The Importance of Core Labor Rights in World Development

This Article discusses the meaning and significance of core labor standards and the importance of linking them to trade agreements. It explains why the protectionist label often attributed to such linkage efforts by their detractors is misleading, as the example of China illustrates, repression of labor rights constitutes a form of unfair competition which undermines efforts to create a more just and stable world economy

Reprogramming human T cell function and specificity with non-viral genome targeting.

Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells

Language of Lullabies: The Russification and De-Russification of the Baltic States

This article argues that the laws for promotion of the national languages are a legitimate means for the Baltic states to establish their cultural independence from Russia and the former Soviet Union

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

The Importance of Core Labor Rights in World Development

This Article discusses the meaning and significance of core labor standards and the importance of linking them to trade agreements. It explains why the protectionist label often attributed to such linkage efforts by their detractors is misleading, as the example of China illustrates, repression of labor rights constitutes a form of unfair competition which undermines efforts to create a more just and stable world economy

Self-care moderates the relationship between symptoms and health-related quality of life in heart failure

Background: Physical symptoms and depression in heart failure (HF) are key drivers of health-related quality of life (HRQOL). Heart failure self-care behaviors are believed to influence how symptoms affect HRQOL. Objective: The goal of this study was to determine if HF self-care behaviors moderate the relationships between physical and depressive symptoms and HRQOL. Methods: In a cohort of adults with moderate to advanced HF, multivariate linear regression was used to evaluate the interaction between self-care behaviors (Self-care of HF index maintenance and management scales) and physical HF symptoms (HF Somatic Perception Scale) on emotional HRQOL (emotional dimension of Minnesota Living With HF Questionnaire). The interaction between self-care behaviors and depression (9-item Patient Health Questionnaire) was evaluated on physical HRQOL (physical dimension of Minnesota Living With HF Questionnaire). Results: The mean age of the sample (N = 202) was 57 ± 13 years, 50% were women, and 61% had New York Heart Association class III or IV HF. Controlling for age, Seattle HF score, functional ability, and comorbidities, self-care maintenance and management moderated the relationship between physical HF symptoms and emotional HRQOL. Only self-care maintenance moderated the relationship between depression and physical HRQOL. Conclusion: In HF, HRQOL is dependent on both the severity of physical and depressive symptoms and the level of engagement in HF self-care behaviors. Future research should consider both self-care behaviors and symptoms when examining patient HRQOL

Self-care Moderates the Relationship Between Symptoms and Health-Related Quality of Life in Heart Failure

Background: Physical symptoms and depression in heart failure (HF) are key drivers of health-related quality of life (HRQOL). Heart failure self-care behaviors are believed to influence how symptoms affect HRQOL. Objective: The goal of this study was to determine if HF self-care behaviors moderate the relationships between physical and depressive symptoms and HRQOL. Methods: In a cohort of adults with moderate to advanced HF, multivariate linear regression was used to evaluate the interaction between self-care behaviors (Self-care of HF index maintenance and management scales) and physical HF symptoms (HF Somatic Perception Scale) on emotional HRQOL (emotional dimension of Minnesota Living With HF Questionnaire). The interaction between self-care behaviors and depression (9-item Patient Health Questionnaire) was evaluated on physical HRQOL (physical dimension of Minnesota Living With HF Questionnaire). Results: The mean age of the sample (N = 202) was 57 ± 13 years, 50% were women, and 61% had New York Heart Association class III or IV HF. Controlling for age, Seattle HF score, functional ability, and comorbidities, self-care maintenance and management moderated the relationship between physical HF symptoms and emotional HRQOL. Only self-care maintenance moderated the relationship between depression and physical HRQOL. Conclusion: In HF, HRQOL is dependent on both the severity of physical and depressive symptoms and the level of engagement in HF self-care behaviors. Future research should consider both self-care behaviors and symptoms when examining patient HRQOL

Device-detected congestion is associated with worse patient-reported outcomes in heart failure

Background Congestion is a common cause of symptoms in heart failure (HF). Yet, intrathoracic impedance, an objective marker of cardiopulmonary congestion, has not been examined in relation to HF symptoms. Objective To determine whether device-detected cardiopulmonary congestion is a predictor of physical and psychological symptoms and health-related quality of life (HRQOL) in adults with HF over 3 months. Methods Multivariate generalized linear modeling was used to quantify the association of cardiopulmonary congestion (Optivol® Index exceeding 60 Ω threshold) with HRQOL (12-item Kansas City Cardiomyopathy Questionnaire) and both physical symptoms (Functional Assessment of Chronic Illness Therapy-Fatigue Scale; HF Somatic Perception Scale Dyspnea and Early & Subtle Symptoms subscales) and affective symptoms (9-item Patient Health Questionnaire; 6-item Patient-Reported Outcomes Measurement Information System Anxiety Scale). Results The mean age of the sample (n = 49) was 62years old, 39% were women, and 63% had NYHA class III/IV HF. Participants who experienced threshold crossings in the previous 90days reported on average, 130% higher dyspnea (p = 0.017; confidence interval (CI) 10.2%, 437%), 40% higher early & subtle symptoms (p = 0.029; CI 3.4%, 89.7%), 106% higher depressive symptoms (p = 0.003; CI 19.1%, 257%) and 40% higher anxiety (p = 0.028; CI 3.7%, 89.1%). Threshold crossings in the previous 90days were also significantly associated with a clinically meaningful decrease in HRQOL (β = −16.16 ± 6.32; p = 0.01). Conclusions Intrathoracic impedance measured with the Optivol Index can provide additional information regarding the patient experience of hallmark physical and psychological HF symptoms and HRQOL over 3months