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Modern psychometric methods make it possible to eliminate nonperforming items and reduce measurement error. Application of these methods to existing outcome measures can reduce variability in scores, and may increase treatment effect sizes in depression treatment trials.
Aims
We aim to determine whether using confirmatory factor analysis techniques can provide better estimates of the true effects of treatments, by conducting secondary analyses of individual patient data from randomised trials of antidepressant therapies.
Method
We will access individual patient data from antidepressant treatment trials through Clinicalstudydatarequest.com and Vivli.org, specifically targeting studies that used the Hamilton Rating Scale for Depression (HRSD) as the outcome measure. Exploratory and confirmatory factor analytic approaches will be used to determine pre-treatment (baseline) and post-treatment models of depression, in terms of the number of factors and weighted scores of each item. Differences in the derived factor scores between baseline and outcome measurements will yield an effect size for factor-informed depression change. The difference between the factor-informed effect size and each original trial effect size, calculated with total HRSD-17 scores, will be determined, and the differences modelled with meta-analytic approaches. Risk differences for proportions of patients who achieved remission will also be evaluated. Furthermore, measurement invariance methods will be used to assess potential gender differences.
Conclusions
Our approach will determine whether adopting advanced psychometric analyses can improve precision and better estimate effect sizes in antidepressant treatment trials. The proposed methods could have implications for future trials and other types of studies that use patient-reported outcome measures.
The validity of network observations is sometimes of concern in empirical studies, since observed networks are prone to error and may not represent the population of interest. This lack of validity is not just a result of random measurement error, but often due to systematic bias that can lead to the misinterpretation of actors’ preferences of network selections. These issues in network observations could bias the estimation of common network models (such as those pertaining to influence and selection) and lead to erroneous statistical inferences. In this study, we proposed a simulation-based sensitivity analysis method that can evaluate the robustness of inferences made in social network analysis to six forms of selection mechanisms that can cause biases in network observations—random, homophily, anti-homophily, transitivity, reciprocity, and preferential attachment. We then applied this sensitivity analysis to test the robustness of inferences for social influence effects, and we derived two sets of analytical solutions that can account for biases in network observations due to random, homophily, and anti-homophily selection.
There is a growing consensus in the literature that governance architectures matter. However, we lack sufficient knowledge about their emergence, dynamics and impacts. This concluding chapter summarizes all insights in the book Architectures of Earth System Governance, and emphasizes how this book has made a scientific contribution by enhancing conceptual clarity, synthesizing a decade of intense research, and charting directions for future research. The book has made at least one point clear: the ‘architecture lens’ offers a bird’s-eye view on the global governance landscape that is highly valuable in explaining outcomes of world politics. The architectures matter in how institutions interact with others, how institutions are entangled with others in larger regime complexes and how institutions are affected by broader architectures that are more or less fragmented or polycentric. In this concluding chapter, we also illustrate how such key insights gained could inform a set of transformative policy proposals regarding the architecture of earth system governance.
Hydrilla is an invasive aquatic plant that has rapidly spread through many inland water bodies across the globe by outcompeting native aquatic plants. The negative impacts of hydrilla invasion have become a concern for water resource management authorities, power companies, and environmental scientists. The early detection of hydrilla infestation is very important to reduce the costs associated with control and removal efforts of this invasive species. Therefore, in this study, we aimed to develop a tool for rapid, frequent, and large-scale monitoring and predicting spatial extent of hydrilla habitat. This was achieved by integrating in situ and Landsat 8 Operational Land Imager satellite data for Lake J. Strom Thurmond, the largest US Army Corps of Engineers lake east of the Mississippi River, located on the border of Georgia and South Carolina border. The predictive model for presence of hydrilla incorporated radiometric and physical measurements, including remote-sensing reflectance, Secchi disk depth (SDD), light-attenuation coefficient (Kd), maximum depth of colonization (Zc), and percentage of light available through the water column (PLW). The model-predicted ideal habitat for hydrilla featured high SDD, Zc, and PLW values, low values of Kd. Monthly analyses based on satellite images showed that hydrilla starts growing in April, reaches peak coverage around October, begins retreating in the following months, and disappears in February. Analysis of physical and meteorological factors (i.e., water temperature, surface runoff, net inflow, precipitation) revealed that these parameters are closely associated with hydrilla extent. Management agencies can use these results not only to plan removal efforts but also to evaluate and adapt their current mitigation efforts.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Methods
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Results
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
Conclusion
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
A clean hot-water drill was used to gain access to Subglacial Lake Whillans (SLW) in late January 2013 as part of the Whillans Ice Stream Subglacial Access Research Drilling (WISSARD) project. Over 3 days, we deployed an array of scientific tools through the SLW borehole: a downhole camera, a conductivity–temperature–depth (CTD) probe, a Niskin water sampler, an in situ filtration unit, three different sediment corers, a geothermal probe and a geophysical sensor string. Our observations confirm the existence of a subglacial water reservoir whose presence was previously inferred from satellite altimetry and surface geophysics. Subglacial water is about two orders of magnitude less saline than sea water (0.37–0.41 psu vs 35 psu) and two orders of magnitude more saline than pure drill meltwater (<0.002 psu). It reaches a minimum temperature of –0.55~C, consistent with depression of the freezing point by 7.019 MPa of water pressure. Subglacial water was turbid and remained turbid following filtration through 0.45 µm filters. The recovered sediment cores, which sampled down to 0.8 m below the lake bottom, contained a macroscopically structureless diamicton with shear strength between 2 and 6 kPa. Our main operational recommendation for future subglacial access through water-filled boreholes is to supply enough heat to the top of the borehole to keep it from freezing.
The large diversity of farms and farming systems in sub-Saharan Africa calls for agricultural improvement options that are adapted to the context in which smallholder farmers operate. The socio-ecological niche concept incorporates the agro-ecological, socio-cultural, economic and institutional dimensions and the multiple levels of this context in order to identify which options fit best. In this paper, we illustrate how farming systems analysis, following the DEED cycle of Describe, Explain, Explore and Design, and embedding co-learning amongst researchers, farmers and other stakeholders, helps to operationalize the socio-ecological niche concept. Examples illustrate how farm typologies, detailed farm characterization and on-farm experimental work, in combination with modelling and participatory approaches inform the matching of options to the context at regional, village, farm and field level. Recommendation domains at these gradually finer levels form the basis for gradually more detailed baskets of options from which farmers and other stakeholders may choose, test and adjust to their specific needs. Tailored options identified through the DEED cycle proof to be more relevant, feasible and performant as compared to blanket recommendations in terms of both researcher and farmer-identified criteria. As part of DEED, on-farm experiments are particularly useful in revealing constraints and risks faced by farmers. We show that targeting options to the niches in which they perform best, helps to reduce this risk. Whereas the conclusions of our work about the potential for improving smallholders’ livelihoods are often sobering, farming systems analysis allows substantiating the limitations of technological options, thus highlighting the need for enabling policies and institutions that may improve the larger-scale context and increase the uptake potential of options.
Since few studies have examined the effectiveness of therapies for subcortical vascular dementia, treatment guidelines are not available. Current patterns in the treatment of such dementias have not been studied.
Objective:
To determine the practice patterns of Canadian specialists for the treatment of subcortical vascular dementia, and to survey their opinions regarding issues which are important in the design of a randomized controlled trial (RCT) in this field.
Design:
National survey of all specialists certified in Neurology or Geriatric Medicine.
Results:
Of responding physicians (78%) prescribed antithrombotic therapy for patients with vascular dementia. Most begin treatment with aspirin 325 mg daily (64%). The next three most common initial treatments were; no pharmacotherapy (12%), aspirin 650 mg daily (11%), and aspirin 1300 mg daily (11%). If the dementia continued to progress despite initial therapy, the treatment options were more varied. Most specialists (69%) believed that an RCT to assess the efficacy of aspirin in vascular dementia is warranted. The majority (69%) also felt that serial neuroimaging would be required for participants in such a trial, with magnetic resonance imaging being cited most frequently (41%). The majority of specialists considered three years as the minimum durationb for such a trial.
Conclusions:
Specialist physician practice patterns vary significantly for the treatment of patients with subcortical vascular dementia. Most physicians believe that an RCT testing the efficacy of aspirin in this condition is required. However, before such a trial can be conducted, many methodological difficulties need to be addressed.
The ways in which productivity, stability, population interactions, and community structure are regulated in ecosystems have been a central focus of ecology for over a century. At large spatial scales, major insights into these dynamics have been principally derived from analyses of changes induced from hunting, harvesting, and agricultural practices – so-called “natural experiments.” In terrestrial ecosystems estimates of the fraction of land transformed or degraded by human activity fall within the range of 39 to 75% (Vitousek et al., 1997; Ellis et al., 2010). Equally profound is the reality that up to 75% of the global oceans and in particular the continental shelf, transitional slope water areas, and reef habitats have been strongly impacted by human activity (Halpern et al., 2008).
One of the most widely studied human impacts has been the over-exploitation of large-bodied species. Berger et al. (2001) estimated that the spatial distribution of large mammalian carnivores that once played a dominant role in terrestrial ecosystems has declined by 95–99%. In the global oceans large predatory fish biomass may be as low as 10% of pre-industrial levels (Myers and Worm, 2003). These changes have created a vertical compaction and blunting of the trophic pyramid (Duffy, 2003; Chapter 14, this volume). On a global scale, these losses are attributable to a positive association between body size and sensitivity to population declines experienced by larger species which exhibit a greater susceptibility to decline or collapse as a consequence of their lower population densities, greater times to maturity, lower clutch sizes, and larger home ranges (Schipper et al., 2008). This reduction in the abundance of apex predators has led to abnormally high densities of their former prey in a wide range of ecosystems, which has, in turn, resulted in sometimes catastrophic changes in the ecosystems occupied. This has led some to conclude that large-bodied species are essential to the maintenance of ecosystem structure and stability (Hildrew et al., 2007; Estes et al., 2011).
Current guidelines emphasize that emergency department (ED) patients at low risk for potential ischemic chest pain cannot be discharged without extensive investigations or hospitalization to minimize the risk of missing acute coronary syndrome (ACS). We sought to derive and validate a prediction rule that permitted 20 to 30% of ED patients without ACS safely to be discharged within 2 hours withoutfurther provocative cardiac testing.
Methods:
This prospective cohort study enrolled 1,669 chest pain patients in two blocks in 2000–2003 (development cohort) and 2006 (validation cohort). The primary outcome was 30-day ACS diagnosis. A recursive partitioning model incorporated reliable and predictive cardiac risk factors, pain characteristics, electrocardiographic findings, and cardiac biomarker results.
Results:
In the derivation cohort, 165 of 763 patients (21.6%) had a 30-day ACS diagnosis. The derived prediction rule was 100.0% sensitive and 18.6% specific. In the validation cohort, 119 of 906 patients (13.1%) had ACS, and the prediction rule was 99.2% sensitive (95% CI 95.4–100.0) and 23.4% specific (95% CI 20.6–26.5). Patients have a very low ACS risk if arrival and 2-hour troponin levels are normal, the initial electrocardiogram is nonischemic, there is no history of ACS or nitrate use, age is < 50 years, and defined pain characteristics are met. The validation of the rule was limited by the lack of consistency in data capture, incomplete follow-up, and lack of evaluation of the accuracy, comfort, and clinical sensibility of this clinical decision rule.
Conclusion:
The Vancouver Chest Pain Rule may identify a cohort of ED chest pain patients who can be safelydischarged within 2 hours without provocative cardiac testing. Further validation across other centres with consistent application and comprehensive and uniform follow-up of all eligible and enrolled patients, in addition to measuring and reporting the accuracy of and comfort level with applying the rule and the clinical sensibility, should be completed prior to adoption and implementation.
This study tested the hypothesis that phenylbutazone would block the exercise-induced increase in cytokine markers of inflammation in blood. Blood samples were obtained from unfit Standardbred mares (age 10 ± 4 years, ~500 kg) before and after three different trials (standing control (CON), n = 9; exercise with phenylbutazone (EX-bute), n = 9; and exercise with water, n = 9). Comparisons were made for data collected in three trials, one where each horse underwent an incremental exercise test (graded exercise test (GXT)) where they were administered water as a placebo, a GXT following phenylbutazone administration (2 g given orally 2 h before the GXT) or standing parallel control where they stood quietly in stalls. During the GXT, horses ran on a treadmill (1 m s− 1 increases each min until fatigue, 6% grade). Blood samples were obtained 30 min before exercise, immediately after exercise and at 0.5, 1, 2, 4 and 24 h post-GXT or at matched time points during the parallel control trials. Samples were analysed using real-time PCR for measurement of mRNA expression of interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 in samples collected during all three trials, and for IL-1 and IL-10 in samples collected for the CON and EX-bute trials. Data were analysed using ANOVA for repeated measures, and where appropriate, post hoc separation of means utilized the Student–Newman–Keuls test. The null hypothesis was rejected when P < 0.05. There were no changes (P>0.05) in IL-1, IL-6, IFN-γ or TNF-α during CON or following phenylbutazone administration. During the water trial, exercise resulted in significant increases in IFN-γ, IL-1 and TNF-α. It was concluded that high-intensity exercise results in a transient increase in the expression of inflammatory cytokines in blood that is blocked when phenylbutazone is administered to horses.
Human Capital and Institutions is concerned with human capital in its many dimensions and brings to the fore the role of political, social, and economic institutions in human capital formation and economic growth. Written by leading economic historians, including pioneers in historical research on human capital, the chapters in this text offer a broad-based view of human capital in economic development. The issues they address range from nutrition in pre-modern societies to twentieth-century advances in medical care; from the social institutions that provided temporary relief to workers in the middle and lower ranges of the wage scale to the factors that affected the performance of those who reached the pinnacle in business and art; and from political systems that stifled the advance of literacy to those that promoted public and higher education. Just as human capital has been a key to economic growth, so has the emergence of appropriate institutions been a key to the growth of human capital.
Slavery in the Development of the Americas brings together work from leading historians and economic historians of slavery. The essays cover various aspects of slavery and the role of slavery in the development of the southern United States, Brazil, Cuba, the French and Dutch Caribbean, and elsewhere in the Americas. Some essays explore the emergence of the slave system, and others provide important insights about the operation of specific slave economics. There are reviews of slave markets and prices, and discussions of the efficiency and distributional aspects of slavery. Perspectives are brought on the transition from slavery and subsequent adjustments, and the volume contains the work of prominent scholars, many of whom have been pioneers in the study of slavery in the Americas.
Stanley Engerman and Kenneth Sokoloff have been leaders in renewing interest in institutions and their impact on economic development. The papers in this volume are concerned with human capital in its many dimensions, and bring to fore the role of political, social, and economic institutions in human capital formation and economic growth. The papers address a broad range of issues, from nutrition in pre-modern societies to twentieth-century advances in medical care, from the institutions that concerned workers in the middle and lower ranges of the wage scale to the factors that affected the performance of those who reached the pinnacle in business and art, and from political systems that stifled the advance of literacy to those that promoted public and higher education. Just as human capital has been a key to economic growth, so has the emergence of appropriate institutions been a key to human capital formation. It is this theme that underlies the papers in this volume.
Along with Stan Engerman, Robert Fogel pioneered the use of anthropometric evidence to study economic growth, and helped expand our view of human capital. Formal schooling, apprenticeship programs, specialized job training in the workplace, and learning-by-doing all raise productivity, but other forms of human capital investment are also important. The notion that health and physical size and strength can affect labor productivity is not new, but Fogel has brought these forms of human capital to center stage.