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Sustainable change initiatives are often short-circuited by failures in modelling. Unexamined assumptions about measurement and numbers push modelling into the background as a presupposition rarely articulated as an explicit operation. Even when models of system dynamics are planned components of a sustainable change effort, the key role of measurement is typically overlooked. The crux of the matter concerns the distinction between numeric counts and measured quantities. Mistaking the former for the latter confuses levels of complexity and fundamentally compromises communications. Reconceiving measurement as modelling multilevel distributed decision processes offers new alternatives aligned with historically successful efforts in creating sustainable change. Five conditions for successful sustainable change are contrasted from the perspectives of single-level vs multilevel modelling: vision, plans, skills, resources, and incentives. Omitting any one of these from efforts at creating change result, respectively, in confusion, treadmills, anxiety, frustration, and resistance. The shortcomings of typically implemented single-level approaches to measurement result in the widespread experience of these negative consequences. Results show that new potentials for creating sustainable change can be expected to follow from implementations of multilevel distributed decision processes that effectively counteract organizational amnesia by embedding new learning in an externally materialized knowledge infrastructure incorporating a shared cultural memory.

Global deployment of vaccines poses significant challenges in the distribution and use of the accompanying immunoassays, one of the standard methods for quality control of vaccines, particularly when establishing assays in countries worldwide to support testing/release upon importation. This work describes our effort toward developing an integrated, portable device to carry out affinity assays for viral particles quantification in viral vaccines by incorporating (i) aptamers, (ii) microfluidic devices, and (iii) electrochemical detection. We generated and characterized more than eight aptamers against multiple membrane proteins of cytomegalovirus (CMV), which we used as a model system and designed and fabricated electrochemical microfluidic devices to measure CMV concentrations in a candidate vaccine under development. The aptamer-based assays provided a half maximal effective concentration, EC

Little research has been done to examine the impact of sexual novelty on intimacy, passion, and other relationship quality indicators, despite the lay belief that sexual experimentation can rekindle the lost “spark” in relationships. The current study aimed to fill this gap using a pre-post experimental design embedded within a 29-day dyadic diary framework. After two weeks of providing baseline data concerning feelings of intimacy and passion, ease of sexual communication, and sexual and relationship satisfaction, participating mixed-sex couples (N = 128) were randomly assigned to one of three conditions: a control condition in which couples were not asked to engage in novel sexual activities; a sexual position condition in which couples were asked to try out five novel sexual positions; or a vibrator condition in which couples were asked to use a novel vibrator while engaging in five new sexual positions. Couples then provided assessments of the same relationship quality indicators that had been baselined over the course of two weeks. Passion was significantly higher among participants in the vibrator condition than participants in the control condition immediately following the intervention but declined back to baseline levels by the end of study. No other differences in the relationship quality indicators were found across the conditions. These results suggest that sexual novelty may have short-term effects on passion, though these effects are transitory and unrelated to other aspects of sexual and relationship quality.

Background Blood operators are working to improve donor screening and eligibility for gay, bisexual and other men who have sex with men (gbMSM), and trans and nonbinary donors. Many consider screening all donors for specific sexual risk behaviors to be a more equitable approach that maintains the safety of the blood supply. Feasibility considerations with this change include ensuring donor understanding of additional sexual behavior questions and minimizing donor loss due to discomfort. Study design and methods Qualitative one-on-one interviews were conducted with Canadian whole blood and plasma donors (N = 40). A thematic analysis was conducted to assess participants' understandings of the questions, examine their comfort/discomfort, and identify strategies to mitigate donor discomfort. Results All participants understood what the sexual behavior questions were asking and thought the questions were appropriate. Themes related to comfort/discomfort include: their expectations of donor screening, social norms that they bring to donation, whether their answer felt like personal disclosure, knowing the reasons for the question, trusting confidentiality, confidence in knowing their sexual partner's behavior, and potential for the question to be discriminatory. Strategies to mitigate discomfort include: providing an explanation for the questions, forewarning donors of these questions, reducing ambiguity, and using a self-administered questionnaire. Conclusion While many blood operators and regulators view the move to sexual behavior–based screening for all donors as a significant paradigmatic shift, donors may not perceive additional sexual behavior questions as a significant change to their donation experience. Further research is needed to evaluate the effectiveness of strategies to mitigate donor discomfort.

When there is a predictive biomarker, enrichment can focus the clinical trial on a benefiting subpopulation. We describe a two-stage enrichment design, in which the first stage is designed to efficiently estimate a threshold and the second stage is a "phase III-like" trial on the enriched population. The goal of this paper is to explore design issues: sample size in Stages 1 and 2, and re-estimation of the Stage 2 sample size following Stage 1. By treating these as separate trials, we can gain insight into how the predictive nature of the biomarker specifically impacts the sample size. We also show that failure to adequately estimate the threshold can have disastrous consequences in the second stage. While any bivariate model could be used, we assume a continuous outcome and continuous biomarker, described by a bivariate normal model. The correlation coefficient between the outcome and biomarker is the key to understanding the behavior of the design, both for predictive and prognostic biomarkers. Through a series of simulations we illustrate the impact of model misspecification, consequences of poor threshold estimation, and requisite sample sizes that depend on the predictive nature of the biomarker. Such insight should be helpful in understanding and designing enrichment trials.

An historic shift in focus on the quality and person-centeredness of health care has occurred in the last two decades. Accounts of results produced from reinvigorated attention to the measurement, management, and improvement of the outcomes of health care show that much has been learned, and much remains to be done. This article proposes that causes of the failure to replicate in health care the benefits of “lean” methods lie in persistent inattention to measurement fundamentals. These fundamentals must extend beyond mathematical and technical issues to the social, economic, and political processes involved in constituting trustworthy performance measurement systems. Successful “lean” implementations will follow only when duly diligent investments in these fundamentals are undertaken. Absent those investments, average people will not be able to leverage brilliant processes to produce exceptional outcomes, and we will remain stuck with broken processes in which even brilliant people can produce only flawed results. The methodological shift in policy and practice prescribed by the authors of the chapters in this book moves away from prioritizing the objectivity of data in centrally planned and executed statistical modeling, and toward scientific models that prioritize the objectivity of substantive and invariant unit quantities. The chapters in this book describe scientific modeling’s bottom-up, emergent and evolving standards for mass customized comparability. Though the technical aspects of the scientific modeling perspective are well established in health care outcomes measurement, operationalization of the social, economic, and political aspects required for creating new degrees of trust in health care institutions remains at a nascent stage of development. Potentials for extending everyday thinking in new directions offer hope for achieving previously unattained levels of efficacy in health care improvement efforts.

Purpose Pancreatogenic diabetes refers to diabetes mellitus (DM) that develops in the setting of a disease of the exocrine pancreas, including pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). We sought to evaluate whether a blunted nutrient response of pancreatic polypeptide (PP) can differentiate these DM subtypes from type 2 DM (T2DM). Methods Subjects with new-onset DM ( Results The fasting PP concentration was lower in both the PDAC-DM and CP-DM groups than in the T2DM group (P = 0.03 and Conclusions Fasting PP concentrations and the response to meal stimulation are reduced in new-onset DM associated with PDAC or CP compared with T2DM. These findings support further investigations into the use of PP concentrations to characterize pancreatogenic DM and to understand the pathophysiological role in exocrine pancreatic diseases (NCT03460769).

Although micronutrients modulate immunity and inflammation, it remains elusive whether they are implicated in the development and progression of chronic pancreatitis (CP). This study aimed to investigate differences in the circulating levels of selected carotenoids and vitamins between CP and controls and trends in the levels of these micronutrients across controls, early CP, and definite CP.Demographic and lifestyle data were extracted from medical records for 53 patients with CP (13 early and 38 definite) and obtained using a questionnaire for 52 controls. Plasma β-carotene, lycopene, cryptoxanthin, zeaxanthin, and α-tocopherol and serum 25(OH)D, folate, IL-6, TNF-α, and MCP-1 were measured with state-of-the-art methods.The levels of all micronutrients (except folate) were significantly lower in CP than in controls. There was a progressive decrease in the levels of these micronutrients across controls, early CP, and definite CP (all p values for trend: ≤0.0012); e.g., plasma lycopene was 36.6, 21.5, and 14.5 μg/dL for controls, early CP, and definite CP, respectively. After adjustment for confounders, there were strong, inverse associations between the levels of all micronutrients (except folate) and CP (e.g., OR (95% CI) for ≥ median vs.median: 0.10 (0.04, 0.27) for lycopene, 0.15 (0.05, 0.38) for α-tocopherol, and 0.24 (0.09, 0.64) for 25(OH)D). These associations became weaker after additional adjustment for inflammation markers (IL-6, TNF-α, and MCP-1).The circulating levels of some carotenoids, α-tocopherol, and vitamin D were reduced in CP patients compared with controls and this reduction was more pronounced in definite CP than in early CP.

A Internet das Coisas (IoT) uma cole o em r pida evolu o e expans o de diversas tecnologias que interagem com o mundo f sico. Muitas organiza es n o est o necessariamente cientes do grande n mero de dispositivos IoT que j est o usando e como eles podem afetar a seguran a cibern tica e os riscos de privacidade de diferentes maneiras, comparado aos dispositivos convencionais de tecnologia da informa o (TI). O objetivo desta publica o ajudar as ag ncias federais e outras organiza es a compreender e melhor gerenciar os riscos de seguran a cibern tica e privacidade associados a seus dispositivos IoT individuais durante todo o ciclo de vida de tais dispositivos. Esta publica o um documento introdut rio que serve de base para uma s rie planejada de publica es sobre alguns aspectos mais espec ficos relacionados a este t pico.

La internet de las cosas (IoT) es un conjunto de diversas tecnolog as que evolucionan y se difunden con rapidez, y que interact an con el mundo f sico. Muchas organizaciones no se dan cuenta del gran n mero de dispositivos de IoT que ya est n utilizando, ni de que los dispositivos de IoT pueden afectar a los riesgos a la ciberseguridad y la privacidad de manera distinta de los dispositivos de tecnolog a de la informaci n (TI) convencionales. El objetivo de esta publicaci n es ayudar a los organismos federales y otras organizaciones a conocer y gestionar mejor los riesgos a la ciberseguridad y la privacidad asociados con sus dispositivos individuales de IoT durante el ciclo de vida de estos. Esta publicaci n es un documento introductorio que sirve de base para una serie de publicaciones planificadas sobre aspectos m s espec ficos de este tema.

e16290 Background: The mechanism of human pancreatic ductal adenocarcinoma (PDAC) resistance to nucleoside analog and first-line chemotherapy drug gemcitabine is not clearly understood, but some studies have associated it with increased autophagy. In cancer biology, autophagy plays dual roles as it can promote tumor suppression during early stages, but in established tumors, it plays a crucial role in tumor growth by enhancing survival under metabolic and therapeutic stress. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of a network of tumorigenic factors, including the Valosin-containing protein (VCP), which has been reported to play an important role in autophagy. In this study, we investigate whether the repression of VCP through miR-198 replacement disrupts the autophagy process and sensitizes PDAC cells to gemcitabine treatment. Methods: MIAPaCa2 cells with forced overexpression of mesothelin (MSLN) and AsPC-1 cell lines and, CDX and PDX mouse models were used for gemcitabine sensitization studies. For miR-198 replacement, a miR-198 expression vector-loaded lactic co-glycolic-acid-modified polyethylenimine polyplex (LPNP-p198) was used. Autophagy disruption experiments were run over miR-198 and/or VCP overexpressing cell lines. Nude mice were used for subcutaneous and orthotopic CDX models and SCID/Beige were used for the subcutaneous PDX model. Results: Cell lines were treated with LPNP-p198 in combination with gemcitabine and cell growth was significantly inhibited when compared to gemcitabine alone. Additionally, it was determined that miR-198 disrupts the autophagy maturation process and, that it is then restored by overexpression of VCP. LPNP-p198 can effectively enter tumor cells and induce tumor sensitization in vivo, resulting in an 80-90% reduction of tumor burden and metastatic spread in the LPNP-p198 plus gemcitabine group when compared to controls, with the concomitant downregulation of VCP expression in the tumor tissue. In addition, this group had the fewest mice with jaundice, ascites, and metastases to the abdominal cavity, spleen, liver, and kidney. Finally, to address the potential of the observed effect in the context of the heterogenic nature of PDAC, we confirmed our findings in a PDX mouse model, where a marked reduction in tumor burden was observed in the LPNP-p198 plus gemcitabine group compared to controls. Conclusions: Our findings indicate that miR-198 replacement disrupts the autophagy maturation process and sensitizes PDAC cells to gemcitabine through VCP repression, indicating a potential therapeutic strategy for targeting gemcitabine-resistant PDAC and, establishing the use of LPNPs as a prototype for effective nucleic acid delivery in vitro and in vivo, with potential to be used from bench to clinic.

by Philip E. Nelson, 2007 World Food Prize Laureate; Professor Emeritus, Food Science Dept., Purdue Univ. Just as society has evolved over time, our food system has also evolved over centuries into a global system of immense size and complexity. The commitment of food science and technology professionals to advancing the science of food, ensuring a safe and abundant food supply, and contributing to healthier people everywhere is integral to that evolution. Food scientists and technologists are versatile, interdisciplinary, and collaborative practitioners in a profession at the crossroads of scientific and technological developments. As the food system has drastically changed, from one centered around family food production on individual farms and home food preservation to the modern system of today, most people are not connected to their food nor are they familiar with agricultural production and food manufacturing designed for better food safety and quality. The Institute of Food Technologists-a nonprofit scientific society of individual members engaged in food science, food technology, and related professions in industry, academia, and government-has the mission to advance the science of food and the long-range vision to ensure a safe and abundant food supply contributing to healthier people everywhere. IFT convened a task force and called on contributing authors to develop this scientific review to inform the general public about the importance and benefits of food science and technology in IFT's efforts to feed a growing world. The main objective of this review is to serve as a foundational resource for public outreach and education and to address misperceptions and misinformation about processed foods. The intended audience includes those who desire to know more about the application of science and technology to meet society's food needs and those involved in public education and outreach. It is IFT's hope that the reader will gain a better understanding of the goals or purposes for various applications of science and technology in the food system, and an appreciation for the complexity of the modern food supply. Abstract: This Institute of Food Technologists scientific review describes the scientific and technological achievements that made possible the modern production-to-consumption food system capable of feeding nearly 7 billion people, and it also discusses the promising potential of ongoing technological advancements to enhance the food supply even further and to increase the health and wellness of the growing global population. This review begins with a historical perspective that summarizes the parallel developments of agriculture and food technology, from the beginnings of modern society to the present. A section on food manufacturing explains why food is processed and details various food processing methods that ensure food safety and preserve the quality of products. A section about potential solutions to future challenges briefly discusses ways in which scientists, the food industry, and policy makers are striving to improve the food supply for a healthier population and feed the future. Applications of science and technology within the food system have allowed production of foods in adequate quantities to meet the needs of society, as it has evolved. Today, our production-to-consumption food system is complex, and our food is largely safe, tasty, nutritious, abundant, diverse, convenient, and less costly and more readily accessible than ever before. Scientific and technological advancements must be accelerated and applied in developed and developing nations alike, if we are to feed a growing world population.

Diffuse echogenicity of the pancreas, a commonly discovered finding on endoscopic ultrasound (EUS), is often of undetermined significance. The goal of this study was to characterize the clinical picture and pancreatic function in patients who incidentally present with this endosonographic finding.This was a case-control study comparing consecutive adult patients with diffuse echogenicity of the pancreas found on EUS to those who did not have known pancreas disease. Demographic and clinical data were extracted from the electronic medical record. The primary endpoint was exocrine pancreatic insufficiency (EPI) defined as fecal elastase (FE-1) 200 μg/g.A total of 166 patients were included in this study. There were 89 patients who had diffuse echogenicity of the pancreas on EUS and FE-1 testing. There were 77 control patients with chronic diarrhea who did not have known pancreas disease but did have FE-1 testing. EPI was significantly more likely in the fatty pancreas group compared to the control group (47% vs 6%, p 0.001). There was also a significantly greater proportion of smokers in the fatty pancreas group compared to the control group (42% vs 17%, p = 0.002). There were no other differences in baseline characteristics between the two groups, including prevalence of chronic pancreatitis by Rosemont classification. On multiple logistic regression analysis controlling for multiple variables, smoking (OR 2.26, 95% CI 1.15-4.43) and NAFLD (OR 3.99, 95% CI 1.09-14.70) had significant associations with EPI.This study found a significantly greater amount of patients who had diffuse echogenicity of the pancreas on EUS to also have EPI. This is compared to a control group of patients without known pancreas disease. This prevalence was found in the absence of a significant association with chronic pancreatitis on EUS based on Rosemont classification. Future controlled studies are required to further investigate this relationship.

International audience; Background: Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.Methods: In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin. The primary efficacy outcome of major venous thromboembolism was a composite of symptomatic distal or proximal deep-vein thrombosis, pulmonary embolism, or venous thromboembolism-related death during the treatment period or asymptomatic proximal deep-vein thrombosis at the end of treatment. A test for superiority was planned if rivaroxaban proved to be noninferior to enoxaparin. For all outcomes, multiple imputation was used to account for missing data. Prespecified safety outcomes included major bleeding (fatal, critical, or clinically overt bleeding or bleeding at the surgical site leading to intervention) and nonmajor clinically relevant bleeding.Results: A total of 3604 patients underwent randomization; 1809 patients were assigned to receive rivaroxaban, and 1795 to receive enoxaparin. Major venous thromboembolism occurred in 4 of 1661 patients (0.2%) in the rivaroxaban group and in 18 of 1640 patients (1.1%) in the enoxaparin group (risk ratio with multiple imputation, 0.25; 95% confidence interval, 0.09 to 0.75; P