University of Utah

About: University of Utah is a education organization based out in Salt Lake City, Utah, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 52894 authors who have published 124076 publications receiving 5265834 citations. The organization is also known as: The U & The University of Utah.

Importance and vulnerability of the world's water towers

Abstract: Mountains are the water towers of the world, supplying a substantial part of both natural and anthropogenic water demands1,2. They are highly sensitive and prone to climate change3,4, yet their importance and vulnerability have not been quantified at the global scale. Here we present a global water tower index (WTI), which ranks all water towers in terms of their water-supplying role and the downstream dependence of ecosystems and society. For each water tower, we assess its vulnerability related to water stress, governance, hydropolitical tension and future climatic and socio-economic changes. We conclude that the most important (highest WTI) water towers are also among the most vulnerable, and that climatic and socio-economic changes will affect them profoundly. This could negatively impact 1.9 billion people living in (0.3 billion) or directly downstream of (1.6 billion) mountainous areas. Immediate action is required to safeguard the future of the world’s most important and vulnerable water towers.

Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia

Abstract: BACKGROUND Irreversible inhibition of Bruton’s tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors. METHODS In this uncontrolled, phase 1–2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion. RESULTS The median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. At a median followup of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis; the remaining 5% of patients had stable disease. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter’s transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred. CONCLUSIONS In this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. (Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443.)

A developmental-contextual model of couples coping with chronic illness across the adult life span.

Abstract: A developmental-contextual model of couples coping with chronic illness is presented that views chronic illness as affecting the adjustment of both the patient and the spouse such that coping strategies enacted by the patient are examined in relation to those enacted by the spouse, and vice versa. The developmental model emphasizes that dyadic coping may be different at various phases of the life span, changing temporally at different stages of dealing with the illness as well as unfolding daily as spouses interact around dyadic stressors. In addition, couples engaged in dyadic coping are affected by broad sociocultural factors (culture and gender) as well as more proximal contextual factors (quality of the marital relationship and the specific demands of the chronic illness). The model provides a framework for understanding how couples coping with chronic illness may together appraise and cope with illness during adulthood and for determining when spousal involvement is beneficial or harmful to both patient and spousal adjustment. The developmental-contextual model to dyadic appraisal and coping has numerous research implications for the field, and the authors conclude with specific recommendations for future research.

Assessing Alternative Proxies for the Expected Risk Premium

Abstract: Managers, investors, and researchers have a compelling interest in identifying a reliable empirical proxy for firm‐specific cost of equity capital (r). In theory, deducing r is possible if the market's future cash flow forecast and current stock price are observable. Practically, deducing r is dependent on the ability to estimate the market's forecasted terminal value. We evaluate five methods of deducing firm‐specific r (labeled rDIVPREM, rGLSPREM, rGORPREM, rOJNPREM, and rPEGPREM) that deal with this conundrum differently. The extent to which the estimates are associated with firm risk in a stable and meaningful manner is the basis for our assessment. We find that the rDIVPREM and rPEGPREM estimates are consistently and predictably related to risk, while the alternatives are not. Based on these results, we conclude that rDIVPREM and rPEGPREM dominate the alternatives.