Focusing on optic tectum circuitry through the lens of genetics

The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain

Nature with a Human Touch: Human-Induced Alteration Negatively Impacts Perceived Naturalness and Preferences for Natural Environments

Natural environments vary in the degree to which humans have altered them; some environments, like wilderness areas, are relatively untouched, while others, like urban green spaces, are heavily manicured. The current research examined the effect of human-induced alteration to natural environments on perceived naturalness and environmental preferences in a student sample (Study 1) and a sample of nonstudent adults (Study 2). It was predicted that a human-altered natural environment would be viewed as less natural than a non-altered natural environment. It was also predicted that a human-altered natural environment would be viewed more negatively than a non-altered natural environment. Results largely supported these predictions. Human-altered natural environments were viewed as less natural than non-altered natural environments, and across several indicators of environmental preference, participants responded more negatively to human-altered natural environments than non-altered natural environments. Perceived naturalness mediated the effect of human-induced alteration on each environmental preference variable, suggesting that non-altered environments are preferred because they are viewed as more natural than their human-altered counterparts. These findings are consistent with an evolutionary account of non-altered natural environments offering more benefits and entailing fewer costs than human-altered natural environments. (PsycINFO Database Record (c) 2016 APA, all rights reserved) (journal abstract

Signal Intensity Analysis and Optimization for in Vivo Imaging of Cherenkov and Excited Luminescence.

During external beam radiotherapy (EBRT), in vivo Cherenkov optical emissions can be used as a dosimetry tool or to excite luminescence, termed Cherenkov-excited luminescence (CEL) with microsecond-level time-gated cameras. The goal of this work was to develop a complete theoretical foundation for the detectable signal strength, in order to provide guidance on optimization of the limits of detection and how to optimize near real time imaging. The key parameters affecting photon production, propagation and detection were considered and experimental validation with both tissue phantoms and a murine model are shown. Both the theoretical analysis and experimental data indicate that the detection level is near a single photon-per-pixel for the detection geometry and frame rates commonly used, with the strongest factor being the signal decrease with the square of distance from tissue to camera. Experimental data demonstrates how the SNR improves with increasing integration time, but only up to the point where the dominance of camera read noise is overcome by stray photon noise that cannot be suppressed. For the current camera in a fixed geometry, the signal to background ratio limits the detection of light signals, and the observed in vivo Cherenkov emission is on the order of 100×  stronger than CEL signals. As a result, imaging signals from depths  \u3c 15 mm is reasonable for Cherenkov light, and depths  \u3c 3 mm is reasonable for CEL imaging. The current investigation modeled Cherenkov and CEL imaging of two oxygen sensing phosphorescent compounds, but the modularity of the code allows for easy comparison of different agents or alternative cameras, geometries or tissues

Identification of a novel germline SPOP mutation in a family with hereditary prostate cancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106871/1/pros22818.pd

Development, Calibration, and Validation of a U.S. White Male Population-Based Simulation Model of Esophageal Adenocarcinoma

The incidence of esophageal adenocarcinoma (EAC) has risen rapidly in the U.S. and western world. The aim of the study was to begin the investigation of this rapid rise by developing, calibrating, and validating a mathematical disease simulation model of EAC using available epidemiologic data.The model represents the natural history of EAC, including the essential biologic health states from normal mucosa to detected cancer. Progression rates between health states were estimated via calibration, which identified distinct parameter sets producing model outputs that fit epidemiologic data; specifically, the prevalence of pre-cancerous lesions and EAC cancer incidence from the published literature and Surveillance, Epidemiology, and End Results (SEER) data. As an illustrative example of a clinical and policy application, the calibrated and validated model retrospectively analyzed the potential benefit of an aspirin chemoprevention program.Model outcomes approximated calibration targets; results of the model's fit and validation are presented. Approximately 7,000 cases of EAC could have been prevented over a 30-year period if all white males started aspirin chemoprevention at age 40 in 1965.The model serves as the foundation for future analyses to determine a cost-effective screening and management strategy to prevent EAC morbidity and mortality

Mitigating alemtuzumab-associated autoimmunity in MS: A whack-a-mole B-cell depletion strategy

Objective: To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity. Methods: In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m2), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy. Results: Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed. Conclusions: An anti-CD20 whack-a-mole B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation. Classification of evidence: This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases

Syndemic factors associated with adult sexual HIV risk behaviors in a sample of Latino men who have sex with men in New York City

Objective: Syndemic theory has been proposed as a framework for understanding the role of multiple riskfactors driving the HIV epidemic among sexual and gender minority individuals. As yet, the frameworkhas been relatively absent in research on Latinos/as.Methods: We used logistic regression to assess relationships among cumulative syndemic conditions –including clinically significant depression, high-risk alcohol consumption, discrimination, and childhoodsexual abuse – engagement with multiple partners and condomless anal intercourse (CAI) in a sample of176 Latino men who have sex with men (MSM) in New York City.Results: In bivariate analyses, an increase in the number of syndemic factors experienced was associatedwith an increased likelihood of reporting multiple partners and CAI. In multivariable analyses, participantswith 2, 3, and 4 factors were significantly more likely to report multiple partners than those with 0(aOR = 4.66, 95% CI [1.29, 16.85); aOR = 7.28, 95% CI [1.94, 27.28] and aOR = 8.25, 95% CI [1.74, 39.24]respectively; p \u3c 0.05. Regarding CAI, only participants with 3 and 4 factors differed from those with 0aOR = 7.35, 95% CI [1.64, 32.83] and OR = 8.06, 95% CI [1.39, 46.73] respectively.Conclusions: Comprehensive approaches that address syndemic factors, and capitalize on resiliency, areneeded to address the sexual health needs of Latino MSM

Syndemic factors associated with adult sexual HIV risk behaviors in a sample of Latino men who have sex with men in New York City

Objective: Syndemic theory has been proposed as a framework for understanding the role of multiple riskfactors driving the HIV epidemic among sexual and gender minority individuals. As yet, the frameworkhas been relatively absent in research on Latinos/as.Methods: We used logistic regression to assess relationships among cumulative syndemic conditions –including clinically significant depression, high-risk alcohol consumption, discrimination, and childhoodsexual abuse – engagement with multiple partners and condomless anal intercourse (CAI) in a sample of176 Latino men who have sex with men (MSM) in New York City.Results: In bivariate analyses, an increase in the number of syndemic factors experienced was associatedwith an increased likelihood of reporting multiple partners and CAI. In multivariable analyses, participantswith 2, 3, and 4 factors were significantly more likely to report multiple partners than those with 0(aOR = 4.66, 95% CI [1.29, 16.85); aOR = 7.28, 95% CI [1.94, 27.28] and aOR = 8.25, 95% CI [1.74, 39.24]respectively; p \u3c 0.05. Regarding CAI, only participants with 3 and 4 factors differed from those with 0aOR = 7.35, 95% CI [1.64, 32.83] and OR = 8.06, 95% CI [1.39, 46.73] respectively.Conclusions: Comprehensive approaches that address syndemic factors, and capitalize on resiliency, areneeded to address the sexual health needs of Latino MSM

Assessing Daylight & Low-Dose Rate Photodynamic Therapy Efficacy, Using Biomarkers of Photophysical, Biochemical and Biological Damage Metrics in Situ.

Background Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused by conventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure. Methods Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, and STAT3 cross-linking from Western blot analysis. Light sources compared included a low fluence rate red LED panel, compact fluorescent bulbs, halogen bulbs and direct sunlight, as compared to traditional PDT delivery with conventional and fractionated high fluence rate red LED light delivery. Results Of the three biomarkers, two had strong correlation to the PpIX-weighted light dose, which is calculated as the product of the treatment light dose (J/cm2) and the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX-weighted light dose had an R = 0.74, and comparison of keratinocyte nuclear damage R = 0.70. There was little correlation to PpIX fluorescence. These assays indicate most of the low fluence rate treatment modalities were as effective as conventional PDT, while fractionated PDT showed the most damage. Conclusions Daylight or artificial light PDT provides an alternative schedule for delivery of drug-light treatment, and this pre-clinical assay demonstrated that in vivo assays of damage could be used to objectively predict a clinical outcome in this altered delivery process. Graphical abstract Low-fluence daylight photodynamic therapy (PDT) has been shown to reduce pain with similar efficacy of conventional treatments. Three objective assays were performed to assess efficacy of different light treatment strategies: PpIX photobleaching, STAT3 crosslinking, and keratinocyte damage. Of these metrics, STAT3 crosslinking and keratinocyte damage showed a strong correlation to the PpIX-weighted light dose

Feasibility study for a microwave-powered ozone sniffer aircraft

The preliminary design of a high-altitude, remotely-piloted, atmospheric-sampling aircraft powered by microwave energy beamed from ground-based antenna was completed. The vehicle has a gross weight of 6720 pounds and is sized to carry a 1000 pound payload at an altitude of 100,000 feet. The underside of the wing serves as the surface of a rectenna designed to receive microwave energy at a power density of 700 watts per square meter and the wing has a planform area of 3634 square feet to absorb the required power at an optimum Mach number M = 0.44. The aircraft utilizes a horizontal tail and a canard for longitudinal control and to enhance the structural rigidity of the twin fuselage configuration. The wing structure is designed to withstand a gust-induced load factor n = 3 at cruise altitude but the low-wing loading of the aircraft makes it very sensitive to gusts at low altitudes, which may induce load factors in excess of 20. A structural load alleviation system is therefore proposed to limit actual loads to the designed structural limit. Losses will require transmitted power on the order of megawatts to be radiated to the aircraft from the ground station, presenting environmental problems. Since the transmitting antenna would have a diameter of several hundred feet, it would not be readily transportable, so we propose that a single antenna be constructed at a site from which the aircraft is flown. The aircraft would be towed aloft to an initial altitude at which the microwave power would be utilized. The aircraft would climb to cruise altitude in a spiral flight path and orbit the transmitter in a gentle turn