Shadows and traces in bicategories

Traces in symmetric monoidal categories are well-known and have many applications; for instance, their functoriality directly implies the Lefschetz fixed point theorem. However, for some applications, such as generalizations of the Lefschetz theorem, one needs "noncommutative" traces, such as the Hattori-Stallings trace for modules over noncommutative rings. In this paper we study a generalization of the symmetric monoidal trace which applies to noncommutative situations; its context is a bicategory equipped with an extra structure called a "shadow." In particular, we prove its functoriality and 2-functoriality, which are essential to its applications in fixed-point theory. Throughout we make use of an appropriate "cylindrical" type of string diagram, which we justify formally in an appendix.Comment: 46 pages; v2: reorganized and shortened, added proof for cylindrical string diagrams; v3: final version, to appear in JHR

Dynamic and physical clustering of gene expression during epidermal barrier formation in differentiating keratinocytes.

The mammalian epidermis is a continually renewing structure that provides the interface between the organism and an innately hostile environment. The keratinocyte is its principal cell. Keratinocyte proteins form a physical epithelial barrier, protect against microbial damage, and prepare immune responses to danger. Epithelial immunity is disordered in many common diseases and disordered epithelial differentiation underlies many cancers. In order to identify the genes that mediate epithelial development we used a tissue model of the skin derived from primary human keratinocytes. We measured global gene expression in triplicate at five times over the ten days that the keratinocytes took to fully differentiate. We identified 1282 gene transcripts that significantly changed during differentiation (false discovery rate <0.01%). We robustly grouped these transcripts by K-means clustering into modules with distinct temporal expression patterns, shared regulatory motifs, and biological functions. We found a striking cluster of late expressed genes that form the structural and innate immune defences of the epithelial barrier. Gene Ontology analyses showed that undifferentiated keratinocytes were characterised by genes for motility and the adaptive immune response. We systematically identified calcium-binding genes, which may operate with the epidermal calcium gradient to control keratinocyte division during skin repair. The results provide multiple novel insights into keratinocyte biology, in particular providing a comprehensive list of known and previously unrecognised major components of the epidermal barrier. The findings provide a reference for subsequent understanding of how the barrier functions in health and disease

The impact of physical, psychological, and sexual intimate partner violence on women's mental health: depressive symptoms, posttraumatic stress disorder, state anxiety, and suicide

Objective: This study aimed to determine the impact of lifetime physical, psychological, and sexual intimate male partner violence (IPV) on the mental health of women, after controlling for the contribution of lifetime victimization. The comorbidity of depressive symptoms and posttraumatic stress disorder (PTSD) and their relation to state anxiety and suicide were also assessed. Methods: Physically/psychologically (n 75) and psychologically abused women (n 55) were compared with nonabused control women (n 52). Information about sociodemographic characteristics, lifetime victimization, and mental health status (depressive and state anxiety symptoms, PTSD, and suicide) was obtained through face-to-face structured interviews. Results: Women exposed to physical/psychological and psychological IPV had a higher incidence and severity of depressive and anxiety symptoms, PTSD, and thoughts of suicide than control women, with no differences between the two abused groups. The concomitance of sexual violence was associated with a higher severity of depressive symptoms in both abused groups and a higher incidence of suicide attempts in the physically/psychologically abused group. The incidence of PTSD alone was very rare, and depressive symptoms were either alone or comorbid with PTSD. The severity of state anxiety was higher in abused women with depressive symptoms or comorbidity, as was the incidence of suicidal thoughts in the physically/psychologically abused group. Lifetime victimization was not a predictor of the deterioration of mental health in this study. Conclusions: These findings indicate that psychological IPV is as detrimental as physical IPV, with the exception of effects on suicidality, which emphasizes that psychological IPV should be considered a major type of violence by all professionals involved.Este es un artículo ampliamente citado internacionalmente respeto a violencia de pareja y consecuencias en la salud de las mujeres

What have we learnt from palaeoclimate simulations?

There has been a gradual evolution in the way that palaeoclimate modelling and palaeoenvironmental data are used together to understand how the Earth System works, from an initial and largely descriptive phase through explicit hypothesis testing to diagnosis of underlying mechanisms. Analyses of past climate states are now regarded as integral to the evaluation of climate models, and have become part of the toolkit used to assess the likely realism of future projections. Palaeoclimate assessment has demonstrated that changes in large-scale features of climate that are governed by the energy and water balance show consistent responses to changes in forcing in different climate states, and these consistent responses are reproduced by climate models. However, state-of-the-art models are still largely unable to reproduce observed changes in climate at a regional scale reliably. While palaeoclimate analyses of state-of-the-art climate models suggest an urgent need for model improvement, much work is also needed on extending and improving palaeoclimate reconstructions and quantifying and reducing both numerical and interpretative uncertainties

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment

Background and purpose An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren’s contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC’s impact on quality of life and the value of its treatments. Methods Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were deined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little ingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0–1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L proile most accurately relects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. Results Estimated utilities based on the responses of 1,745 qualiied respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little ingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little inger from 50 to 12 degrees would improve utility by 0.02. Interpretation DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and lexible framework to assess utility for varying degrees of DC severity

Risk propensity in the foreign direct investment location decision of emerging multinationals

A distinguishing feature of emerging economy multinationals is their apparent tolerance for host country institutional risk. Employing behavioral decision theory and quasi-experimental data, we find that managers’ domestic experience satisfaction increases their relative risk propensity regarding controllable risk (legally protectable loss), but decreases their tendency to accept non-controllable risk (e.g., political instability). In contrast, firms’ potential slack reduces relative risk propensity regarding controllable risk, yet amplifies the tendency to take non-controllable risk. We suggest that these counterbalancing effects might help explain observation that risk-taking in FDI location decisions is influenced by firm experience and context. The study provides a new understanding of why firms exhibit heterogeneous responses to host country risks, and the varying effects of institutions

Accumulation of Endogenous LITAF in Aggresomes

LITAF is a 161 amino acid cellular protein which includes a proline rich N-terminus and a conserved C-terminal domain known as the simple-like domain. Mutations in LITAF have been identified in Charcot-Marie tooth disease, a disease characterized by protein aggregates. Cells transfected with cellular LITAF reveal that LITAF is localized to late endosomes/lysosomes. Here we investigated the intracellular localization of endogenous LITAF. We demonstrated that endogenous LITAF accumulates at a discrete cytoplasmic site in BGMK cells that we identify as the aggresome. To determine the domain within LITAF that is responsible for the localization of LITAF to aggresomes, we created a construct that contained the C-terminal simple-like domain of LITAF and found that this construct also localizes to aggresomes. These data suggest the simple-like domain is responsible for targeting endogenous LITAF to the aggresome

Payments and quality of care in private for-profit and public hospitals in Greece

<p>Abstract</p> <p>Background</p> <p>Empirical evidence on how ownership type affects the quality and cost of medical care is growing, and debate on these topics is ongoing. Despite the fact that the private sector is a major provider of hospital services in Greece, little comparative information on private versus public sector hospitals is available. The aim of the present study was to describe and compare the operation and performance of private for-profit (PFP) and public hospitals in Greece, focusing on differences in nurse staffing rates, average lengths of stay (ALoS), and Social Health Insurance (SHI) payments for hospital care per patient discharged.</p> <p>Methods</p> <p>Five different datasets were prepared and analyzed, two of which were derived from information provided by the National Statistical Service (NSS) of Greece and the other three from data held by the three largest SHI schemes in the country. All data referred to the 3-year period from 2001 to 2003.</p> <p>Results</p> <p>PFP hospitals in Greece are smaller than public hospitals, with lower patient occupancy, and have lower staffing rates of all types of nurses and highly qualified nurses compared with public hospitals. Calculation of ALoS using NSS data yielded mixed results, whereas calculations of ALoS and SHI payments using SHI data gave results clearly favoring the public hospital sector in terms of cost-efficiency; in all years examined, over all specialties and all SHI schemes included in our study, unweighted ALoS and SHI payments for hospital care per discharge were higher for PFP facilities.</p> <p>Conclusions</p> <p>In a mixed healthcare system, such as that in Greece, significant performance differences were observed between PFP and public hospitals. Close monitoring of healthcare provision by hospital ownership type will be essential to permit evidence-based decisions on the future of the public/private mix in terms of healthcare provision.</p

Integrative network analysis identified key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma

Background: Incidence of hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) has been increasing in the United States and Europe during recent years. Although HCV-associated HCC shares many pathological characteristics with other types of HCC, its molecular mechanisms of progression remain elusive. Methods: To investigate the underlying pathology, we developed a systematic approach to identify deregulated biological networks in HCC by integrating gene expression profiles with high-throughput protein-protein interaction data. We examined five stages including normal (control) liver, cirrhotic liver, dysplasia, early HCC and advanced HCC. Results: Among the five consecutive pathological stages, we identified four networks including precancerous networks (Normal-Cirrhosis and Cirrhosis-Dysplasia) and cancerous networks (Dysplasia-Early HCC, Early-Advanced HCC). We found little overlap between precancerous and cancerous networks, opposite to a substantial overlap within precancerous or cancerous networks. We further found that the hub proteins interacted with HCV proteins, suggesting direct interventions of these networks by the virus. The functional annotation of each network demonstrates a high degree of consistency with current knowledge in HCC. By assembling these functions into a module map, we could depict the stepwise biological functions that are deregulated in HCV-induced hepatocarcinogenesis. Additionally, these networks enable us to identify important genes and pathways by developmental stage, such as LCK signalling pathways in cirrhosis, MMP genes and TIMP genes in dysplastic liver, and CDC2-mediated cell cycle signalling in early and advanced HCC. CDC2 (alternative symbol CDK1), a cell cycle regulatory gene, is particularly interesting due to its topological position in temporally deregulated networks. Conclusions: Our study uncovers a temporal spectrum of functional deregulation and prioritizes key genes and pathways in the progression of HCV induced HCC. These findings present a wealth of information for further investigation