Systematic Analysis of Priority Water Resources Problems to Develop a Comprehensive Research Program for the Southern Plains River Basins Region

During the past twenty years, there have been several evaluations of national water resources research requirements. Many states have made similar analyses of their water resources research needs. Funding for water resources research generally has not been directed to these identified requirements; also, the level of funding has not been commensurated with the magnitude of the water resources problems. The Office of Water Research and Technology and the associated state water resources research institutes (or centers) initiated a regional problem analysis program to improve the effectiveness of research programs on major regional and national water resources problems. Today no single university or water resource agency possesses the competence to adequately analyze our major water resources problems and to conduct the research necessary to solve these problems, thus the regional problem analysis program was conducted in close cooperation between the universities and the state and federal water resource agencies in the region. The state institutes (or centers) in the Southern Plains River Basins Region Joined together and developed a series of workshops to analyze some of the major regional water resources problems. The water resources research institutes in the Southern Plains River Basins Region have made significant contributions to water resources knowledge in their respective states. In spite of this, the Institutes are striving to improve the effectiveness of their research programs. A potential area for improving the effectiveness of the Institutes is through the inter-institute cooperative problem analysis program to identify research needs for urgent regional water resources problems. This approach provides an opportunity to examine the "total" problem, all alternative solutions, and the probable impact of research on solution of these problems. Upon completion of the systematic analysis of these problems, the Institutes should be able to provide more effective leadership in the state water resources research programs. The objectives of the systematic problem analysis program for the region was as follows: 1. To develop a detailed description of each regional priority problem and sub-problems. 2. To identify and describe the alternatives and sub-alternatives of each priority problem and sub-problems. 3. To identify and describe the knowledge essential to implementation of the complete alternatives sets. 4. To develop a comprehensive research program for the Southern Plains River Basins Region based on the research needs and feasible alternatives identified in the systematic analysis. The objectives at the problem analysis program was accomplished through a series of workshops. Prior to the workshops, considerable discussion was held in each state on important water resource problems. The water resources research institute directors in each state had input on the problem from state and federal agencies in each state as well as faculty knowledge in the area of the particular problem. Thus, the institute directors had input into the problem analysis process from the water resources profession on each problem and sub-problems being conducted by the region

In search of stool donors: a multicentre study of prior knowledge, perceptions, motivators and deterrents among potential donors for fecal microbiota transplantation

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention

Changes in Hepatic Gene Expression upon Oral Administration of Taurine-Conjugated Ursodeoxycholic Acid in ob/ob Mice

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with considerable morbidities. Unfortunately, there is no currently available drug established to treat NAFLD. It was recently reported that intraperitoneal administration of taurine-conjugated ursodeoxycholic acid (TUDCA) improved hepatic steatosis in ob/ob mice. We hereby examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice. Compared to the control ob/ob mice, TUDCA treated ob/ob mice revealed markedly reduced liver fat stained by oil red O (44.2±5.8% vs. 21.1±10.4%, P<0.05), whereas there was no difference in body weight, oral glucose tolerance, insulin sensitivity, and ER stress. Microarray analysis of hepatic gene expression demonstrated that oral TUDCA treatment mainly decreased the expression of genes involved in de novo lipogenesis among the components of lipid homeostasis. At pathway levels, oral TUDCA altered the genes regulating amino acid, carbohydrate, and drug metabolism in addition to lipid metabolism. In summary, oral TUDCA treatment decreased hepatic steatosis in ob/ob mice by cooperative regulation of multiple metabolic pathways, particularly by reducing the expression of genes known to regulate de novo lipogenesis

Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation

Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. In a prospective cohort of allogeneic HCT recipients who received letermovir, we compared polyfunctional CMV-specific T-cell responses to those of controls who received PCR-guided preemptive therapy before the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at 3 months after HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen-specific T-cell subsets. Use of letermovir and reduction of viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjustment for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8(+) responses to pp65, whereas the CMV shedding rate was associated with greater CD4(+) responses to IE-1. In summary, our study provided initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly related to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality may identify patients at risk for late CMV infection after HCT