Discrete Improvement in Racial Disparity in Survival among Patients with Stage IV Colorectal Cancer: a 21-Year Population-Based Analysis

Purpose Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent. Patients and Methods Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988–2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses. Results Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p<0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991–1.000) per year (p=0.03). Conclusion A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

Time-Series Panel Analysis (TSPA): Multivariate Modeling of Temporal Associations in Psychotherapy Process.

Objective: Processes occurring in the course of psychotherapy are characterized by the simple fact that they unfold in time and that the multiple factors engaged in change processes vary highly between individuals (idiographic phenomena). Previous research, however, has neglected the temporal perspective by its traditional focus on static phenomena, which were mainly assessed at the group level (nomothetic phenomena). To support a temporal approach, the authors introduce time-series panel analysis (TSPA), a statistical methodology explicitly focusing on the quantification of temporal, session-to-session aspects of change in psychotherapy. TSPA-models are initially built at the level of individuals and are subsequently aggregated at the group level, thus allowing the exploration of prototypical models. Method: TSPA is based on vector auto-regression (VAR), an extension of univariate auto-regression models to multivariate time-series data. The application of TSPA is demonstrated in a sample of 87 outpatient psychotherapy patients who were monitored by postsession questionnaires. Prototypical mechanisms of change were derived from the aggregation of individual multivariate models of psychotherapy process. In a 2nd step, the associations between mechanisms of change (TSPA) and pre- to postsymptom change were explored. Results: TSPA allowed a prototypical process pattern to be identified, where patient's alliance and self-efficacy were linked by a temporal feedback-loop. Furthermore, therapist's stability over time in both mastery and clarification interventions was positively associated with better outcomes. Conclusions: TSPA is a statistical tool that sheds new light on temporal mechanisms of change. Through this approach, clinicians may gain insight into prototypical patterns of change in psychotherapy.

Global phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineages.

The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated Streptococcus pneumoniae (Non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if Non-Ec-Sp evolve sporadically, if they have high antibiotic non-susceptiblity rates and a unique, specific gene content. Here, whole genome sequencing of 131 Non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multi-locus sequences types ST344 (n=39) and ST448 (n=40). All ST344 and nine ST448 isolates had high non-susceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic Non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic Non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic Non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P=0.005). In contrast, sporadic Non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, Non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of pneumococcal conjugate vaccines, Non-Ec-Sp may become more prevalent.

The Career Satisfaction Scale: Longitudinal measurement invariance and latent growth analysis

The present research analyses the adequacy of the widely used Career Satisfaction Scale (CSS; Greenhaus, Parasuraman, & Wormley, 1990) for measuring change over time. We used data of a sample of 1,273 professionals over a 5-year time period. First, we tested longitudinal measurement invariance of the CSS. Second, we analysed changes in career satisfaction by means of multiple indicator latent growth modelling (MLGM). Results revealed that the CSS can be reliably used in mean change analyses. Altogether, career satisfaction was relatively stable over time; however, we found significant variance in intra-individual growth trajectories and a negative correlation between the initial level of and changes in career satisfaction. Professionals who were initially highly satisfied became less satisfied over time. Theoretical and practical implications with respect to the construct of career satisfaction and its development over time (i.e., alpha, beta, and gamma change) are discussed.

Assessing the Potential of Multiple Imputation in Sequence Analysis

Sequence analysis and optimal matching are useful heuristic tools for the descriptive analysis of heterogeneous individual pathways such as educational careers, job sequences or patterns of family formation. However, to date it remains unclear how to handle the inevitable problems caused by missing values with regard to such analysis. Multiple Imputation (MI) offers a possible solution for this problem but it has not been tested in the context of sequence analysis. Against this background, we contribute to the literature by assessing the potential of MI in the context of sequence analyses using an empirical example. Methodologically, we draw upon the work of Brendan Halpin and extend it to additional types of missing value patterns. Our empirical case is a sequence analysis of panel data with substantial attrition that examines the typical patterns and the persistence of sex segregation in school-to-work transitions in Switzerland. The preliminary results indicate that MI is a valuable methodology for handling missing values due to panel mortality in the context of sequence analysis. MI is especially useful in facilitating a sound interpretation of the resulting sequence types.

Sustainability principles put into practice: case studies of network analysis in Swiss climate change adaptation

Climate adaptation policies increasingly incorporate sustainability principles into their design and implementation. Since successful adaptation by means of adaptive capacity is recognized as being dependent upon progress toward sustainable development, policy design is increasingly characterized by the inclusion of state and non-state actors (horizontal actor integration), cross-sectoral collaboration, and inter-generational planning perspectives. Comparing four case studies in Swiss mountain regions, three located in the Upper Rhone region and one case from western Switzerland, we investigate how sustainability is put into practice. We argue that collaboration networks and sustainability perceptions matter when assessing the implementation of sustainability in local climate change adaptation. In other words, we suggest that adaptation is successful where sustainability perceptions translate into cross-sectoral integration and collaboration on the ground. Data about perceptions and network relations are assessed through surveys and treated via cluster and social network analysis.

Revealing regional deforestation dynamics in north-eastern Madagascar - Insights from multi-temporal land cover change analysis

The north-eastern escarpment of Madagascar harbours the island’s last remaining large-scale humid forest massifs surrounded by a small-scale agricultural mosaic. There is high deforestation, commonly thought to be caused by shifting cultivation practiced by local land users to produce upland rice. However, little is known about the dynamics between forest and shifting cultivation systems at a regional level. Our study presents a first attempt to quantify changes in the extent of forest and different agricultural land cover classes, and to identify the main dynamics of land cover change for two intervals, 1995–2005 and 2005–2011. Over the 16-year study period, the speed of forest loss increased, the total area of upland rice production remained almost stable, and the area of irrigated rice fields slightly increased. While our findings seem to confirm a general trend of land use intensification, deforestation through shifting cultivation is still on the rise. Deforestation mostly affects the small forest fragments interspersed in the agricultural mosaic and is slowly leading to a homogenization of the landscape. These findings have important implications for future interventions to slow forest loss in the region, as the processes of agricultural expansion through shifting cultivation versus intensified land use cannot per se be considered mutually exclusive.

Towards a spatial understanding of trade-offs in sustainable development: A meso-scale analysis of the nexus between land use, poverty, and environment in the Lao PDR

In land systems, equitably managing trade-offs between planetary boundaries and human development needs represents a grand challenge in sustainability oriented initiatives. Informing such initiatives requires knowledge about the nexus between land use, poverty, and environment. This paper presents results from Lao PDR, where we combined nationwide spatial data on land use types and the environmental state of landscapes with village-level poverty indicators. Our analysis reveals two general but contrasting trends. First, landscapes with paddy or permanent agriculture allow a greater number of people to live in less poverty but come at the price of a decrease in natural vegetation cover. Second, people practising extensive swidden agriculture and living in intact environments are often better off than people in degraded paddy or permanent agriculture. As poverty rates within different landscape types vary more than between landscape types, we cannot stipulate a land use–poverty–environment nexus. However, the distinct spatial patterns or configurations of these rates point to other important factors at play. Drawing on ethnicity as a proximate factor for endogenous development potentials and accessibility as a proximate factor for external influences, we further explore these linkages. Ethnicity is strongly related to poverty in all land use types almost independently of accessibility, implying that social distance outweighs geographic or physical distance. In turn, accessibility, almost a precondition for poverty alleviation, is mainly beneficial to ethnic majority groups and people living in paddy or permanent agriculture. These groups are able to translate improved accessibility into poverty alleviation. Our results show that the concurrence of external influences with local—highly contextual—development potentials is key to shaping outcomes of the land use–poverty–environment nexus. By addressing such leverage points, these findings help guide more effective development interventions. At the same time, they point to the need in land change science to better integrate the understanding of place-based land indicators with process-based drivers of land use change.

Economic analysis of soil conservation: Case studies from the highlands of Amhara Region, Ethiopia

Soil degradation is widespread in the Ethiopian Highlands. Its negative impacts on soil productivity contribute to the extreme poverty of the rural population. Soil conservation is propagated as a means of reducing soil erosion, however, it is a costly investment for small-scale farming households. The present study is an attempt to show whether or not selected mechanical Soil and Water Conservation (SWC) technologies are profitable from a farmer’s point of view. A financial Cost-Benefit Analysis (CBA) is carried out to assess whether or not the considered SWC technologies are profitable from a farmer’s point of view. The CBA is supplemented by an evaluation of aspects from the economic and institutional environment. Whether or not soil conservation is profitable from a farmer’s point of view depends on a broad range of factors from the ecological, economic, political, institutional and socio-cultural sphere and also depends on the technology and the prevailing farming system. Because these factors are closely interlinked, it is often not sufficient to change or influence one to make SWC profitable. Several recommendations are formulated with regard to improving the profitability of SWC investments from a farmer’s point of view. Because the reasons for unsustainable resource use are manifold and highly interlinked, only a multi-stakeholder, multi-level and multi-objective approach is likely to offer solutions that address the underlying problems adequately.

Temporal change in prevalence and complications of uveitis associated with juvenile idiopathic arthritis:data from a cross-sectional analysis of a prospective nationwide study

OBJECTIVES To analyse the nationwide prevalence of uveitis in JIA and its complications over a whole decade. METHODS We conducted a prospective, observational and cross-sectional study including all JIA patients from a National Paediatric Rheumatological Database (NPRD) with a uveitis add-on module in Germany (2002-2013). Temporal changes in uveitis prevalence, related secondary complications and anti-inflammatory medication were evaluated. RESULTS A total of 60 centres including 18,555 JIA patients (mean 3,863 patients/year, SD=837) were documented in the NPRD between 2002 and 2013. The mean age of the patients was 11.4±4.6 years, their mean disease duration 4.4±3.7 years. Among them, 66.9% were female and 51.7% ANA positive. Patients' mean age at arthritis onset was 6.9±4.5 years. Treatment rates with synthetic and biological DMARDs increased during the observation period (sDMARD: 39.8% to 47.2%, bDMARD: 3.3% to 21.8%). Uveitis prevalence decreased significantly from 2002 to 2013 (13.0% to 11.6%, OR = 0.98, p=0.015). The prevalence of secondary uveitis complications also decreased significantly between 2002 and 2013 (33.6% to 23.9%, OR=0.94, p<0.001). Among the complications, the most common ones were posterior synechiae, cataract and band keratopathy. A significant increase in achieving uveitis inactivity was observed at 30.6% in 2002 and 65.3% in 2013 (OR=1.15, p<0.001). CONCLUSIONS Uveitis prevalence and complications significantly decreased between 2002 and 2013. This may be associated with a more frequent use of DMARDs.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women at High Risk for Atherothrombosis: From the Women in Innovation and Drug-Eluting Stents Collaborative Patient-Level Pooled Analysis

BACKGROUND The safety and efficacy of new-generation drug-eluting stents (DES) in women with multiple atherothrombotic risk (ATR) factors is unclear. METHODS AND RESULTS We pooled patient-level data for women enrolled in 26 randomized trials. Study population was categorized based on the presence or absence of high ATR, which was defined as having history of diabetes mellitus, prior percutaneous or surgical coronary revascularization, or prior myocardial infarction. The primary end point was major adverse cardiovascular events defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Out of 10 449 women included in the pooled database, 5333 (51%) were at high ATR. Compared with women not at high ATR, those at high ATR had significantly higher risk of major adverse cardiovascular events (15.8% versus 10.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.34-1.75; P=0.006) and all-cause mortality. In high-ATR risk women, the use of new-generation DES was associated with significantly lower risk of 3-year major adverse cardiovascular events (adjusted hazard ratio: 0.69; 95% confidence interval: 0.52-0.92) compared with early-generation DES. The benefit of new-generation DES on major adverse cardiovascular events was uniform between high-ATR and non-high-ATR women, without evidence of interaction (Pinteraction=0.14). At landmark analysis, in high-ATR women, stent thrombosis rates were comparable between DES generations in the first year, whereas between 1 and 3 years, stent thrombosis risk was lower with new-generation devices. CONCLUSIONS Use of new-generation DES even in women at high ATR is associated with a benefit consistent over 3 years of follow-up and a substantial improvement in very-late thrombotic safety.

CYTOGENETIC AND DNA CONTENT ANALYSIS IN MULTIPLE MYELOMA

In this dissertation, the cytogenetic characteristics of bone marrow cells from 41 multiple myeloma patients were investigated. These cytogenetic data were correlated with the total DNA content as measured by flow cytometry. Both the cytogenetic information and DNA content were then correlated with clinical data to determine if diagnosis and prognosis of multiple myeloma could be improved.^ One hundred percent of the patients demonstrated abnormal chromosome numbers per metaphase. The average chromosome number per metaphase ranged from 42 to 49.9, with a mean of 44.99. The percent hypodiploidy ranged from 0-100% and the percent hyperdiploidy from 0-53%. Detailed cytogenetic analyses were very difficult to perform because of the paucity of mitotic figures and the poor chromosome morphology. Thus, detailed chromosome banding analysis on these patients was impossible.^ Thirty seven percent of the patients had normal total DNA content, whereas 63% had abnormal amounts of DNA (one patient with less than normal amounts and 25 patients with greater than normal amounts of DNA).^ Several clinical parameters were used in the statistical analyses: tumor burden, patient status at biopsy, patient response status, past therapy, type of treatment and percent plasma cells. Only among these clinical parameters were any statistically significant correlations found: pretreatment tumor burden versus patient response, patient biopsy status versus patient response and past therapy versus patient response.^ No correlations were found between percent hypodiploid, diploid, hyperdiploid or DNA content, and the patient response status, nor were any found between those patients with: (a) normal plasma cells, low pretreatment tumor mass burden and more than 50% of the analyzed metaphases with 46 chromosomes; (b) normal amounts of DNA, low pretreatment tumor mass burden and more than 50% of the metaphases with 46 chromosomes; (c) normal amounts of DNA and normal quantities of plasma cells; (d) abnormal amounts of DNA, abnormal amounts of plasma cells, high pretreatment tumor mass burden and less than 50% of the metaphases with 46 chromosomes.^ Technical drawbacks of both cytogenetic and DNA content analysis in these multiple myeloma patients are discussed along with the lack of correlations between DNA content and chromosome number. Refined chromosome banding analysis awaits technical improvements before we can understand which chromosome material (if any) makes up the "extra" amounts of DNA in these patients. None of the correlations tested can be used as diagnostic or prognostic aids for multiple myeloma. ^