Delectatio and Recreational Drug Use: Using Aquinas' Account of Pleasure to Argue That Recreational Drug Use Is Immoral.

This article offers a new argument for why recreational drug use is inherently immoral. Typical arguments against recreational drug use focus on legality, purposefully undermining the ability to reason, and harmful health effects. This argument recovers St.

Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis.

The aim of this study was to evaluate the effect of intraoperative botulinum toxin (BT) injection on delayed gastric emptying (DGE) and need for endoscopic pyloric intervention (NEPI) following esophagectomy. In compliance with Preferred Reporting Items for Systematic reviews and Meta-Analyses statement standards, a systematic review of studies reporting the outcomes of intraoperative BT injection in patients undergoing esophagectomy for esophageal cancer was conducted. Proportion meta-analysis model was constructed to quantify the risk of the outcomes and direct comparison meta-analysis model was constructed to compare the outcomes between BT injection and no BT injection or surgical pyloroplasty.

Model selection for assessing the effects of doxorubicin on triple-negative breast cancer cell lines.

Doxorubicin is a chemotherapy widely used to treat several types of cancer, including triple-negative breast cancer. In this work, we use a Bayesian framework to rigorously assess the ability of ten different mathematical models to describe the dynamics of four TNBC cell lines (SUM-149PT, MDA-MB-231, MDA-MB-453, and MDA-MB-468) in response to treatment with doxorubicin at concentrations ranging from 10 to 2500 nM. Each cell line was plated and serially imaged via fluorescence microscopy for 30 days following 6, 12, or 24 h of in vitro drug exposure.

A time-resolved experimental-mathematical model for predicting the response of glioma cells to single-dose radiation therapy.

Purpose: To develop and validate a mechanism-based, mathematical model that characterizes 9L and C6 glioma cells' temporal response to single-dose radiation therapy in vitro by explicitly incorporating time-dependent biological interactions with radiation.

Methods: We employed time-resolved microscopy to track the confluence of 9L and C6 glioma cells receiving radiation doses of 0, 2, 4, 6, 8, 10, 12, 14 or 16 Gy. DNA repair kinetics are measured by γH2AX expression via flow cytometry.

Validation and estimation of spleen volume via computer-assisted segmentation on clinically acquired CT scans.

Deep learning is a promising technique for spleen segmentation. Our study aims to validate the reproducibility of deep learning-based spleen volume estimation by performing spleen segmentation on clinically acquired computed tomography (CT) scans from patients with myeloproliferative neoplasms. As approved by the institutional review board, we obtained 138 de-identified abdominal CT scans.

Experimentally-driven mathematical modeling to improve combination targeted and cytotoxic therapy for HER2+ breast cancer.

The goal of this study is to experimentally and computationally investigate combination trastuzumab-paclitaxel therapies and identify potential synergistic effects due to sequencing of the therapies with in vitro imaging and mathematical modeling. Longitudinal alterations in cell confluence are reported for an in vitro model of BT474 HER2+ breast cancer cells following various dosages and timings of paclitaxel and trastuzumab combination regimens. Results of combination drug regimens are evaluated for drug interaction relationships based on order, timing, and quantity of dose of the drugs.

Cancer mortality rates among US and foreign-born individuals: United States 2005-2014.

From 1970 to 2010 the foreign-born population in the United States has rapidly increased from 9.6 to 40.0 million individuals.

Leveraging Mathematical Modeling to Quantify Pharmacokinetic and Pharmacodynamic Pathways: Equivalent Dose Metric.

Treatment response assays are often summarized by sigmoidal functions comparing cell survival at a single timepoint to applied drug concentration. This approach has a limited biophysical basis, thereby reducing the biological insight gained from such analysis. In particular, drug pharmacokinetic and pharmacodynamic (PK/PD) properties are overlooked in developing treatment response assays, and the accompanying summary statistics conflate these processes.

Cervical Cancer Death Rates Among U.S.- and Foreign-Born Women: U.S., 2005-2014.

Introduction: Historically, foreign-born women in the U.S. are less likely to be screened and are more likely to die from cervical cancer when compared with their U.

Gastric cancer mortality rates among US and foreign-born persons: United States 2005-2014.

Background: Historically, foreign-born individuals in the US have had an elevated risk of dying from gastric cancer when compared to US-born individuals. This is primarily due to factors that occur prior to their immigration to the US, including diet and underlying risk of H. pylori infection.

Mechanism-Based Modeling of Tumor Growth and Treatment Response Constrained by Multiparametric Imaging Data.

Multiparametric imaging is a critical tool in the noninvasive study and assessment of cancer. Imaging methods have evolved over the past several decades to provide quantitative measures of tumor and healthy tissue characteristics related to, for example, cell number, blood volume fraction, blood flow, hypoxia, and metabolism. Mechanistic models of tumor growth also have matured to a point where the incorporation of patient-specific measures could provide clinically relevant predictions of tumor growth and response.

Trends in liver cancer mortality in the United States: Dual burden among foreign- and US-born persons.

Background: Since the mid-1980s, the burden of liver cancer in the United States has doubled, with 31,411 new cases and 24,698 deaths occurring in 2014. Foreign-born individuals may be more likely to die of liver cancer than individuals in the general US-born population because of higher rates of hepatitis B infection, a low socioeconomic position, and language barriers that limit the receipt of early cancer detection and effective treatment.

Methods: To determine whether liver cancer mortality rates were higher among foreign-born individuals versus US-born individuals in the United States, population-based cancer mortality data were obtained from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Mathematical models of tumor cell proliferation: A review of the literature.

A defining hallmark of cancer is aberrant cell proliferation. Efforts to understand the generative properties of cancer cells span all biological scales: from genetic deviations and alterations of metabolic pathways to physical stresses due to overcrowding, as well as the effects of therapeutics and the immune system. While these factors have long been studied in the laboratory, mathematical and computational techniques are being increasingly applied to help understand and forecast tumor growth and treatment response.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC.

Precision Medicine with Imprecise Therapy: Computational Modeling for Chemotherapy in Breast Cancer.

Medical oncology is in need of a mathematical modeling toolkit that can leverage clinically-available measurements to optimize treatment selection and schedules for patients. Just as the therapeutic choice has been optimized to match tumor genetics, the delivery of those therapeutics should be optimized based on patient-specific pharmacokinetic/pharmacodynamic properties. Under the current approach to treatment response planning and assessment, there does not exist an efficient method to consolidate biomarker changes into a holistic understanding of treatment response.

Variable Cell Line Pharmacokinetics Contribute to Non-Linear Treatment Response in Heterogeneous Cell Populations.

We develop a combined experimental-mathematical framework to investigate heterogeneity in the context of breast cancer treated with doxorubicin. We engineer a cell line to over-express the multi-drug resistance 1 protein (MDR1), an ATP-dependent pump that effluxes intracellular drug. Co-culture experiments mixing the MDR1-overexpressing line with its parental line are evaluated via fluorescence microscopy.

A Predictive Mathematical Modeling Approach for the Study of Doxorubicin Treatment in Triple Negative Breast Cancer.

Doxorubicin forms the basis of chemotherapy regimens for several malignancies, including triple negative breast cancer (TNBC). Here, we present a coupled experimental/modeling approach to establish an in vitro pharmacokinetic/pharmacodynamic model to describe how the concentration and duration of doxorubicin therapy shape subsequent cell population dynamics. This work features a series of longitudinal fluorescence microscopy experiments that characterize (1) doxorubicin uptake dynamics in a panel of TNBC cell lines, and (2) cell population response to doxorubicin over 30 days.

Can a Pediatrician Effectively Treat a 9-Year-Old Obese Girl?

Maria is a 9-year-old Latina girl who was followed up by her pediatrician since birth with normal developmental milestones, good school achievement, and without significant medical problems. She was not in the pediatric office for the past 3 years. At the age of 9 years, she presented for a health supervision visit.

Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation.

Background: In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated.

Visual phrase learning and its application in computed tomographic colonography.

In this work, we propose a visual phrase learning scheme to learn an optimal visual composite of anatomical components/parts from CT colonography images for computer-aided detection. The key idea is to utilize the anatomical parts of human body from medical images and associate them with biological targets of interest (organs, cancers, lesions, etc.) for joint detection and recognition.

CDR-restricted engineering of native human scFvs creates highly stable and soluble bifunctional antibodies for subcutaneous delivery.

While myriad molecular formats for bispecific antibodies have been examined to date, the simplest structures are often based on the scFv. Issues with stability and manufacturability in scFv-based bispecific molecules, however, have been a significant hindrance to their development, particularly for high-concentration, stable formulations that allow subcutaneous delivery. Our aim was to generate a tetravalent bispecific molecule targeting two inflammatory mediators for synergistic immune modulation.

CD8+ T-cell activation in HIV-1-infected patients experiencing transient low-level viremia during antiretroviral therapy.

Transient low-level viremia (TLLV) of 50-400 HIV RNA copies per milliliter is common during antiretroviral therapy, but its pathogenesis, consequences, and optimal management are unclear. Heightened immune activation is associated with detrimental outcomes, including impaired CD4 T-cell reconstitution. Using CD38/HLA-DR expression on CD8 T cells measured in 2 large studies, we determined associations between TLLV and immune activation levels before, during, and after TLLV.

Strategies for improved interpretation of computer-aided detections for CT colonography utilizing distributed human intelligence.

Computer-aided detection (CAD) systems have been shown to improve the diagnostic performance of CT colonography (CTC) in the detection of premalignant colorectal polyps. Despite the improvement, the overall system is not optimal. CAD annotations on true lesions are incorrectly dismissed, and false positives are misinterpreted as true polyps.