An economic evaluation of schizophrenia–1991

In 1991, the costs for schizophrenia, which has a lifetime prevalence of 1.5% among adult Americans, totaled $65 billion. Costs were broken down into their direct and indirect components. Direct costs, which totaled$19 billion dollars, consisted of treatment-related expenditures such as those for inpatients and outpatients, as well as nontreatment-related expenditures such as those for the criminal justice system used by individuals with schizophrenia. The direct costs were fairly similar to those of other recent estimates of the cost of schizophrenia. Indirect costs, which were $46 billion dollars, included the lost productivity of both wage earners ($24 billion) and homemakers ($4.5 billion), individuals who were in institutions ($4.5 billion) or who had committed suicide ($7 billion), and caregivers who took care of schizophrenic family members ($7 billion). Our method for calculating the indirect costs was slightly different than methods used in prior studies, which may account for our estimates being higher. The method for determining each expenditure is provided, and the implications of these staggering costs are discussed

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Large detrital zircon data set investigation and provenance mapping: Local versus regional and continental sediment sources before, during, and after Ancestral Rocky Mountain deformation

The increasing number and size of detrital geochronology data sets offer new opportunities for increased accuracy and resolution of sediment routing models. However, the new opportunities come coupled with challenges in large data integration and visualization. We address these challenges by outlining two novel approaches that aid in analyzing and interpreting large detrital geochronology data sets: (1) combination of bottom-up and top-down detrital zircon source modeling, and (2) sediment provenance mapping. Combining source-modeling methods provides guidance in identifying empirical detrital zircon sources and determining source proportions. Provenance mapping integrates source proportions from modeling results and complimentary geologic data (e.g., paleocurrents, paleogeography, and stratal thickness maps) to extrapolate provenance information through areas with sparse or ambiguous data, thus mitigating issues of data distribution heterogeneity. Sediment provenance maps also provide a synoptic view of data that, along with detrital zircon source modeling, aids in circumventing lengthy descriptions of individual age modes for data sets containing hundreds of samples, which can obscure underlying trends in the data. We apply this approach to late Paleozoic-early Mesozoic strata, using 329 published and new U-Pb detrital zircon samples, and document five sediment-routing episodes in the core zone of intraplate deformation in western Laurentia (i.e., the Ancestral Rocky Mountains (ARM)). The transitions between these episodes are defined by changes in sediment source distribution, which are illustrated by provenance maps that show (1) the degree and extent of ARM basin isolation from transcontinental sediment sources and (2) ARM-driven changes in transcontinental sediment routing systems. We map possible sediment pathways of distally derived sediment around the ARM core, illustrating that ARM uplifts diverted transcontinental systems around areas of intense intraplate deformation. Further, the evolution of sediment routing in western Laurentia before, during, and after ARM deformation provides an example of the interaction between transcontinental sediment routing and intraplate deformation. © 2023 The Authors. Gold Open Access: This paper is published under the terms of the CC-BY license. All Rights Reserved.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Visual genomics analysis studio as a tool to analyze multiomic data

Type B adverse drug reactions (ADRs) are iatrogenic immune-mediated syndromes with mechanistic etiologies that remain incompletely understood. Some of the most severe ADRs, including delayed drug hypersensitivity reactions, are T-cell mediated, restricted by specific human leukocyte antigen risk alleles and sometimes by public or oligoclonal T-cell receptors (TCRs), central to the immunopathogenesis of tissue-damaging response. However, the specific cellular signatures of effector, regulatory, and accessory immune populations that mediate disease, define reaction phenotype, and determine severity have not been defined. Recent development of single-cell platforms bringing together advances in genomics and immunology provides the tools to simultaneously examine the full transcriptome, TCRs, and surface protein markers of highly heterogeneous immune cell populations at the site of the pathological response at a single-cell level. However, the requirement for advanced bioinformatics expertise and computational hardware and software has often limited the ability of investigators with the understanding of diseases and biological models to exploit these new approaches. Here we describe the features and use of a state-of-the-art, fully integrated application for analysis and visualization of multiomic single-cell data called Visual Genomics Analysis Studio (VGAS). This unique user-friendly, Windows-based graphical user interface is specifically designed to enable investigators to interrogate their own data. While VGAS also includes tools for sequence alignment and identification of associations with host or organism genetic polymorphisms, in this review we focus on its application for analysis of single-cell TCR–RNA–Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-seq, enabling holistic cellular characterization by unbiased transcriptome and select surface proteome. Critically, VGAS does not require user-directed coding or access to high-performance computers, instead incorporating performance-optimized hidden code to provide application-based fast and intuitive tools for data analyses and production of high-resolution publication-ready graphics on standard specification laptops. Specifically, it allows analyses of comprehensive single-cell TCR sequencing (scTCR-seq) data, detailing (i) functional pairings of α–β heterodimer TCRs, (ii) one-click histograms to display entropy and gene rearrangements, and (iii) Circos and Sankey plots to visualize clonality and dominance. For unbiased single-cell RNA sequencing (scRNA-seq) analyses, users extract cell transcriptome signatures according to global structure via principal component analysis, t-distributed stochastic neighborhood embedding, or uniform manifold approximation and projection plots, with overlay of scTCR-seq enabling identification and selection of the immunodominant TCR-expressing populations. Further integration with similar sequence-based detection of surface protein markers using oligo-labeled antibodies (CITE-seq) provides comparative understanding of surface protein expression, with differential gene or protein analyses visualized using volcano plot or heatmap functions. These data can be compared to reference cell atlases or suitable controls to reveal discrete disease-specific subsets, from epithelial to tissue-resident memory T-cells, and activation status, from senescence through exhaustion, with more finite transcript expression displayed as violin and box plots. Importantly, guided tutorial videos are available, as are regular application updates based on the latest advances in bioinformatics and user feedback

USE OF MOLECULAR MARKERS IMPROVES PROGNOSTIC STRATIFICATION IN HIGH RISK ENDOMETRIAL CANCER: A TRANSPORTEC COLLABORATIVE STUDY

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Pulmonary Hypertension in the Context of Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure and frequently is associated with pulmonary hypertension (PH). HFpEF associated with PH may be difficult to distinguish from precapillary forms of PH, although this distinction is crucial because therapeutic pathways are divergent for the two conditions. A comprehensive and systematic approach using history, clinical examination, and noninvasive and invasive evaluation with and without provocative testing may be necessary for accurate diagnosis and phenotyping. After diagnosis, HFpEF associated with PH can be subdivided into isolated postcapillary pulmonary hypertension (IpcPH) and combined postcapillary and precapillary pulmonary hypertension (CpcPH) based on the presence or absence of elevated pulmonary vascular resistance. CpcPH portends a worse prognosis than IpcPH. Despite its association with reduced functional capacity and quality of life, heart failure hospitalizations, and higher mortality, therapeutic options focused on PH for HFpEF associated with PH remain limited. In this review, we aim to provide an updated overview on clinical definitions and hemodynamically characterized phenotypes of PH, pathophysiologic features, therapeutic strategies, and ongoing challenges in this patient population.SCOPUS: re.jinfo:eu-repo/semantics/publishe

A Peierls Transition in Long Polymethine Molecular Wires:Evolution of Molecular Geometry and Single-Molecule Conductance

Molecules capable of mediating charge transport over several nanometers with minimal decay in conductance have fundamental and technological implications. Polymethine cyanine dyes are fascinating molecular wires because up to a critical length, they have no bond-length alternation (BLA) and their electronic structure resembles a one-dimensional free-electron gas. Beyond this threshold, they undergo a symmetry-breaking Peierls transition, which increases the HOMO-LUMO gap. We have investigated cationic cyanines with central polymethine chains of 5-13 carbon atoms (Cy3+-Cy11+). The absorption spectra and crystal structures show that symmetry breaking is sensitive to the polarity of the medium and the size of the counterion. X-ray crystallography reveals that Cy9·PF6 and Cy11·B(C6F5)4 are Peierls distorted, with high BLA at one end of the π-system, away from the partially delocalized positive charge. This pattern of BLA distribution resembles that of solitons in polyacetylene. The single-molecule conductance is essentially independent of molecular length for the polymethine salts of Cy3+-Cy11+ with the large B(C6F5)4- counterion, but with the PF6- counterion, the conductance decreases for the longer molecules, Cy7+-Cy11+, because this smaller anion polarizes the π-system, inducing a symmetry-breaking transition. At higher bias (0.9 V), the conductance of the shorter chains, Cy3+-Cy7+, increases with length (negative attenuation factor, β = -1.6 nm-1), but the conductance still drops in Cy9+ and Cy11+ with the small polarizing PF6- counteranion