Developing a Presumptive Test for Select Synthetic Cannabinoids

Synthetic cannabinoids (SC\u27s) began to gain popularity around the world in 2009. Since then, many of the compounds have been outlawed and methods developed to detect them and their metabolites using mass spectrometry. Our work investigated the possibility of developing a colorimetric presumptive test. The SC JWH-019 was synthesized and its ketone targeted as a possible reaction site. Many SC\u27s contain ketones and thus a reaction at this site would be applicable to many of the compounds. Since JWH-019 is costly and time consuming to synthesize, much of the experimental work was done using benzophenone (BP). BP contains a diaryl ketone making it comparable to JWH-019. Our initial work studied existing presumptive tests, one for SC\u27s and one for cannabis. Both gave negative results for JWH-019. From there, we looked at synthesizing imines that might be colored. We studied reactions using dinitrophenylhydrazone, hydrazine, aniline and neutral red. Through these reactions it became apparent that the ketones on BP and JWH-019 were reluctant to react. Finally, we studied forming imines of BP with either ethylenediamine (en) or semicarbazide. The resulting product was then used to produce a metal complex. A complex formed between the en-BP product and Cu2+ provided a change in color, but the en-BP imine proved difficult to obtain and the results were not consistent

An Enhanced Mentoring Model’s Impact on Youth in Boys and Girls Clubs

Although federal funding has been provided to add mentoring to youth development programs for decades, we still lack knowledge about the impacts of mentoring on youth outcomes. This research seeks to fill a gap by documenting youth outcomes from an enhanced mentoring approach for urban Boys and Girls Clubs (BGC) in the Southeastern United States delivered by paid staff who serve as mentors through group activities and 1:1 interactions with youth. We perform logistic regressions of secondary data from a cohort of BGCs to understand the relationships between enhanced mentoring and youth outcomes related to program retention, behaviors, and academics. We find the presented approach has a significant relationship with retention with those mentored being 1.92 times more likely to return the following program year. Mentored youth also experienced higher expectations from staff and were less likely to be involved in a physical fight with peers

Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer

BACKGROUND: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide high probability to identify the genetic predisposition for each family. METHODS: In this study, we tested genetic predispositions by analyzing the family-specific variants in familial breast cancer. Using exome sequencing, we analyzed three families and 22 probands with BRCAx (BRCA-negative) familial breast cancer. RESULTS: We observed the presence of family-specific, novel, deleterious germline variants in each family. Of the germline variants identified, many were shared between the disease-affected family members of the same family but not found in different families, which have their own specific variants. Certain variants are putative deleterious genetic predispositions damaging functionally important genes involved in DNA replication and damaging repair, tumor suppression, signal transduction, and phosphorylation. CONCLUSIONS: Our study demonstrates that the predispositions for many BRCAx familial breast cancer families can lie in each disease family. The application of a family-focused approach has the potential to detect many new predispositions

Direct Evidence for Termination of Obscured Star Formation by Radiatively Driven Outflows in Reddened QSOs

We present optical to far-infrared photometry of 31 reddened QSOs that show evidence for radiatively driven outflows originating from AGN in their rest-frame UV spectra. We use these data to study the relationships between the AGN-driven outflows, and the AGN and starburst infrared luminosities. We find that FeLoBAL QSOs are invariably IR-luminous, with IR luminosities exceeding 10^{12} Solar luminosities in all cases. The AGN supplies 76% of the total IR emission, on average, but with a range from 20% to 100%. We find no evidence that the absolute luminosity of obscured star formation is affected by the AGN-driven outflows. Conversely, we find an anticorrelation between the strength of AGN-driven outflows, as measured from the range of outflow velocities over which absorption exceeds a minimal threshold, and the contribution from star formation to the total IR luminosity, with a much higher chance of seeing a starburst contribution in excess of 25% in systems with weak outflows than in systems with strong outflows. Moreover, we find no convincing evidence that this effect is driven by the IR luminosity of the AGN. We conclude that radiatively driven outflows from AGN can have a dramatic, negative impact on luminous star formation in their host galaxies. We find that such outflows act to curtail star formation such that star formation contributes less than ~25% of the total IR luminosity. We also propose that the degree to which termination of star formation takes place is not deducible from the IR luminosity of the AGN.Comment: Accepted for publication in Ap

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Lynch Syndrome-Associated Extracolonic Tumors Are Rare in Two Extended Families With the Same EPCAM Deletion

The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some families were found to show a LS phenotype without an identified MMR mutation, although there was microsatellite instability and absence of MSH2 expression by immunohistochemistry. Studies of a subset of these families found a deletion at the 3′ end of the epithelial cell adhesion molecule (EPCAM) gene, causing transcription read-through resulting in silencing of MSH2 through hypermethylation of its promoter. The tumor spectrum of such families appears to differ from classical LS

Spatial Modulation of Primate Inferotemporal Responses by Eye Position

Background: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information. Methodology/Principal Findings: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40 % of recorded neurons with small gaze angle shifts from central fixation. Although eye position modulates responses, it does not change shape selectivity. Conclusions/Significance: These data demonstrate that spatial information is available in AIT for the representation of objects and scenes within a non-retinocentric frame of reference. More generally, the availability of spatial information in AIT calls into questions the classic dichotomy in visual processing that associates object shape processing with ventra

Perspectives on ethnic and racial disparities in Alzheimer\u27s disease and related dementias: Update and areas of immediate need

Alzheimer\u27s disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer\u27s Association International Society to Advance Alzheimer\u27s Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise “state-of-the-science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations. © 2018 The Author