Simulation Models for Suicide Prevention: A Survey of the State-of-the-Art.

Suicide is a leading cause of death and a global public health problem, representing more than one in every 100 deaths in 2019. Modeling and Simulation (M&S) is widely used to address public health problems, and numerous simulation models have investigated the complex, dependent, and dynamic risk factors contributing to suicide. However, no review has been dedicated to these models, which prevents modelers from effectively learning from each other and raises the risk of redundant efforts. To guide the development of future models, in this paper we perform the first scoping review of simulation models for suicide prevention. Examining ten articles, we focus on three practical questions. First, which interventions are supported by previous models? We found that four groups of models collectively support 53 interventions. We examined these interventions through the lens of global recommendations for suicide prevention, highlighting future areas for model development. Second, what are the obstacles preventing model application? We noted the absence of cost effectiveness in all models reviewed, meaning that certain simulated interventions may be infeasible. Moreover, we found that most models do not account for different effects of suicide prevention interventions across demographic groups. Third, how much confidence can we place in the models? We evaluated models according to four best practices for simulation, leading to nuanced findings that, despite their current limitations, the current simulation models are powerful tools for understanding the complexity of suicide and evaluating suicide prevention interventions.

Myosin light chain kinase mediates transcellular intravasation of breast cancer cells through the underlying endothelial cells: a three-dimensional FRET study.

The transient and localized signaling events between invasive breast cancer cells and the underlying endothelial cells have remained poorly characterized. We report a novel approach integrating vascular engineering with three-dimensional time-lapse fluorescence resonance energy transfer (FRET) imaging to dissect how endothelial myosin light chain kinase (MLCK) is modulated during tumor intravasation. We show that tumor transendothelial migration occurs via both paracellular (i.e. through cell-cell junctions) and transcellular (i.e. through individual endothelial cells) routes. Endothelial MLCK is activated at the invasion site, leading to regional diphosphorylation of myosin-II regulatory light chain (RLC) and myosin contraction. Blocking endothelial RLC diphosphorylation blunts tumor transcellular, but not paracellular, invasion. Our results implicate an important role for endothelial myosin-II function in tumor intravasation.

Peripartum Hyperkalemia Caused by Magnesium Infusion in a Woman With End-Stage Renal Disease: A Case Report.

Pregnancy in the setting of renal failure has higher rates of adverse events necessitating increased monitoring and treatment. Pregnant women with end-stage renal disease have higher rates of hypertension, and 50% of pregnancies are complicated by preeclampsia. We describe the case of a 32-year-old parturient with end-stage renal disease on hemodialysis with superimposed preeclampsia who developed clinically significant hyperkalemia with electrocardiographic changes after magnesium infusion. The magnesium infusion was stopped, and the patient underwent emergent hemodialysis with subsequent improvement. Hyperkalemia caused by magnesium infusion is a rare and not very well-understood phenomenon.

Prospective phase II trial of concomitant boost radiotherapy for stage II nasopharyngeal carcinoma: an evaluation of response and toxicity.

INTRODUCTION: Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in loco-regional control of around 80%. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C-Boost) schedule. METHODS AND MATERIALS: Twenty-five 1997 AJCC Stage II NPC patients were enrolled and analyzed in this preliminary report. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. C-Boost for gross disease consisted of 18 Gy in 12 fractions commencing on day 19 and was delivered at least 6 hours after the first dose. Patients were assessed for response, survival, and toxicity. RESULTS: With a median follow-up of 24 months, only one patient had pathologically confirmed local recurrence, necessitating IMRT. Two developed distant metastases for which they received chemotherapy. One died from systemic disease after refusing treatment for persistent neck lymphadenopathy. Two-year loco-regional control rates, overall survival and disease-free survival rates were 96%, 96%, and 88%, respectively. All patients experienced some degree of acute and/or late toxicity. However, the toxicity profile was comparable to that seen following standard fractionation. Acute or late toxicities directly attributable to C-Boost were not observed. CONCLUSION: This C-Boost radiotherapy regimen administers a substantially higher biologically effective dose compared with conventional radiation schedules. Preliminary locoregional control and survival rates are promising with no significant acute and/or late toxicities.