Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.Toxicolog

Gender Differences in Diabetes Attitudes and Adherence

This study focused on three questions: Is there a difference in men's and women's diabetes attitudes? Do health professionals give different recommendations to men and women? Is there a difference between men and women in care adherence? A total of 1201 patients with diabetes were surveyed; 65% of these patients were women. Differences in diabetes attitudes (three of seven attiticdes) were most evident between men and women with insulin-dependent diabetes mellitus (IDDM). No differences were found in the attitudes of men and women with non-insulin-dependent diabetes mellitus (NIDDM) using insulin, and only one attitude was different for patients with NIDDM not using insulin. Few differences were observed in the recommendations given by health professionals to men and women. Gender differences in adherence to the components of self-care also were minimal. These findings may indicate that there are many similarities in the reactions of men and women who have been diagnosed with diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69143/2/10.1177_014572179502100605.pd

The value of competitive employment:In-depth accounts of people with intellectual disabilities

BackgroundIncreasing the societal participation of people with intellectual disabilities via competitive employment requires a full understanding of what this means to them. This paper aims to provide an in‐depth examination of the lived experiences of people with intellectual disabilities in competitive employment.MethodInterviews were conducted with six participants with mild intellectual disability or borderline functioning and good verbal communication skills. Interviews were analysed according to the guidelines of interpretative phenomenological analysis (IPA). Member checks were conducted.ResultsAnalysis yielded three main themes: (a) Building on my life experiences, (b) My place at work and (c) Being a valuable member of society, like everyone else.ConclusionsCompetitive employment could make a substantial contribution to the sense of belonging to society and quality of life of people with intellectual disabilities. Nevertheless, they must cope with stigma‐related obstacles and feelings of being dependent on others in the work environment

A model of impairment and functional limitation in rheumatoid arthritis

BACKGROUND: We have previously proposed a theoretical model for studying physical disability and other outcomes in rheumatoid arthritis (RA). The purpose of this paper is to test a model of impairment and functional limitation in (RA), using empirical data from a sample of RA patients. We based the model on the disablement process framework. METHODS: We posited two distinct types of impairment in RA: 1) Joint inflammation, measured by the tender, painful and swollen joint counts; and 2) Joint deformity, measured by the deformed joint count. We hypothesized direct paths from the two impairments to functional limitation, measured by the shirt-button speed, grip strength and walking velocity. We used structural equation modeling to test the hypothetical relationships, using empirical data from a sample of RA patients recruited from six rheumatology clinics. RESULTS: The RA sample was comprised of 779 RA patients. In the structural equation model, the joint inflammation impairment displayed a strong significant path toward the measured variables of joint pain, tenderness and swelling (standardized regression coefficients 0.758, 0.872 and 0.512, P ≤ 0.001 for each). The joint deformity impairment likewise displayed significant paths toward the measured upper limb, lower limb, and other deformed joint counts (standardized regression coefficients 0.849, 0.785, 0.308, P ≤ 0.001 for each). Both the joint inflammation and joint deformity impairments displayed strong direct paths toward functional limitation (standardized regression coefficients of -0.576 and -0.564, respectively, P ≤ 0.001 for each), and explained 65% of its variance. Model fit to data was fair to good, as evidenced by a comparative fit index of 0.975, and the root mean square error of approximation = 0.058. CONCLUSION: This evidence supports the occurrence of two distinct impairments in RA, joint inflammation and joint deformity, that together, contribute strongly to functional limitations in this disease. These findings may have implications for investigators aiming to measure outcome in RA

Trends and variation in mild disability and functional limitations among older adults in Norway, 1986–2008

An increase in the number of older adults may raise the demand for health and care services, whereas decreasing prevalence of disability and functional limitations among them might counteract this demographic effect. However, the trends in health are inconsistent between studies and countries. In this article, we estimated the trends in mild disability and functional limitations among older Norwegians and analyzed whether they differ between socio-demographic groups. Data were obtained from repeated cross-sectional surveys conducted in 1987, 1991, 1995, 2002, 2005, and 2008, in total 4,036 non-institutionalized persons aged 67 years or older. We analyzed trends using multivariate logistic regression. On average, the age-adjusted trend in functional limitations was −3.3% per year, and in disability 3.4% per year. The risk for functional limitations or disability was elevated for women compared to men, for married compared to non-married, and was inversely associated with educational level The trends were significantly weaker with increasing age for disabilities, whereas none of the trends differed significantly between subgroups of sexes, educational level or marital status. Both functional limitations free and disability-free life expectancy appeared to have increased more than total life expectancy at age 67 during this period. The analysis suggests downward trends in the prevalence of mild disability and functional limitations among older Norwegians between 1987 and 2008 and a compression of lifetime in such health states. The reduced numbers of older people with disability and functional limitations may have restrained the demand for health and care services caused by the increase in the number of older adults

Gender differences in local and systemic reactions to inactivated influenza vaccine, established by a meta-analysis of fourteen independent studies

In order to determine whether there is a difference between genders in reported adverse reactions to inactivated influenza vaccine, a computerized database of serological studies was investigated. A standardized questionnaire was used to evaluate vaccine reactogenicity. A total of 1,800 vaccinees in 14 studies were analyzed separately for two age groups ( or = 60 years of age). Females reported significantly more local reactions than males. The pooled odds ratio for the outcome measure "any local reaction" was 0.32 (95% confidence interval, 0.26-0.40, significant) and 0.54 (95% Cl, 0.41-0.70, significant) for young and elderly adults, respectively. Similar results were obtained for the outcome measure "any systemic reaction." Previous exposure to influenza or influenza vaccine had no influence on reactogenicity. There were no gender differences in sero-responses. In conclusion, gender should be regarded as a predictor of reported reactions to influenza vaccine in both young and elderly adults and should be addressed in future study designs

The State of the Art in Multilayer Network Visualization

Modelling relationships between entities in real-world systems with a simple graph is a standard approach. However, reality is better embraced as several interdependent subsystems (or layers). Recently the concept of a multilayer network model has emerged from the field of complex systems. This model can be applied to a wide range of real-world datasets. Examples of multilayer networks can be found in the domains of life sciences, sociology, digital humanities and more. Within the domain of graph visualization there are many systems which visualize datasets having many characteristics of multilayer graphs. This report provides a state of the art and a structured analysis of contemporary multilayer network visualization, not only for researchers in visualization, but also for those who aim to visualize multilayer networks in the domain of complex systems, as well as those developing systems across application domains. We have explored the visualization literature to survey visualization techniques suitable for multilayer graph visualization, as well as tools, tasks, and analytic techniques from within application domains. This report also identifies the outstanding challenges for multilayer graph visualization and suggests future research directions for addressing them