An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer.

Background: Hepatoblastoma and HCC are the most common malignant hepatocellular tumors seen in children. The aim of this study was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide real-time information about tumor response to therapy.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye used clinically to identify malignant liver cells during surgery.

A novel treatment strategy utilizing panobinostat for high-risk and treatment-refractory hepatoblastoma.

Background & Aims: Patients with metastatic, treatment-refractory, and relapsed hepatoblastoma (HB) have survival rates of less than 50% due to limited treatment options. To develop new therapeutic strategies for these patients, our laboratory has developed a preclinical testing pipeline. Given that histone deacetylase (HDAC) inhibition has been proposed for HB, we hypothesized that we could find an effective combination treatment strategy utilizing HDAC inhibition.

An indocyanine green-based liquid biopsy test for circulating tumor cells for pediatric liver cancer.

Background And Aims: Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common malignant hepatocellular tumors seen in children. The aim of this work was to develop a liquid biopsy test for circulating tumor cells (CTCs) for these tumors that would be less invasive and provide information about the real-time state of tumors in response to therapies.

Methods: For this test, we utilized indocyanine green (ICG), a far-red fluorescent dye that is used clinically to identify malignant liver cells in the body during surgery.

Apixaban for Routine Management of Upper Extremity Deep Venous Thrombosis (ARM-DVT): Methods of a prospective single-arm management study.

Background: Upper extremity deep vein thrombosis (UEDVT) constitutes approximately 10% of all deep vein thromboses (DVTs). The incidence of UEDVT is increasing in association with use of peripherally inserted central venous catheters. Treatment for UEDVT is derived largely from evidence for treatment of lower extremity DVT.

Forward reachable sets: Analytically derived properties of connected components for dynamic networks.

Formal analysis of the emergent structural properties of dynamic networks is largely uncharted territory. We focus here on the properties of forward reachable sets (FRS) as a function of the underlying degree distribution and edge duration. FRS are defined as the set of nodes that can be reached from an initial seed via a path of temporally ordered edges; a natural extension of connected component measures to dynamic networks.

Elementary proof of convergence to the mean-field model for the SIR process.

The susceptible-infected-recovered (SIR) model has been used extensively to model disease spread and other processes. Despite the widespread usage of this ordinary differential equation (ODE) based model which represents the mean-field approximation of the underlying stochastic SIR process on contact networks, only few rigorous approaches exist and these use complex semigroup and martingale techniques to prove that the expected fraction of the susceptible and infected nodes of the stochastic SIR process on a complete graph converges as the number of nodes increases to the solution of the mean-field ODE model. Extending the elementary proof of convergence for the SIS process introduced by Armbruster and Beck (IMA J Appl Math, doi: 10.

A Data-Driven Simulation of HIV Spread Among Young Men Who Have Sex With Men: Role of Age and Race Mixing and STIs.

Objective: Young men who have sex with men (YMSM) in the United States have a high HIV incidence with substantial racial disparities that are poorly understood. We use a data-driven simulation model to understand the impact of network-level mechanisms and sexually transmitted infections on the spread of HIV among YMSM.

Methods: We designed and parameterized a stochastic agent-based network simulation model using results of a longitudinal cohort study of YMSM in Chicago.

Population and dyadic-based seroincidence of herpes simplex virus-2 and syphilis in southern India.

Objectives: Herpes simplex virus-2 (HSV-2) and syphilis are associated with increased risk of HIV, highlighting the importance of understanding their transmission dynamics. In India, most studies of HSV-2 and syphilis incidence are in high-risk populations and may not accurately reflect infectious activity. In this study, we aim to define HSV-2/syphilis incidence and risk factors in a population sample.

Sex role segregation and mixing among men who have sex with men: implications for biomedical HIV prevention interventions.

Objective: Men who have sex with men (MSM) practice role segregation - insertive or receptive only sex positions instead of a versatile role - in several international settings where candidate biomedical HIV prevention interventions (e.g., circumcision, anal microbicide) will be tested.

The importance of extended high viremics in models of HIV spread in South Africa.

Recent studies found a substantial fraction of 'extended high viremics' among HIV-1 subtype C, the most common subtype in southern Africa. Extended high viremics are HIV infected individuals who maintain a high viral load for a longer time period than usual after the initial infection. They are more infectious during this period, and their infection progresses to full-blown AIDS and death much faster than usual.

HIV status awareness, partnership dissolution and HIV transmission in generalized epidemics.

Objectives: HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC) that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV.

The cost-effectiveness of expanded HIV screening in the United States.

Objective: The current Centers of Disease Control and Prevention (CDC) guidelines from 2006 recommend a one-time test for low-risk individuals and annual testing for those at high risk. These guidelines may not be aggressive enough, even for those at low risk of infection, due to the earlier initiation of HAART and a movement towards a test-and-treat environment. We evaluated the optimal testing frequencies for various risk groups in comparison to the CDC recommendations.

Effectiveness of a no-sex or safe-sex month in reducing HIV transmission.

Objective: To build a deterministic compartmental model for exploring the effects on the transmission of human immunodeficiency virus (HIV) of a population abstaining from sex or practising only "safe" sex for one month each year.

Methods: A model of HIV transmission was built to simulate the effects of the intervention (i.e.

Investigations on cytotoxic and genotoxic effects of laser printer emissions in human epithelial A549 lung cells using an air/liquid exposure system.

Exposure to emissions from laser printers during the printing process is commonplace worldwide, both in the home and workplace environment. In the present study, cytotoxic and genotoxic effects of the emission from five low to medium-throughput laser printers were investigated with respect to the release of ozone (O(3) ), volatile organic compounds (VOC), particulate matter (PM), and submicrometer particles (SMP) during standby and operation. Experiments were conducted in a 1 m(3) emission chamber connected to a Vitrocell® exposure system.

Exploring the relative costs of contact tracing for increasing HIV case finding in sub-Saharan countries.

Background: Contact tracing (CT) has rarely been used to improve HIV case finding in sub-Saharan Africa because of concerns regarding privacy protection and possibly high costs.

Methods: We estimate the relative cost of identifying an undiagnosed HIV infection through CT compared with client-initiated voluntary counseling and testing (VCT) and door-to-door provider-initiated testing (PIT). We used data from the Likoma Network Study, a study of sexual networks and HIV infection conducted on the small island of Likoma in northern Malawi, to inform these calculations.

The reliability of sexual partnership histories: implications for the measurement of partnership concurrency during surveys.

Objectives: To measure the reliability of sexual partnership histories collected during survey interviews and to assess the impact of measurement error on survey estimates of partnership concurrency.

Methods: We used sociocentric data collected on Likoma Island (Malawi). Up to five of the respondents' most recent sexual partners were identified in population rosters.

Arachnoid cysts of the middle cranial fossa accompanied by subdural effusions--experience with 60 consecutive cases.

Background: Subdural effusions (SDEs) can complicate arachnoid cysts of the middle cranial fossa (ACMFs). While there is a consensus that at least in adults asymptomatic ACMFs should not be operated, those with concomitant subdural and/or intracystic effusions are clinically apparent in the majority of cases and should be surgically treated. But it remains unclear, which surgical procedure is best.

Cost-effective control of chronic viral diseases: finding the optimal level of screening and contact tracing.

Chronic viral diseases such as human immunodeficiency virus (HIV) and hepatitis B virus (HBV) afflict millions of people worldwide. A key public health challenge in managing such diseases is identifying infected, asymptomatic individuals so that they can receive antiviral treatment. Such treatment can benefit both the treated individual (by improving quality and length of life) and the population as a whole (through reduced transmission).

A chemical-genetic approach to study G protein regulation of beta cell function in vivo.

Impaired functioning of pancreatic beta cells is a key hallmark of type 2 diabetes. beta cell function is modulated by the actions of different classes of heterotrimeric G proteins. The functional consequences of activating specific beta cell G protein signaling pathways in vivo are not well understood at present, primarily due to the fact that beta cell G protein-coupled receptors (GPCRs) are also expressed by many other tissues.

Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors.

Examining the behavioral consequences of selective CNS neuronal activation is a powerful tool for elucidating mammalian brain function in health and disease. Newly developed genetic, pharmacological, and optical tools allow activation of neurons with exquisite spatiotemporal resolution; however, the inaccessibility to light of widely distributed neuronal populations and the invasiveness required for activation by light or infused ligands limit the utility of these methods. To overcome these barriers, we created transgenic mice expressing an evolved G protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug clozapine-N-oxide (CNO).

New insights into the function of M4 muscarinic acetylcholine receptors gained using a novel allosteric modulator and a DREADD (designer receptor exclusively activated by a designer drug).

The M4 muscarinic acetylcholine (ACh) receptor (mAChR) is a potential therapeutic target but characterized by a lack of subtype-selective ligands. We recently generated "designer receptors exclusively activated by a designer drug" (DREADDs), which contained mutations of two conserved orthosteric-site residues (Y113C/A203G in the M4 mAChR) that caused a loss of ACh activity but a gain in responsiveness to clozapine-N-oxide (CNO). The current study characterized the interactions of the wild type and the M4 DREADD with a range of agonists, antagonists, and the recently discovered M4 mAChR allosteric potentiator, 3-amino-5-chloro-6-methoxy-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (LY2033298).