Leveraging Epidemiology to Improve Risk Assessment.

The field of environmental public health is at an important crossroad. Our current biomonitoring efforts document widespread exposure to a host of chemicals for which toxicity information is lacking. At the same time, advances in the fields of genomics, proteomics, metabolomics, genetics and epigenetics are yielding volumes of data at a rapid pace. Our ability to detect chemicals in biological and environmental media has far outpaced our ability to interpret their health relevance, and as a result, the environmental risk paradigm, in its current state, is antiquated and ill-equipped to make the best use of these new data. In light of new scientific developments and the pressing need to characterize the public health burdens of chemicals, it is imperative to reinvigorate the use of environmental epidemiology in chemical risk assessment. Two case studies of chemical assessments from the Environmental Protection Agency Integrated Risk Information System database are presented to illustrate opportunities where epidemiologic data could have been used in place of experimental animal data in dose-response assessment, or where different approaches, techniques, or studies could have been employed to better utilize existing epidemiologic evidence. Based on the case studies and what can be learned from recent scientific advances and improved approaches to utilizing human data for dose-response estimation, recommendations are provided for the disciplines of epidemiology and risk assessment for enhancing the role of epidemiologic data in hazard identification and dose-response assessment

Up from Crisis: Overhauling Healthcare Information, Payment, and Delivery in Extraordinary Times. Dialogue with Featured Speakers from the 6th Annual Connected Health Symposium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78098/1/tmj.2009.9948.pd

A Retrospective Study of the Investigation of Homicidal Childhood Asphyxial Deaths

As one of the leading causes of traumatic deaths in newborns, infants, and young children, there is no anatomic or microscopic feature that is pathognomonic for asphyxial deaths. Instead, pathologists rely on investigation information, including confessions and/or witness statements, and potential evidence at the scene. Twenty cases of homicidal newborn, infant, and young children asphyxial deaths were reviewed, which included death and police investigation reports and autopsy reports, as well as histology slides of lung sections. This series of homicidal asphyxial deaths highlight that, in a vast majority of such cases, the final cause and manner of death rulings are dependent on confession by the perpetrator. Furthermore, this series highlights the possible role of histology to help forensic pathologists better certify asphyxial deaths. Finally, this series emphasizes important investigation points and considerations at autopsy during the investigation of asphyxial deaths in newborns, infants, and young children.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144651/1/jfo13666_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144651/2/jfo13666.pd

Oceanographic Structure and Light Levels Drive Patterns of Sound Scattering Layers in a Low-Latitude Oceanic System

Several factors have been reported to structure the spatial and temporal patterns of sound scattering layers, including temperature, oxygen, salinity, light, and physical oceanographic conditions. In this study, we examined the spatiotemporal variability of acoustically detected sound scattering layers in the northern Gulf of Mexico to investigate the drivers of this variability, including mesoscale oceanographic features [e.g., Loop Current-origin water (LCOW), frontal boundaries, and Gulf Common Water]. Results indicate correlations in the vertical position and acoustic backscatter intensity of sound scattering layers with oceanographic conditions and light intensity. LCOW regions displayed consistent decreases, by a factor of two and four, in acoustic backscatter intensity in the upper 200 m relative to frontal boundaries and Gulf Common Water, respectively. Sound scattering layers had greater backscatter intensity at night in comparison to daytime (25x for frontal boundaries, 17x for LCOW, and 12x for Gulf Common Water). The importance of biotic (primary productivity) and abiotic (sea surface temperature, salinity) factors varied across oceanographic conditions and depth intervals, suggesting that the patterns in distribution and behavior of mesopelagic assemblages in low-latitude, oligotrophic ecosystems can be highly dynamic

Generation of Human Striatal Neurons by MicroRNA-Dependent Direct Conversion of Fibroblasts

SummaryThe promise of using reprogrammed human neurons for disease modeling and regenerative medicine relies on the ability to induce patient-derived neurons with high efficiency and subtype specificity. We have previously shown that ectopic expression of brain-enriched microRNAs (miRNAs), miR-9/9∗ and miR-124 (miR-9/9∗-124), promoted direct conversion of human fibroblasts into neurons. Here we show that coexpression of miR-9/9∗-124 with transcription factors enriched in the developing striatum, BCL11B (also known as CTIP2), DLX1, DLX2, and MYT1L, can guide the conversion of human postnatal and adult fibroblasts into an enriched population of neurons analogous to striatal medium spiny neurons (MSNs). When transplanted in the mouse brain, the reprogrammed human cells persisted in situ for over 6 months, exhibited membrane properties equivalent to native MSNs, and extended projections to the anatomical targets of MSNs. These findings highlight the potential of exploiting the synergism between miR-9/9∗-124 and transcription factors to generate specific neuronal subtypes

Diffusing an Innovation: Clinician Perceptions of Continuous Predictive Analytics Monitoring in Intensive Care

Background The purpose of this article is to describe neonatal intensive care unit clinician perceptions of a continuous predictive analytics technology and how those perceptions influenced clinician adoption. Adopting and integrating new technology into care is notoriously slow and difficult; realizing expected gains remain a challenge. Methods Semistructured interviews from a cross-section of neonatal physicians (n ¼ 14) and nurses (n ¼ 8) from a single U.S. medical center were collected 18 months following the conclusion of the predictive monitoring technology randomized control trial. Following qualitative descriptive analysis, innovation attributes from Diffusion of Innovation Theory-guided thematic development. Results Results suggest that the combination of physical location as well as lack of integration into work flow or methods of using data in care decisionmaking may have delayed clinicians from routinely paying attention to the data. Once data were routinely collected, documented, and reported during patient rounds and patient handoffs, clinicians came to view data as another vital sign. Through clinicians’ observation of senior physicians and nurses, and ongoing dialogue about data trends and patient status, clinicians learned how to integrate these data in care decision making (e.g., differential diagnosis) and came to value the technology as beneficial to care delivery. Discussion The use of newly created predictive technologies that provide early warning of illness may require implementation strategies that acknowledge the risk–benefit of treatment cliniciansmust balance and take advantage of existing clinician trainingmethods

Arginine dependence of acute myeloid leukaemia blast proliferation: a novel therapeutic target

Acute myeloid leukemia (AML) is one of the most common acute leukemias in adults and children, yet significant numbers of patients relapse and die of disease. In this study, we identify the dependence of AML blasts on arginine for proliferation. We show that AML blasts constitutively express the arginine transporters CAT-1 and CAT-2B, and that the majority of newly diagnosed patients' blasts have deficiencies in the arginine-recycling pathway enzymes argininosuccinate synthase and ornithine transcarbamylase, making them arginine auxotrophic. BCT-100, a pegylated human recombinant arginase, leads to a rapid depletion in extracellular and intracellular arginine concentrations, resulting in arrest of AML blast proliferation and a reduction in AML engraftment in vivo. BCT-100 as a single agent causes significant death of AML blasts from adults and children, and acts synergistically in combination with cytarabine. Using RNA sequencing, 20 further candidate genes which correlated with resistance have been identified. Thus, AML blasts are dependent on arginine for survival and proliferation, as well as depletion of arginine with BCT-100 of clinical value in the treatment of AML

Perceptions of HIV Risk and Explanations of Sexual Risk Behavior Offered by Heterosexual Black Male Barbershop Patrons in Brooklyn, NY

Objective: To describe HIV risk factors among adult heterosexual Black men recruited from four barbershops located in high HIV seroprevalent neighborhoods of Brooklyn, NY. Methods: Data on HIV-risk related behaviors and other characteristics were collected from barbershop clients. All participants (n=60) completed brief risk assessments; and a subset (n=22) also completed focus groups and/or individual interviews. Results: Of the subset of 22 men, 68% were US born, 59% had been in jail/prison, 32% were unemployed; and during the 3 months before the interviews, 68% reported at least two partners and 45% reported unprotected vaginal or anal sex with two or more women. Emergent themes included: 1) the psychological function of multiple partnerships; 2) calculated risk taking regarding condom use; 3) the role of emotional attachment and partner trust in condom use; 4) low perceived HIV risk and community awareness; and 5) lack of relationship between HIV testing and safer sex practices. Conclusions: Interventions among heterosexual Black men should focus not only on increasing HIV awareness and reducing sexual risk, but also on contextual and interpersonal factors that influence sexual risk

Evaluation of Handheld Assays for the Detection of Ricin and Staphylococcal Enterotoxin B in Disinfected Waters

Development of a rapid field test is needed capable of determining if field supplies of water are safe to drink by the warfighter during a military operation. The present study sought to assess the effectiveness of handheld assays (HHAs) in detecting ricin and Staphylococcal Enterotoxin B (SEB) in water. Performance of HHAs was evaluated in formulated tap water with and without chlorine, reverse osmosis water (RO) with chlorine, and RO with bromine. Each matrix was prepared, spiked with ricin or SEB at multiple concentrations, and then loaded onto HHAs. HHAs were allowed to develop and then read visually. Limits of detection (LOD) were determined for all HHAs in each water type. Both ricin and SEB were detected by HHAs in formulated tap water at or below the suggested health effect levels of 455 ng/mL and 4.55 ng/mL, respectively. However, in brominated or chlorinated waters, LODs for SEB increased to approximately 2,500 ng/mL. LODs for ricin increased in chlorinated water, but still remained below the suggested health effect level. In brominated water, the LOD for ricin increased to approximately 2,500 ng/mL. In conclusion, the HHAs tested were less effective at detecting ricin and SEB in disinfected water, as currently configured

Mitochondrial Hâ‚‚Oâ‚‚ emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans

High dietary fat intake leads to insulin resistance in skeletal muscle, and this represents a major risk factor for type 2 diabetes and cardiovascular disease. Mitochondrial dysfunction and oxidative stress have been implicated in the disease process, but the underlying mechanisms are still unknown. Here we show that in skeletal muscle of both rodents and humans, a diet high in fat increases the Hâ‚‚Oâ‚‚-emitting potential of mitochondria, shifts the cellular redox environment to a more oxidized state, and decreases the redox-buffering capacity in the absence of any change in mitochondrial respiratory function. Furthermore, we show that attenuating mitochondrial Hâ‚‚Oâ‚‚ emission, either by treating rats with a mitochondrial-targeted antioxidant or by genetically engineering the overexpression of catalase in mitochondria of muscle in mice, completely preserves insulin sensitivity despite a high-fat diet. These findings place the etiology of insulin resistance in the context of mitochondrial bioenergetics by demonstrating that mitochondrial Hâ‚‚Oâ‚‚ emission serves as both a gauge of energy balance and a regulator of cellular redox environment, linking intracellular metabolic balance to the control of insulin sensitivity. Original version available at http://www.jci.org/articles/view/3704