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This article describes the experience of the Care Delivery Network as it promoted the successful diffusion of an innovative stroke treatment protocol across a wide range of healthcare institutions and practitioners in southeastern Ontario, Canada. The article is founded on research by Adler, Kwon, and Signer on knowledge management in professional communities. The Care Delivery Network case provides partial to strong empirical support for 17 Adler et al. research propositions. The article concludes with a summary of lessons learned and strategies for information and knowledge dissemination in professional settings.

In Canada, as throughout most of the geopolitical West, honour crimes have recently been the object of growing hostility from politicians and media pundits. In many ways, the projection of a \"civilized\" Canada simultaneously reifies the notion of Islamic and/or \"Eastern \" law as inherently contrary, even antithetical, to Canadian law. Yet honour is no foreign notion to Western law, including Canadian law. In this article, we outline how socio-legal hybridity manifests itself in the notion of honour in law, and sketch a definition and history of honour crimes, a category which existed in the West and often travelled to the East. Then, we explore the (Western) \"provocation defence,\" an institution which is historically rooted in male honour and whose concrete operation in Canada has sometimes been to uphold homicidal schemes that are no stranger to notions of bruised honour. We aim to outline that honour is found intertwined with many other emotions in violent crimes in both the \"East\" and the \"West.\" [PUBLICATION ABSTRACT]

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.Competing Interest StatementR.B., J.K. and M.H.D are listed as inventors of a patent describing the drug combinations discovered here. R.B. is a member of the board of directors of Lixte Biotechnology. R.B and M.H.D. are shareholders of Lixte Biotechnology. J.K. is employee of Lixte and shareholder in the company. This work was supported in part by a research grant for Lixte Biotechnology. A.V. and A.Vil. are co-founders of Xenopat S.L.

\"2 The theme around which all the stellar cast of contributors rally could be summed up aptly in the turn of phrase that surfaces just once in the first few pages of the fascinating contribution from Professor Werner Menski: \"navigating diversities,\" a lesson Professor Menski compellingly urges us to learn through the historical and continuing example of India.3 After the editors' two introductory chapters, which provide the theoretical background on cultural diversity, accommodation, and how global balances of power influence the \"irreversible social fact\" of minority populations,4 Professor Menski embarks on a detailed study of how India's legal system has taken a \"historically grounded, sophisticated approach to such questions of uniformity and diversity . . . so much more readily than Britain or other European countries, in order to account for difference. On the one hand, the former observation regarding the role of secularism is nowhere more apparent than in the chapters that touch on European examples, such as in the contributions that examine recent decades in France by Martine Cohen and Claire de Galembert.12 Two contributors, Claire de Galembert and Samantha Knights, specifically discuss the interpretation and application of Article 9 of the European Convention for the Protection of Human Rights and Fundamental Freedoms, which provides a right to freedom of thought, conscience, and religion.13 This provision became central in the widely discussed cases of Muslim girls' and women's right to wear a veil in public places.

Childhood abuse is a major public health problem that has been linked to depression in adulthood. Although different types of childhood abuse often co-occur, few studies have examined their unique impact on negative mental health outcomes. Most studies have focused solely on the consequences of childhood physical or sexual abuse; however, it has been suggested that childhood emotional abuse is more strongly related to depression. It remains unclear which underlying psychological processes mediate the effect of childhood emotional abuse on depressive symptoms. In a cross-sectional study in 276 female college students, multiple linear regression analyses were used to determine whether childhood emotional abuse, physical abuse, and sexual abuse were independently associated with depressive symptoms, emotion dysregulation, and interpersonal problems. Subsequently, OLS regression analyses were used to determine whether emotion dysregulation and interpersonal problems mediate the relationship between childhood emotional abuse and depressive symptoms. Of all types of abuse, only emotional abuse was independently associated with depressive symptoms, emotion dysregulation, and interpersonal problems. The effect of childhood emotional abuse on depressive symptoms was mediated by emotion dysregulation and the following domains of interpersonal problems: cold/distant and domineering/controlling. The results of the current study indicate that detection and prevention of childhood emotional abuse deserves attention from Child Protective Services. Finally, interventions that target emotion regulation skills and interpersonal skills may be beneficial in prevention of depression.

Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5–20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells. A broad application of liposomes calls for high throughout techniques to produce them in a controlled and fast manner. Here, Deshpande et al . show a microfluidic approach using alcohol-based lipid-carrying material to generate monodisperse and unilamellar liposomes within a just few minutes.

The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader range of locations, including housekeeping closets, wastewater from hospital internal pipes, and external manholes. We compared these data with previously collected information from 5 years of patient clinical and surveillance isolates. Whole-genome sequencing and analysis of 108 isolates provided comprehensive characterization of bla KPC / bla NDM -positive isolates, enabling an in-depth genetic comparison. Strikingly, despite a very low prevalence of patient infections with bla KPC -positive organisms, all samples from the intensive care unit pipe wastewater and external manholes contained carbapenemase-producing organisms (CPOs), suggesting a vast, resilient reservoir. We observed a diverse set of species and plasmids, and we noted species and susceptibility profile differences between environmental and patient populations of CPOs. However, there were plasmid backbones common to both populations, highlighting a potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes. Clear associations between patient and environmental isolates were uncommon based on sequence analysis and epidemiology, suggesting reasonable infection control compliance at our institution. Nonetheless, a probable nosocomial transmission of Leclercia sp. from the housekeeping environment to a patient was detected by this extensive surveillance. These data and analyses further our understanding of CPOs in the hospital environment and are broadly relevant to the design of infection control strategies in many infrastructure settings. IMPORTANCE Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections. A 5-year genomic and epidemiological survey was undertaken to study the CPOs in the patient-accessible environment, as well as in the plumbing system removed from the patient. This comprehensive survey revealed a vast, unappreciated reservoir of CPOs in wastewater, which was in contrast to the low positivity rate in both the patient population and the patient-accessible environment. While there were few patient-environmental isolate associations, there were plasmid backbones common to both populations. These results are relevant to all hospitals for which CPO colonization may not yet be defined through extensive surveillance. Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections. A 5-year genomic and epidemiological survey was undertaken to study the CPOs in the patient-accessible environment, as well as in the plumbing system removed from the patient. This comprehensive survey revealed a vast, unappreciated reservoir of CPOs in wastewater, which was in contrast to the low positivity rate in both the patient population and the patient-accessible environment. While there were few patient-environmental isolate associations, there were plasmid backbones common to both populations. These results are relevant to all hospitals for which CPO colonization may not yet be defined through extensive surveillance.

Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults. Participants were randomized to BtB + depression treatment as usual (BTB + TAU, = 81) or TAU ( = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling. Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, = 0.089, 95% confidence interval [CI] 0.85-9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month ( = -4.00, = 0.009, 95% CI -6.97 to -1.02, = 0.27) and 6-month follow-up ( = -3.20, = 0.032, 95% CI -6.13 to -0.27, = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month ( = -0.57, = 0.732, 95% CI -3.83 to 2.69) nor after 6-month follow-up ( = -0.44, = 0.793, 95% CI -3.69 to 2.82). The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use. Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).

Previous studies have suggested that living kidney donors maintain long-term renal function and experience no increase in cardiovascular or all-cause mortality. However, most analyses have included control groups less healthy than the living donor population and have had relatively short follow-up periods. Here we compared long-term renal function and cardiovascular and all-cause mortality in living kidney donors compared with a control group of individuals who would have been eligible for donation. All-cause mortality, cardiovascular mortality, and end-stage renal disease (ESRD) was identified in 1901 individuals who donated a kidney during 1963 through 2007 with a median follow-up of 15.1 years. A control group of 32,621 potentially eligible kidney donors was selected, with a median follow-up of 24.9 years. Hazard ratio for all-cause death was significantly increased to 1.30 (95% confidence interval 1.11–1.52) for donors compared with controls. There was a significant corresponding increase in cardiovascular death to 1.40 (1.03–1.91), while the risk of ESRD was greatly and significantly increased to 11.38 (4.37–29.6). The overall incidence of ESRD among donors was 302 cases per million and might have been influenced by hereditary factors. Immunological renal disease was the cause of ESRD in the donors. Thus, kidney donors are at increased long-term risk for ESRD, cardiovascular, and all-cause mortality compared with a control group of non-donors who would have been eligible for donation.

We introduce a framework of cascading tipping, i.e. a sequence of abrupt transitions occurring because a transition in one subsystem changes the background conditions for another subsystem. A mathematical framework of elementary deterministic cascading tipping points in autonomous dynamical systems is presented containing the double-fold, fold–Hopf, Hopf–fold and double-Hopf as the most generic cases. Statistical indicators which can be used as early warning indicators of cascading tipping events in stochastic, non-stationary systems are suggested. The concept of cascading tipping is illustrated through a conceptual model of the coupled North Atlantic Ocean – El Niño–Southern Oscillation (ENSO) system, demonstrating the possibility of such cascading events in the climate system.