Discovery of highly insecticidal synthetic spinosyn mimics – CAMD enabled de novo design simplifying a complex natural product

Simplifying complex natural products: Computer modeling‐based design leads to highly insecticidal, chemically simpler synthetic mimics of the spinosyn natural products that are active in the field

Who the hell was that? Stories, bodies and actions in the world

This article explores a two-way relationship between stories and the experiential actions of bodies in the world. Through an autoethnographic approach, the article presents a series of interlinked story fragments in an effort to show and evoke a feel for the ways in which stories, bodies, and actions influence and shape each other over time. It offers some reflections on the experiences the stories portray from the perspective of a social constructionist conception of narrative theory and suggest that while stories exert a powerful influence on the actions of our bodies, our bodies intrude on or ‘talk back’ to this process because bodies have an existence beyond stories

Evan J. David Correspondence

Entries include typed introductory correspondence from the Maine State Library

Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (<35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

Infrared Properties of High Redshift and X-ray Selected AGN Samples

The NASA/ISO Key Project on active galactic nuclei (AGN) seeks to better understand the broad-band spectral energy distributions (SEDs) of these sources from radio to X-rays, with particular emphasis on infrared properties. The ISO sample includes a wide variety of AGN types and spans a large redshift range. Two subsamples are considered herein: 8 high-redshift (1 < z < 4.7) quasars; and 22 hard X-ray selected sources. The X-ray selected AGN show a wide range of IR continuum shapes, extending to cooler colors than the optical/radio sample of Elvis et al. (1994). Where a far-IR turnover is clearly observed, the slopes are < 2.5 in all but one case so that non-thermal emission remains a possibility. The highest redshift quasars show extremely strong, hot IR continua requiring ~ 100 solar masses of 500 - 1000 Kelvin dust with ~ 100 times weaker optical emission. Possible explanations for these unusual properties include: reflection of the optical light from material above/below a torus; strong obscuration of the optical continuum; or an intrinsic deficit of optical emission.Comment: 8 pages, 3 figures (2 color), to be published in the Springer Lecture Notes of Physics Series as part of the proceedings for "ISO Surveys of a Dusty Universe," a workshop held at Ringberg Castle, Germany, November 8 - 12, 1999. Requires latex style files for this series: cl2emult.cls, cropmark.sty, lnp.sty, sprmindx.sty, subeqnar.sty (included with submission

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3&nbsp;years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6&nbsp;months (median). The median age was 72&nbsp;years, and the baseline median prostate-specific antigen level was 15.0&nbsp;ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7&nbsp;months (95% confidence interval [CI], 28.6-32.2&nbsp;months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7&nbsp;months (95% CI, 39.4-46.2&nbsp;months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow: results from a community based survey and laboratory surveillance

Background South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. Methods A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. Results In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. Conclusions South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.</p

Detection and metabolic investigations of a novel designer steroid: 3-chloro-17α-methyl-5α-androstan-17β-ol

In 2012, seized capsules containing white powder were analyzed to show the presence of unknown steroid-related compounds. Subsequent gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) investigations identified a mixture of 3α- and 3β- isomers of the novel compound; 3-chloro-17α-methyl-α-androstan-17β-ol. Synthesis of authentic reference materials followed by comparison of NMR, GC-MS and gas chromatography-tandem mass spectrometry (GC-MS/MS) data confirmed the finding of a new ‘designer’ steroid. Furthermore, in vitro androgen bioassays showed potent activity highlighting the potential for doping using this steroid. Due to the potential toxicity of the halogenated steroid, in vitro metabolic investigations of 3α-chloro-17α-methyl-α-androstan-17β-ol using equine and human S9 liver fractions were performed. For equine, GC-MS/MS analysis identified the diagnostic 3α-chloro-17α-methyl-5α-androstane-16α,17β-diol metabolite. For human, the 17α-methyl-α-androstane-3α,17β-diol metabolite was found. Results from these studies were used to verify the ability of GC-MS/MS precursor-ion scanning techniques to support untargeted detection strategies for designer steroids in anti-doping analyses.Synthesis and in vitro metabolic investigations of 3α/β-chloro-17α-methyl-5α-androstan -17β-ol was suppo rted by the Austr a-lian Research Council Linkage Grant (LP120200444) Strat egies for the detection of designer ster oids in ra cehorses