicine. © 2012 American Association of Blood Banks.

Background: Variant Creutzfeldt-Jakob disease (vCJD) is a rare, progressive fatal noninflammatory neurodegenerative disease. Ireland has the second highest rate of vCJD in the world with an ongoing risk of vCJD transmission through blood transfusion. Prion-removing filters have been developed to reduce the risk of vCJD transmission. This study aimed to evaluate the cost-effectiveness of implementing a policy of prion filtration of red blood cells (RBCs) in the Republic of Ireland. Study design and methods: A cost-effectiveness model was developed to simulate the likelihood of RBC recipients developing clinical vCJD as a result of being transfused with infected RBCs. Model variables were collected from published literature and expert opinion. Costs were estimated based on the processing changes required to implement prion filtration. Results: In the absence of prion filtration, it is estimated that two individuals will develop clinical vCJD arising from RBC transfusions over a 10-year time horizon. The discounted life-years lost will be 18.5 years. With prion filtration, there will be no deaths or life-years lost. The discounted cost of universal prion filtration is â68.2 million over 10 years with a corresponding incremental cost-effectiveness ratio of â3.7 million per life-year gained. In 25.3% of simulations there were no deaths from vCJD infection through infected blood transfusions, irrespective of prion filtration. Conclusion: Prion filtration is considered not cost-effective by traditional measures. Although numerous non-cost-effective blood safety strategies have been implemented in the past, consideration should be given to the most efficient use of finite resources in transfusion medicine. © 2012 American Association of Blood Banks.

Echinocandins, the lipopeptide class of glucan synthase inhibitors, are an alternative to ergosterol-synthesis inhibitors to treat candidiasis and aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a natural product screening program for novel types of glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of glucan synthesis. A novel acidic steroid, named arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica. Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as echinocandins, further supporting the idea that arundifungin belongs to a new class of glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of echinocandins and papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus. Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain a sterile fungus belonging to the Leotiales and an undetermined coelomycete).

Echinocandins, the lipopeptide class of glucan synthase inhibitors, are an alternative to ergosterol-synthesis inhibitors to treat candidiasis and aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a natural product screening program for novel types of glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of glucan synthesis. A novel acidic steroid, named arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica. Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as echinocandins, further supporting the idea that arundifungin belongs to a new class of glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of echinocandins and papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus. Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain a sterile fungus belonging to the Leotiales and an undetermined coelomycete).

An LC-MS-MS method was validated for the quantitation of a beta (3) agonist (A) in human urine to support Phase I studies. A was designed to accelerate metabolism for weight reduction. During assay development a significant loss of A was apparent from frozen urine quality control samples. The addition of 0.75% bovine serum albumin (BSA) in urine (v/v) was required to maximize the recovery of A from urine. Urine samples were basified and extracted into methyl t-butyl ether-isopropyl alcohol (90:10, v/v). The organic layer was washed, evaporated, reconstituted, and injected onto a 5 cm, CS HPLC column prior to MS-MS analysis. The standard curve was linear from 5 to 500 ng/ml. Intraday precision for peak area ratios from BSA urine samples at seven separate concentrations over a range of 5-500 ng/ml (n = 5) was <4.0% and calculated concentrations were within 91-115% of nominal concentrations. Interday precision for BSA urine quality control (QC) samples at four separate concentrations (n = 10 of each) was <5.0% and individual calculated concentrations were within 90-111% of nominal concentrations, This work emphasizes that potential metabolites and quality control standards should be prepared and assayed as early as possible in method development., especially before the sample collection section of the clinical protocol is prepared. The methods described here have wide utility to other compounds containing basic benzene sulfonamides and to beta (3) agonist candidates, (C) 2001 Elsevier Science B.V. All rights reserved.

Rats were placed at 28C for a control period of 4 hr prior to treatment with mecamylamine or saline. After injection the rats were divided into two groups with one group remaining at 28C and the other being placed at 15C. Ganglionic blockade with mecamylamine decreased the urinary excretion of norepinephrine and normetanephrine in both groups of rats. 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion fell in the mecamylamine-treated group kept at 28C but rose slightly in the group transferred to 15C. The fall in norepinephrine and normetanephrine excretion, seen after mecamylamine treatment, reflects a decrease in norepinephrine secretion. The increase in MHPG in the cold indicates a rise in the synthesis and intraneuronal degradation of norepinephrine. These results support our earlier postulate that the rate of norepinephrine synthesis is dependent, at least partially, on the ambient temperature and can dissociate itself from the rate of secretion. (Author)

The study demonstrates the influence of ambient temperature on the excretion of epinephrine, norepinephrine, and their major metabolites. As a result of this work it is concluded that norepinephrine secretion increases in a cold environment and decreases during moderate warm exposure. Heat stress, 36 C, however, increases norepinephrine excretion. The rate of norepinephrine synthesis is inversely proportional to the ambient temperature and in three instances in our experiments the quantity of amine formed was not related to the amount secreted. It is thus concluded that the rate of norepinephrine synthesis is dependent, at least partially, on the ambient temperature and can dissociate itself from the rate of norepinephrine secretion. (Author)

Roger Williams University students enrolled in the Architecture and Construction Management programs used new building mapping technology to recommend a rethinking of the Quinta-Gamilin building in Bristol. The building was originally used by the Army Reserve, but is now being turned into a recreation center. Students designed new programatic designs for the building and generated a cost- analysis of the potential designs.

Roger Williams University students enrolled in the Architecture and Construction Management programs used new building mapping technology to recommend a rethinking of the Quinta-Gamilin building in Bristol. The building was originally used by the Army Reserve, but is now being turned into a recreation center. Students designed new programatic designs for the building and generated a cost- analysis of the potential designs.