Drug-Induced Homicide: Challenges and Strategies in Criminal Defense

Nearing the end of its second decade, the crisis of fatal opioid-involved overdoses in the United States has gone from bad to worse. In 2017, approximately 72,000 people died of a drug overdose in the United States. Overdose is now the leading cause of death for people under fifty. There is broad agreement that reducing opioid overdose deaths requires wider distribution of the opioid antidote naloxone, rapid scale-up in evidence-based treatment, and reducing the stigma associated with substance use and addiction. However, progress on these and other vital public health interventions remains abysmally slow. Meanwhile, there is a new and growing trend in enforcing drug-induced homicide and similar laws in overdose death cases. Originally intended to implicate dealers in accidental drug overdoses, such charges were rarely brought until recent years. Just since 2010, however, media coverage of prosecutions based on such provisions has spiked at least threefold, from 363 in 2011 to 1,178 in 2016

Cardiothoracic CT: one-stop-shop procedure? Impact on the management of acute pulmonary embolism

In the treatment of pulmonary embolism (PE) two groups of patients are traditionally identified, namely the hemodynamically stable and instable groups. However, in the large group of normotensive patients with PE, there seems to be a subgroup of patients with an increased risk of an adverse outcome, which might benefit from more aggressive therapy than the current standard therapy with anticoagulants. Risk stratification is a commonly used method to define subgroups of patients with either a high or low risk of an adverse outcome. In this review the clinical parameters and biomarkers of myocardial injury and right ventricular dysfunction (RVD) that have been suggested to play an important role in the risk stratification of PE are described first. Secondly, the use of more direct imaging techniques like echocardiography and CT in the assessment of RVD are discussed, followed by a brief outline of new imaging techniques. Finally, two risk stratification models are proposed, combining the markers of RVD with cardiac biomarkers of ischemia to define whether patients should be admitted to the intensive care unit (ICU) and/or be given thrombolysis, admitted to the medical ward, or be safely treated at home with anticoagulant therapy

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Tissue and host species-specific transcriptional changes in models of experimental visceral leishmaniasis [version 2; referees : 4 approved]

Background: Human visceral leishmaniasis, caused by infection with Leishmania donovani or L. infantum, is a potentially fatal disease affecting 50,000-90,000 people yearly in 75 disease endemic countries, with more than 20,000 deaths reported. Experimental models of infection play a major role in understanding parasite biology, host-pathogen interaction, disease pathogenesis, and parasite transmission. In addition, they have an essential role in the identification and pre-clinical evaluation of new drugs and vaccines. However, our understanding of these models remains fragmentary. Although the immune response to Leishmania donovani infection in mice has been extensively characterized, transcriptomic analysis capturing the tissue-specific evolution of disease has yet to be reported. Methods: We provide an analysis of the transcriptome of spleen, liver and peripheral blood of BALB/c mice infected with L. donovani. Where possible, we compare our data in murine experimental visceral leishmaniasis with transcriptomic data in the public domain obtained from the study of L. donovani-infected hamsters and patients with human visceral leishmaniasis. Digitised whole slide images showing the histopathology in spleen and liver are made available via a dedicated website, www.leishpathnet.org. Results: Our analysis confirms marked tissue-specific alterations in the transcriptome of infected mice over time and identifies previously unrecognized parallels and differences between murine, hamster and human responses to infection. We show commonality of interferon-regulated genes whilst confirming a greater activation of type 2 immune pathways in infected hamsters compared to mice. Cytokine genes and genes encoding immune checkpoints were markedly tissue specific and dynamic in their expression, and pathways focused on non-immune cells reflected tissue specific immunopathology. Our data also addresses the value of measuring peripheral blood transcriptomics as a potential window into underlying systemic disease. Conclusions: Our transcriptomic data, coupled with histopathologic analysis of the tissue response, provide an additional resource to underpin future mechanistic studies and to guide clinical research

Partial-post Laplace barriers for virtual confinement, stable displacement, and &gt;5 cm s(-1) electrowetting transport.

Laplace barriers composed of full-posts or ridges have been previously reported as a mechanism for virtual fluid confinement, but with unstable displacement (capillary fingering or fluid trapping, respectively). A new platform of 'partial-posts' eliminates the disadvantages of full-posts or ridges, while providing ~60-80% open channel area for rapid electrowetting fluid transport (&gt;5 cm s(-1)). The fluid mechanics of partial-post Laplace barriers are far more complex than previous Laplace barriers as it involves two mechanisms: fluid can first begin to propagate either between, or under, the partial-posts. Careful design of channel and partial-post geometries is required, else one mechanism will dominate over the other. The physics and performance of partial-post Laplace barriers are verified using theoretical equations, experimental results, and dynamic numerical modeling

Erratum: Partial-post Laplace barriers for virtual confinement, stable displacement, and &gt;5 cm s-1 electrowetting transport (Lab on a Chip - Miniaturisation for Chemistry and Biology (2011) 11 (4221-4227) DOI: 10.1039/c1lc20749k)

info:eu-repo/semantics/publishe

Partial-post Laplace barriers for virtual confinement, stable displacement, and >5 cm s(-1) electrowetting transport.

Laplace barriers composed of full-posts or ridges have been previously reported as a mechanism for virtual fluid confinement, but with unstable displacement (capillary fingering or fluid trapping, respectively). A new platform of 'partial-posts' eliminates the disadvantages of full-posts or ridges, while providing ~60-80% open channel area for rapid electrowetting fluid transport (>5 cm s(-1)). The fluid mechanics of partial-post Laplace barriers are far more complex than previous Laplace barriers as it involves two mechanisms: fluid can first begin to propagate either between, or under, the partial-posts. Careful design of channel and partial-post geometries is required, else one mechanism will dominate over the other. The physics and performance of partial-post Laplace barriers are verified using theoretical equations, experimental results, and dynamic numerical modeling.Journal Articleinfo:eu-repo/semantics/publishe

Scaling Dielectrowetting Optical Shutters to Higher Resolution: Microfluidic and Optical Implications

A detailed study is reported on the implications of scaling dielectrowetting optical shutters to higher resolutions. Reducing droplet sizes from millimeters to 100 μm in diameter increases the relevance of microfluidic physics such as pinning, film breakup, and dewetting speed as well as optical physics such as transmission and diffraction. In addition, in this work we present improved material systems, including optimized dielectric stacks which reduce electrochemical degradation, and blended lower-viscosity fluids which increase dewetting speed. A higher-resolution device of ∼250 μm diameter demonstrates switching speeds of <100 ms and a clear, optically transmissive aperture of >70%. In addition to revealing science not previously discussed, this work has strong applied importance as scaling to higher resolutions is desirable for improving visual appearance in applications ranging from smart windows to electronic signage