Encouraging Recruitment of Under-Represented Groups in Clinical Studies: A Sponsor\u27s Perspective

Researchers must strive to equally distribute both the costs and benefits of human subjects’ research among the population they serve. In the past, research studies disproportionally targeted convenient populations; participants were usually low-income and often minorities. Through a series of controversial and well known studies, protections were developed to better protect participants in research. However, these protections may have inadvertently caused a shift in the populations targeted for research. In recent history, women and minority groups have become under-represented in clinical research, particularly randomized controlled trials. This capstone seeks to explore the implications of under-representation of certain groups in research and how industry (Sponsor and CROs) can better address this disparity to increase the participation of these groups in clinical studies. Current federal and international policies regarding human subjects’ protections are documented and focuses on legislation in the United States that aims to increase the participation of women and minorities in research. The current costs and barriers to conducting a successful clinical trial, particularly as it pertains to recruitment of human subjects are explored. Using this information, the author proposes potential recommendations that could be incorporated at the industry level to successfully increase recruitment of under-represented groups in clinical trials. Sponsors must also consider limitations that may affect recruitment, such as provider implicit bias. Incorporation of comprehensive recruitment strategies are vital to the improvement of under-represented groups in clinical studies

A review of the mallet impact test for small scale explosive formulations

Presented at 19th Seminar on New Trends of Energetic Materials (NTREM 2016); 20-22/04/2016, Pardubice Czech RepublicDevelopment of new explosive formulations begins with the generation of only a few milligrams of material which is investigated using a number of small scale tests such as DSC, TGA, response to flame, mallet impact (mallet friction either glancing or direct blow) to determine whether the formulation is safe to scale up to 10 g. The latter of these tests, mallet impact, can be particularly subjective as the result is directly influenced by the operator carrying out the assessment. Not only can there be a change from one operator to another but there can also be a change in the force applied during each strike potentially leading to inconsistent results. This study highlights this encountered variation and assesses the load applied by a variety of operators with varying levels of explosive experience. This paper also proposes the use of a small scale laboratory based impact test which would provide improved confidence in the assessment of impact sensitiveness of explosive formulations and assist in justifying whether a formulation can be taken to the next scale. A small scale version of the BAM impact test (EMTAP Test 43) has been devised that allows the comparison of the sensitiveness of small scale formulations relative to RDX (8.7 J, EMTAP Test 43B) whilst also ensuring a reproducible result

Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process for both nicotine and alcohol. Considering the behavioral effects of NT69L in attenuating nicotine self-administration in rats and alcohol consumption in mice, the present study was designed to assess the effects of NT69L as a new drug. NT69L was used in the treatment of nicotine addiction in an animal model of alcoholics and in attempts to attenuate withdrawal signs associated with nicotine and alcohol dependence. Wistar rats pre-exposed to alcohol vapor or air were allowed to self-infuse nicotine (0.03mg/kg/infusion) or saline. When the rats reached a stable level of responding, the effect of pretreatment with NT69L (1mg/kg i.p.) on the reinforcing effect of nicotine was determined. Animals self-infused nicotine at a significantly (p \u3c .05) higher rate compared to saline in both air and alcohol vapor exposed groups. Acute pretreatment with a single injection of NT69L significantly (p \u3c .05) reduced nicotine self-infusion in both the alcohol vapor and the air exposed groups for 5 days post-injection. Additionally, NT69L attenuated the alcohol- and nicotine-induced withdrawal signs associated with the discontinuation of alcohol and nicotine administration. Neurotensin agonist, NT69L, may represent a potential novel therapy to treat the co-addiction of alcohol and nicotine

Antibiotic Discovery from the Abyss

It is essential that we discover and develop new antibiotics to overcome the problems associated with antibiotic resistance and find treatments for bacteria that don’t respond well to currently available treatment options. Recent years have seen revived interest in culture-dependent methods for discovery - screening rare bacteria from unexplored environments for their ability to inhibit the growth of pathogens. The deep sea is vast, rich in biodiversity, and one of the few ‘pristine’ environments on the planet. The extremophilic bacteria from this niche are likely metabolic innovators that evolved differently to terrestrial species, making them attractive sources of novel natural products.Our aims include (i) characterising the microbiome of deep-sea sponges, which have never been investigated before; (ii) culturing deep-sea bacteria and screening them for antibiotic production; (iii) genome sequencing and mining of producers to delineate the biosynthesis of novel antibiotics. This interdisciplinary project involves microbiology, bioinformatics, and analytical chemistry techniques.A recent screen of bacteria isolated from deep sea sponges found six strains that produce antibiotics under specific culture conditions. The genomes of these bacteria have been sequenced with Illumina and Nanopore technologies, and several active molecules have been purified. Our hit rate (8/487, or 1.6%) is higher than estimated for other environments, indicating that deep-sea sponges are a powerful source of biodiversity. Future work will involve linking natural products to biosynthetic gene clusters and transferring these clusters to heterologous hosts for larger scale production of antibiotics for method-of-action and efficacy studies.EPSRC, SynBio-CDT, DST

The Relationship of Lateral Eye Movements to Field-Dependence-Independence and Verbal and Performance Skills

Lateral eye movements and handedness as indexes of hemisphere asymmetry were compared to field-dependence-independence, as measured by Rod-and-Frame Test errors, and to Wechsler Verbal and Performance IQs. Consistent with previous research, the hypotheses predicted that persons with inconsistent lateral eye movements (ambilaterality) would have greater Rod-and-Frame errors (field-dependence) and lower Wechsler Verbal and Performance IQs. Subjects were 41 male undergraduates who were grouped according to their lateral eye movements in response to 20 reflective questions consisting of ten verbal (left-hemisphere) and ten spatial (right-hemisphere) questions. The response scoring resulted in 12 subjects with 70% or more lateral eye movements to the right who were classified as right-movers (left hemisphere dominant), 12 subjects with 70% or more lateral eye movements to the left who were classified as left-movers (right hemisphere dominant), and 17 subjects with inconsistent lateral eye movements who were classified as bidirectionals (ambilateral). Ambilaterals are assumed to have verbal functions equally represented in both hemispheres of the brain rather than left hemisphere specialization for that function. In addition to the subsequent administration of the handedness questionnaire, Rod-and-Frame Test, and the Wechsler, the existence of immediate or extended-family sinistrality (left-handedness) was also questioned. Statistical analysis by means of one-way analysis of variance, stepwise regression, and discriminant analysis yielded no significant differences between the three groups on measures of LEMs, handedness, Verbal IQ, Performance IQ, or Full Scale IQ. Chi square analysis of absence or presence of immediate or extended family sinistrality likewise yielded no significant results

The impact of the COVID-19 pandemic on oral health inequalities and access to oral healthcare in England

While the impact of the coronavirus disease (COVID-19) pandemic on health inequalities is documented, oral health has been absent from this discussion. This commentary highlights the potential impacts of the COVID-19 pandemic on oral health inequalities in England in February 2021. It includes a literature review, Public Health England and Kantar Worldpanel sales data on health behaviours and analysis of NHS dental services data. Purchasing data indicate, except for smoking, increases in health-compromising behaviours. Since the resumption of dental services, NHS general dental service use modestly recovered among adults but not children by October 2020. There are clear inequalities among children and older adults, with more deprived groups having lower uptake of dental service use than more affluent groups. Oral cancer referrals and hospital admissions for tooth extractions in children dramatically declined, with the latter primarily affecting children in more deprived areas. Many oral health programmes in schools and care homes were disrupted or suspended throughout this period. All these indicate that oral health inequalities have widened due to the COVID-19 pandemic. An oral health plan of action requires prioritising long-term investment in public health programmes and transforming commissioning pathways to support those with the greatest needs to access oral healthcare services

Synthesis and Characterization of Brannerite Wasteforms for the Immobilization of Mixed Oxide Fuel Residues

A possible method for the reduction of civil Pu stockpiles is the reuse of Pu in mixed oxide fuel (MOX). During MOX fuel production, residues unsuitable for further recycle will be produced. Due to their high actinide content MOX residues require immobilization within a robust host matrix. Although it is possible to immobilize actinides in vitreous wasteforms; ceramic phases, such as brannerite (UTi2O6), are attractive due to their high waste loading capacity and relative insolubility. A range of uranium brannerites, formulated GdxU1-xTi2O6, were prepared using a mixed oxide route. Charge compensation of divalent and trivalent cations was expected to occur via the oxidation of U4+ to higher valence states (U5+ or U6+). Gd3+ was added to act as a neutron absorber in the final Pu bearing wasteform. X-ray powder diffraction of synthesised specimens found that phase distribution was strongly affected by processing atmosphere (air or Ar). In all cases prototypical brannerite was formed accompanied by different secondary phases dependent on processing atmosphere. Microstructural analysis (SEM) of the sintered samples confirmed the results of the X-ray powder diffraction. The preliminary results presented here indicate that brannerite is a promising host matrix for mixed oxide fuel residues

Thermodynamics and mechanism of protonated cysteine decomposition: a guided ion beam and computational study

pre-printA quantitative molecular description of the decomposition of protonated cysteine, H+Cys, is provided by studying the kinetic energy dependence of threshold collision-induced dissociation (CID) with Xe using a guided ion beam tandem mass spectrometer (GIBMS). Primary dissociation channels are deamidation (yielding both NH3 loss and NH4 + formation) and (H2O + CO) loss reactions, followed by an additional six subsequent decompositions. Analysis of the kinetic energy-dependent CID cross sections provides the 0 K barriers for six different reactions after accounting for unimolecular decay rates, internal energy of reactant ions, multiple ion-molecule collisions, and competition among the decay channels. To identify the mechanisms associated with these reactions, quantum chemical calculations performed at the B3LYP/6-311+G(d,p) level were used to locate the transition states (TSs) and intermediates for these processes. Single point energies of the reactants, products, and key optimized TSs and intermediates are calculated at B3LYP, B3P86, and MP2(full) levels using a 6-311+G(2d,2p) basis set. The computational characterization of the elementary steps of these reactions including the structures of the final products is validated by quantitative agreement with the experimental energetics. In agreement with previous work, deamidation is facilitated by anchimeric assistance of the thio group, which also leads to an interesting rearrangement of the intact amino acid identified computationally