Synthetic Studies towards Trichothecene Mycotoxins

This thesis describes the first synthesis of a tetrahydroxylated trichothecene mycotoxin, 3alpha,4beta,8alpha,15-tetra-hydroxy-12,13-epoxy trichothec-9-ene (T-2 tetraol) (19), as its tetraacetate (Neosolaniol diacetate) (319) (Scheme 86). The synthetic strategy consists of five key elements. 1) formation of the cis fused AB ring system by a Diels-Alder cycloaddition; 2) formation of ring C by an intramolecular aldol reaction; 3) creation of the 3alpha,4beta-diol system of ring C by a stereoselective a-oxygenation/reduction protocol; 4) ring A enone formation via a regiospecific thermodynamically controlled alpha-selenylation, and 5) regio and stereospecific reduction of this enone to the required alpha-alcohol. As part of a concerted effort towards this molecule, this thesis reports a model study aimed at achieving the 3alpha,4beta-diol system of ring C (Scheme 52). The partial synthesis of 8-keto-anguidine (297) described herein (Chapter 2.2) allowed a study (Chapter 2.3) of the stereochemical outcome of the reduction of ring A enones by various reducing agents: it is shown that L-Selectride reduces such enones stereospecifically to 8alpha-alcohols. Attempted completion of an approach to deoxynivalenol (6) (Chapter 2.5) is discussed. The termination of this route is attributed to competing intramolecular processes which prevented successful olefination of the ketone (362)

Quinoline synthesis: scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes

Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo substituted annulated quinolines. para-Substituents yield 6-substituted-2,3-dihydro-1H-cyclopenta[b]quinolines with 8-substituted products being obtained from ortho-substituted starting materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents leading to 5-substituted 2,3-dihydro-1H-cyclopenta[b]quinolines and more strongly electron-donating substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene analogues yield annulated furo- and thieno-[2,3e]pyridines respectively. Sequential E- to Z-benzylidene group isomerisation and six [pi]-electron cyclisation steps result in formation of a short-lived dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol or acetic acid. For 2-benzylidenecyclopentanone O-allyloxime, singlet excited states are involved in both steps

The impact of believing you have had COVID-19 on self-reported behaviour: Cross-sectional survey.

OBJECTIVES: To investigate whether people who think they have had COVID-19 are less likely to report engaging with lockdown measures compared with those who think they have not had COVID-19. DESIGN: On-line cross-sectional survey. SETTING: Data were collected between 20th and 22nd April 2020. PARTICIPANTS: 6149 participants living in the UK aged 18 years or over. MAIN OUTCOME MEASURES: Perceived immunity to COVID-19, self-reported adherence to social distancing measures (going out for essential shopping, nonessential shopping, and meeting up with friends/family; total out-of-home activity), worry about COVID-19 and perceived risk of COVID-19 to oneself and people in the UK. Knowledge that cough and high temperature / fever are the main symptoms of COVID-19. We used logistic regression analyses and one-way ANOVAs to investigate associations between believing you had had COVID-19 and binary and continuous outcomes respectively. RESULTS: In this sample, 1493 people (24.3%) thought they had had COVID-19 but only 245 (4.0%) reported having received a positive test result. Reported test results were often incongruent with participants' belief that they had had COVID-19. People who believed that they had had COVID-19 were: more likely to agree that they had some immunity to COVID-19; less likely to report adhering to lockdown measures; less worried about COVID-19; and less likely to know that cough and high temperature / fever are two of the most common symptoms of COVID-19. CONCLUSIONS: At the time of data collection, the percentage of people in the UK who thought they had already had COVID-19 was about twice the estimated infection rate. Those who believed they had had COVID-19 were more likely to report leaving home. This may contribute to transmission of the virus. Clear communications to this growing group are needed to explain why protective measures continue to be important and to encourage sustained adherence

Identifying key health system components associated with improved outcomes to inform the reconfiguration of services for adults with rare autoimmune rheumatic diseases : a mixed methods study.

Open Access via the Elsevier agreementPeer reviewe

Pilot testing the feasibility of a game intervention aimed at improving help seeking and coping among sexual and gender minority youth: protocol for a randomized controlled trial

Background: Sexual and gender minority youth (SGMY; e.g., lesbian, gay, bisexual, and transgender youth) experience myriad substance use and mental health disparities compared with their cisgender (non-transgender) heterosexual peers. Despite much research showing these disparities are driven by experiences of bullying and cyberbullying victimization, few interventions have aimed to improve the health of bullied SGMY. One possible way to improve the health of bullied SGMY is via an online-accessible game intervention. Nevertheless, little research has examined the feasibility of using an online-accessible game intervention with SGMY. Objectives: To describe the protocol for a randomized controlled trial (RCT) pilot testing the feasibility and limited-efficacy of a game-based intervention for increasing help-seeking-related knowledge, intentions, self-efficacy, and behaviors, productive coping skills use, and coping flexibility, and reducing health risk factors and behaviors among SGMY. Methods: We enrolled 240 SGMY aged 14-18 years residing in the United States into a two-arm prospective RCT. The intervention is a theory-based, community-informed, computer-based, role playing game with three primary components: (1) encouraging help-seeking behaviors; (2) encouraging use of productive coping; and (3) raising awareness of online resources. SGMY randomized to both the intervention and control conditions will receive a list of SGMY-inclusive resources covering a variety of health-related topics. Control condition participants received only the list of resources. Notably, all study procedures are conducted online. We conveniently sampled SGMY using online website advertisements. Study assessments occur at enrollment, 1 month after enrollment, and 2 months after enrollment. The primary outcomes of this feasibility study include implementation procedures, game demand, and game acceptability. Secondary outcomes include help-seeking intentions, self-efficacy, and behaviors; productive coping strategies and coping flexibility; and knowledge and use of online resources. Tertiary outcomes include bullying and cyberbullying victimization; loneliness; mental health issues; substance use; and internalized sexual and gender minority stigma. Results: From April through July 2018, 240 participants were enrolled and randomized. Half of the enrolled participants (n=120) were randomized into the intervention condition, and half (n=120) into the control condition. At baseline, 52% of participants identified as gay or lesbian, 27% as bisexual, 24% as queer, and 12% as another non-heterosexual identity. Nearly half (47%) of participants were a gender minority, 37% were cisgender boys, and 16% were cisgender girls. There were no differences in demographic characteristics between intervention and control condition participants. Data collection is anticipated to end in November 2018. Conclusions: Online-accessible game interventions overcome common impediments of face-to-face interventions and present a unique opportunity to reach SGMY and improve their health. This trial will provide data on feasibility and limited-efficacy that can inform future online studies and a larger RCT aimed at improving health equity for SGMY. Trial Registration: ClinicalTrials.gov NCT03501264; https://clinicaltrials.gov/ct2/show/NCT03501264 (Archived by WebCite at http://www.webcitation.org/72HpafarW

The BLAST Survey of the Vela Molecular Cloud: Physical Properties of the Dense Cores in Vela-D

The Balloon-borne Large-Aperture Submillimeter Telescope (BLAST) carried out a 250, 350 and 500 micron survey of the galactic plane encompassing the Vela Molecular Ridge, with the primary goal of identifying the coldest dense cores possibly associated with the earliest stages of star formation. Here we present the results from observations of the Vela-D region, covering about 4 square degrees, in which we find 141 BLAST cores. We exploit existing data taken with the Spitzer MIPS, IRAC and SEST-SIMBA instruments to constrain their (single-temperature) spectral energy distributions, assuming a dust emissivity index beta = 2.0. This combination of data allows us to determine the temperature, luminosity and mass of each BLAST core, and also enables us to separate starless from proto-stellar sources. We also analyze the effects that the uncertainties on the derived physical parameters of the individual sources have on the overall physical properties of starless and proto-stellar cores, and we find that there appear to be a smooth transition from the pre- to the proto-stellar phase. In particular, for proto-stellar cores we find a correlation between the MIPS24 flux, associated with the central protostar, and the temperature of the dust envelope. We also find that the core mass function of the Vela-D cores has a slope consistent with other similar (sub)millimeter surveys.Comment: Accepted for publication in the Astrophysical Journal. Data and maps are available at http://blastexperiment.info

Reducing Baylisascaris procyonis Roundworm Larvae in Raccoon Latrines

Baylisascaris procyonis roundworms, a parasite of raccoons, can infect humans, sometimes fatally. Parasite eggs can remain viable in raccoon latrines for years. To develop a management technique for parasite eggs, we tested anthelmintic baiting. The prevalence of eggs decreased at latrines, and larval infections decreased among intermediate hosts, indicating that baiting is effective

BLAST: The Mass Function, Lifetimes, and Properties of Intermediate Mass Cores from a 50 Square Degree Submillimeter Galactic Survey in Vela (l = ~265)

We present first results from an unbiased 50 deg^2 submillimeter Galactic survey at 250, 350, and 500 micron from the 2006 flight of the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). The map has resolution ranging from 36 arcsec to 60 arcsec in the three submillimeter bands spanning the thermal emission peak of cold starless cores. We determine the temperature, luminosity, and mass of more than one thousand compact sources in a range of evolutionary stages and an unbiased statistical characterization of the population. From comparison with C^(18)O data, we find the dust opacity per gas mass, kappa r = 0.16 cm^2 g^(-1) at 250 micron, for cold clumps. We find that 2% of the mass of the molecular gas over this diverse region is in cores colder than 14 K, and that the mass function for these cold cores is consistent with a power law with index alpha = -3.22 +/- 0.14 over the mass range 14 M_sun < M < 80 M_sun. Additionally, we infer a mass-dependent cold core lifetime of t_c(M) = 4E6 (M/20 M_sun)^(-0.9) years - longer than what has been found in previous surveys of either low or high mass cores, and significantly longer than free fall or likely turbulent decay times. This implies some form of non-thermal support for cold cores during this early stage of star formation.Comment: Accepted for publication in the Astrophysical Journal. Maps available at http://blastexperiment.info