Response Rates for Mail Surveys of Nonprofit Organizations: A Review and Empirical Test

The failure of a substantial portion of mail survey recipients to respond to invitations to participate in research projects raises issues of nonresponse error. Because this error is difficult to quantify, survey researchers seek high rates of return to signal legitimacy and reduce questions regarding nonresponse bias. Research on survey method indicates that the design of the survey research process has a measurable influence on the rate of survey returns. This article focuses on three aspects of research design that are expected to influence mail survey returns in surveys of nonprofit organizations: questionnaire complexity, use of Federal Express versus standard mail, and the use of monetary incentives. Using an experimental design, the research concludes that questionnaire complexity and the use of monetary incentives generate no difference in returns, whereas the use of Federal Express to deliver the survey to nonprofit executives has a measurable positive effect

Gα12 Activation in Podocytes Leads to Cumulative Changes in Glomerular Collagen Expression, Proteinuria and Glomerulosclerosis

Glomerulosclerosis is a common pathologic finding that often progresses to renal failure. The mechanisms of chronic kidney disease progression are not well-defined but may include activation of numerous vasoactive and inflammatory pathways. We hypothesized that podocytes are susceptible to filtered plasma components including hormones and growth factors that stimulate signaling pathways leading to glomerulosclerosis. Gα12 couples to numerous G-protein-coupled receptors (GPCR) and regulates multiple epithelial responses including proliferation, apoptosis, permeability and the actin cytoskeleton. Herein, we report that genetic activation of Gα12 in podocytes leads to time dependent increases in proteinuria and glomerulosclerosis. To mimic activation of Gα12-pathways, constitutively active Gα12(QL) was conditionally expressed in podocytes using Nphs2-Cre and LacZfloxed QLα12 transgenic mice. Some QLα12$^{LacZ+/Cre+}$ mice developed proteinuria at 4-6m, and most were proteinuric by 12m. Proteinuria increased with age, and by 12-14m many demonstrated glomerulosclerosis with ultrastructural changes including foot process fusion and both mesangial and subendothelial deposits. QLα12$^{LacZ+/Cre+}$ mice showed no changes in podocyte number, apoptosis, proliferation, or Rho/Src activation. Real-time PCR revealed no significant changes in Nphs1, Nphs2, Cd2ap, or Trpc6 expression, but Col4a2 message was increased in younger and older mice while Col4a5 was decreased in older mice. Confocal microscopy revealed disordered collagen IVα1/2 staining in older mice and loss of α5 without changes in other collagen IV subunits. Taken together, these studies suggest that Gα12 activation promotes glomerular injury without podocyte depletion through a novel mechanism regulating collagen (α)IV expression, and supports the notion that glomerular damage may accrue through persistent GPCR activation in podocytes

Swiss Survey on current practices and opinions on clinical constellations triggering the search for PNH clones.

UNLABELLED This national survey investigated the current practice in Switzerland by collecting participants' opinions on paroxysmal nocturnal hemoglobinuria (PNH) clone assessment and clinical practice. AIM This study aimed to investigate clinical indications prompting PNH clones' assessment and physician's accessibility of a flow cytometry facility, and also to understand clinical attitudes on the follow-up (FU) of patients with PNH clones. METHODS The survey includes 16 multiple-choice questions related to PNH and targets physicians with a definite level of experience in the topic using two screener questions. Opinion on clinical management was collected using hypothetical clinical situations. Each participant had the option of being contacted to further discuss the survey results. This was an online survey, and 264 physicians were contacted through email once a week for 5 weeks from September 2020. RESULTS In total, 64 physicians (24.2%) from 23 institutions participated (81.3% hematologists and 67.2% from university hospitals). All had access to flow cytometry for PNH clone testing, with 76.6% having access within their own institution. The main reasons to assess for PNH clones were unexplained thrombosis and/or hemolysis, and/or aplastic anemia (AA). Patients in FU for PNH clones were more likely to be aplastic anemia (AA) and symptomatic PNH. In total, 61% of the participants investigated PNH clones repetitively during FU in AA/myelodysplastic syndromes patients, even when there was no PNH clone found at diagnosis, and 75% of the participants tested at least once a year during FU. Opinions related to clinical management were scattered. CONCLUSION The need to adhere to guidelines for the assessment, interpretation, and reporting of PNH clones emerges as the most important finding, as well as consensus for the management of less well-defined clinical situations. Even though there are several international guidelines, clear information addressing specific topics such as the type of anticoagulant to use and its duration, as well as the indication for treatment with complement inhibitors in some borderline situations are needed. The analysis and the discussion of this survey provide the basis for understanding the unmet needs of PNH clone assessment and clinical practice in Switzerland

Defining causality in COVID-19 and neurological disorders.

When faced with acute neurological presentations in a patient with COVID-19, how confident can one be that SARS-CoV2 is causal

Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms

Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin’s PC growth inhibition in the context of a prediabetic state is unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. In DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic tumor growth and mTOR-related signaling. The rapamycin effects centered on decreased mTOR-regulated growth and survival signaling, including increased expression of let-7b and cell cycle–regulating miRs. Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail. Metformin also reduced the number and size of Panc02 tumor spheres in vitro and inhibited the expression of Notch in spheroids. Our results suggest that metformin and rapamycin can both inhibit pancreatic tumor growth in obese, prediabetic mice through shared and distinct mechanisms. Metformin and direct mTOR inhibitors, alone or possibly in combination, represent promising intervention strategies for breaking the diabetes-PC link

Evaluation of the Parasight Platform for Malaria Diagnosis

The World Health Organization estimates that nearly 500 million malaria tests are performed annually. While microscopy and rapid diagnostic tests (RDTs) are the main diagnostic approaches, no single method is inexpensive, rapid, and highly accurate. Two recent studies from our group have demonstrated a prototype computer vision platform that meets those needs. Here we present the results from two clinical studies on the commercially available version of this technology, the Sight Diagnostics Parasight platform, which provides malaria diagnosis, species identification, and parasite quantification. We conducted a multisite trial in Chennai, India (Apollo Hospital [n = 205]), and Nairobi, Kenya (Aga Khan University Hospital [n = 263]), in which we compared the device to microscopy, RDTs, and PCR. For identification of malaria, the device performed similarly well in both contexts (sensitivity of 99% and specificity of 100% at the Indian site and sensitivity of 99.3% and specificity of 98.9% at the Kenyan site, compared to PCR). For species identification, the device correctly identified 100% of samples with Plasmodium vivax and 100% of samples with Plasmodium falciparum in India and 100% of samples with P. vivax and 96.1% of samples with P. falciparum in Kenya, compared to PCR. Lastly, comparisons of the device parasite counts with those of trained microscopists produced average Pearson correlation coefficients of 0.84 at the Indian site and 0.85 at the Kenyan site

Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism

Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.)Glenn Foundation for Medical ResearchNational Institutes of Health (U.S.) (Grant 5-P50-090381-09)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Burroughs Wellcome FundSmith Family FoundationDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.) (Grant 1R01DK075850-01)National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

Smoking cessation support by text message during pregnancy: a qualitative study of views and experiences of the MiQuit intervention

Introduction: SMS text messaging is increasingly used for delivering smoking cessation support and pilot studies suggest this may also be useful in pregnancy. This study explores the views of women who received a tailored text messaging cessation intervention (MiQuit) during pregnancy, focusing on acceptability, perceived impact, and suggestions for improvements. Methods: Semi-structured interviews were undertaken with 15 purposively sampled women who had received the MiQuit intervention during pregnancy as part of a randomized controlled trial. Data were analyzed thematically. Results: Three main themes were identified: “impact”, “approach,” and “optimization.” Participants described an immediate, yet often short-lived, impact from the texts that distracted and delayed them from smoking and they perceived that texts focusing on the development of and risk to the baby generated more enduring emotional impacts. Most women found receiving support by text preferable to face-to-face cessation support, with participants citing the greater regularity, convenience, and non-judgmental style as particular advantages. Participants would have preferred a longer support program with increased tailoring, greater customization of text timings and consideration of cutting down as an alternative/precursor to quitting. Conclusion: Pregnancy-specific cessation support by text message was well received and participants considered the support increased their motivation to stop smoking. The focus on the developing baby, the regularity of contact and the provision of gentle, encouraging messages were highlighted as particularly important elements of the program. Implications: This study adds further evidence to the acceptability and perceived positive impact of text-messaging programs in aiding smoking cessation in pregnancy. The findings indicate that for some women, this type of support is preferable to face-to-face methods and could be utilized by health professionals, either in addition to current methods or as an alternative. This study is also relevant to researchers developing health-related text programs to consider participants’ desire for greater tailoring. Further research is required into adapting and continuing text support for women postpartum

Metformin improves healthspan and lifespan in mice

Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced LDL and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging