A study for development of aerothermodynamic test model materials and fabrication technique

A literature survey, materials reformulation and tailoring, fabrication problems, and materials selection and evaluation for fabricating models to be used with the phase-change technique for obtaining quantitative aerodynamic heat transfer data are presented. The study resulted in the selection of two best materials, stycast 2762 FT, and an alumina ceramic. Characteristics of these materials and detailed fabrication methods are presented

A racial and urban-rural comparison of the nature of stroke in South Africa

ABSTRACT Sub-Saharan Africa is thought to be undergoing a health (or epidemiological) and demographic transition, moving from a pattern of disease dominated by infection, perinatal illness and other diseases of poverty, to one dominated by noncommunicable disease, in particular vascular disease. If such a transition is occurring, then the burden of vascular disease including stroke will increase. Stroke is a heterogeneous condition and it is likely that the nature of stroke (pathological types, subtypes, and causes) will change during this transition. However, little is known about the burden and nature of stroke in Sub-Saharan Africa, as it is now. This information is essential to inform health services to appropriately plan and deliver health care for the future, to develop strategies for stroke prevention, and to test the theory of the health and demographic transition. My overall aim was to assess and compare the burden and nature of stroke in rural and urban South Africa, and to establish whether there is any evidence of a health transition. Specifically I aimed to: • review what is known about stroke in Sub-Saharan Africa; • establish the prevalence and nature of prevalent stroke in rural South Africa; • compare the nature of hospital-based stroke in urban and rural stroke patients; • compare the nature of urban hospital-based stroke in different population groups; and • validate two stroke scores in the urban stroke register to enable us to diagnose pathological stroke type in rural stroke patients who do not have access to brain imaging. Methods: The following methods were used to achieve these aims: • I systematically searched the literature for, and critically reviewed, studies of stroke from Sub-Saharan Africa (literature review). • The rural Agincourt Health and Population Unit demographic surveillance site was screened for stroke using two questions during the annual census. Anyone who screened positive for stroke was examined to decide whether they had had a stroke (stroke prevalence study). • The Tintswalo Hospital Stroke Register was established to ascertain and assess rural stroke patients over 20 months (rural hospital-based stroke), and • The Johannesburg Hospital Stroke Register similarly established to assess urban stroke patients over 23 months (urban hospital-based stroke). • The accuracy of the Siriraj and Guy’s Hospital stroke scores was compared to the CT brain scan “gold-standard” in the Johannesburg Hospital Stroke Register. Results: Using these approaches I found that: • Very little is currently known about the burden and nature of stroke in Sub- Saharan Africa. • The prevalence of rural stroke was about half that found in high-income countries, and double that found in Tanzania. However, disabling stroke was at least as prevalent as it is in high-income countries. • Both rural and urban black South Africans are probably in early phases of the health transition, and this is impacting on the nature of stroke, particularly the cause of cardioembolic stroke. • Neither the Siriraj nor Guy’s Hospital stroke score are sufficiently accurate for use in epidemiological studies or clinical management of stroke in Sub- Saharan Africa. Conclusion: There is already a heavy burden of stroke in Sub-Saharan Africa, and there is some evidence of a health transition in the black population. However, it is not possible to accurately assess the burden and nature of stroke without communitybased incidence studies using early brain imaging to distinguish ischaemic stroke from cerebral haemorrhage. Until we have these studies, we will never know the precise burden and nature of stroke, the effect of the health transition, or the optimal approach to preventing a stroke epidemic in our population

Extracellular vesicles, microRNA and the preimplantation embryo: non-invasive clues of embryo well-being

Elective single embryo transfer is rapidly becoming the standard of care in assisted reproductive technology for patients under the age of 35 years with a good prognosis. Clinical pregnancy rates have become increasingly dependent on the selection of a single viable embryo for transfer, and diagnostic techniques facilitating this selection continue to develop. Current progress in elucidating the extracellular vesicle and microRNA components of the embryonic secretome is reviewed, and the potential for these findings to improve clinical embryo selection discussed. Key results have shown that extracellular vesicles and microRNAs are rapidly detectable constituents of the embryonic secretome. Evidence suggests that the vesicular population is largely exosomal in nature, secreted at all stages of preimplantation development and capable of traversing the zona pellucida. Both extracellular vesicle and microRNA concentrations within the secretome are elevated for blastocysts with diminished developmental competence, as indicated either by degeneracy or implantation failure, whereas studies have yet to firmly correlate individual microRNA sequences with pregnancy outcome. These emerging correlations support the viability of extracellular vesicles and microRNAs as the basis for a new diagnostic test to supplement or replace morphokinetic assessment

Novel application of synchrotron x-ray computed tomography for ex-vivo imaging of subcutaneously-injected polymeric microsphere suspension formulations

Purpose: Subcutaneously or intramuscularly administered biodegradable microsphere formulations have been successfully exploited in the management of chronic conditions for over two decades, yet mechanistic understanding of the impact of formulation attributes on in vivo absorption rate from such systems is still in its infancy. Methods: Suspension formulation physicochemical attributes may impact particulate deposition in subcutaneous (s.c.) tissue. Hence, the utility of synchrotron X-ray microcomputed tomography (μCT) for assessment of spatial distribution of suspension formulation components (PLG microspheres and vehicle) was evaluated in a porcine s.c. tissue model. Optical imaging of dyed vehicle and subsequent microscopic assessment of microsphere deposition was performed in parallel to compare the two approaches. Results: Our findings demonstrate that synchrotron μCT can be applied to the assessment of microsphere and vehicle distribution in s.c. tissue, and that microspheres can also be visualised in the absence of contrast agent using this approach. The technique was deemed superior to optical imaging of macrotomy for the characterisation of microsphere deposition owing to its non-invasive nature and relatively rapid data acquisition time. Conclusions: The μCT method outlined in this study provides a novel insight into the relative distribution of vehicle and suspended PLG microspheres following s.c. injection. A potential application for our findings is understanding the impact of injection, device and formulation variables on initial and temporal depot geometry in pre-clinical or ex-vivo models that can inform product design

Murine Blastocysts Release Mature MicroRNAs Into Culture Media That Reflect Developmental Status

Extracellular microRNA (miRNA) sequences derived from the pre-implantation embryo have attracted interest for their possible contributions to the ongoing embryonic–uterine milieu, as well as their potential for use as accessible biomarkers indicative of embryonic health. Spent culture media microdroplets used to culture late-stage E4.0 murine blastocysts were screened for 641 mature miRNA sequences using a reverse transcription–quantitative polymerase chain reaction–based array. We report here 39 miRNAs exclusively detected in the conditioned media, including the implantation-relevant miR-126a-3p, miR-101a, miR-143, and miR-320, in addition to members of the highly expressed embryonic miR-125 and miR-290 families. Based on these results, an miRNA panel was assembled comprising five members of the miR-290 family (miR-291-295) and five conserved sequences with significance to the embryonic secretome (miR-20a, miR-30c, miR-142-3p, miR-191, and miR-320). Panel profiling of developing embryo cohort lysates and accompanying conditioned media microdroplets revealed extensive similarities in relative quantities of miRNAs and, as a biomarker proof of concept, enabled distinction between media conditioned with differently staged embryos (zygote, 4-cell, and blastocyst). When used to assess media conditioned with embryos of varying degrees of degeneration, the panel revealed increases in all extracellular panel sequences, suggesting cell death is an influential and identifiable factor detectable by this assessment. In situ hybridization of three panel sequences (miR-30c, miR-294, and miR-295) in late-stage blastocysts revealed primarily inner cell mass expression with a significant presence of miR-294 throughout the blastocyst cavity. Furthermore, extracellular miR-290 sequences responded significantly to high centrifugal force, suggesting a substantial fraction of these sequences may exist within a vesicle such as an exosome, microvesicle, or apoptotic bleb. Together, these results support the use of extracellular miRNA to assess embryonic health and enable development of a non-invasive viability diagnostic tool for clinical use

Testing the Drosophila maternal haploid gene for functional divergence and a role in hybrid incompatibility

Crosses between Drosophila simulans females and Drosophila melanogaster males produce viable F1 sons and poorly viable F1 daughters. Unlike most hybrid incompatibilities, this hybrid incompatibility violates Haldane’s rule, the observation that incompatibilities preferentially affect the heterogametic sex. Furthermore, it has a different genetic basis than hybrid lethality in the reciprocal cross, with the causal allele in Drosophila melanogaster being a large species-specific block of complex satellite DNA on its X chromosome known as the 359-bp satellite, rather than a protein-coding locus. The causal allele(s) in Drosophila simulans are unknown but likely involve maternally expressed genes or factors since the F1 females die during early embryogenesis. The maternal haploid (mh) gene is an intriguing candidate because it is expressed maternally and its protein product localizes to the 359-bp repeat. We found that this gene has diverged extensively between Drosophila melanogaster and Drosophila simulans. This observation led to the hypothesis that Drosophila melanogaster mh may have coevolved with the 359-bp repeat and that hybrid incompatibility thus results from the absence of a coevolved mh allele in Drosophila simulans. We tested for the functional divergence of mh by creating matched transformants of Drosophila melanogaster and Drosophila simulans orthologs in both Drosophila melanogaster and Drosophila simulans strains. Surprisingly, we find that Drosophila simulans mh fully complements the female sterile phenotype of Drosophila melanogaster mh mutations. Contrary to our hypothesis, we find no evidence that adding a Drosophila melanogaster mh gene to Drosophila simulans increases hybrid viability

A Pilot Program For The Recruitment and Education of Navy Veterans Based on System-Level Technical Expertise and Leadership Maturation Developed During Service

The project, Stern2STEM, aims to advance STEM (Science, Technology, Engineering, and Mathematics) education through the preparation of student veterans to pursue baccalaureate STEM degrees and support the re-employment of these veterans into the Department of Defense (DoD) and the wider defense support industry. The program builds on the training that veterans have received in highly skilled technical areas, both in the classroom and “on-the-job”, to develop system level expertise in their respective technical disciplines. Key components of the program include: (1) establishing a mechanism for outreach and recruitment; (2) providing leveling, tutoring, mentoring, and support for students; (3) teaching and learning through proven pedagogical practices and through sound academic advising; (4) partnering with the DoD community to facilitate student career placement in the DoD STEM workforce; (5) providing workforce development for DoD STEM professionals. This paper will discuss the academic challenges that student veterans face while in higher education and the current STEM pipelines as students move through their college to professional careers. The early impact of academic tutoring, professional advising, mentorship, career placement, and recruitment of current service members into STEM disciplines through involvement with Stern2STEM will be discussed. Through Stern2STEM’s systematic interventions, the project has the potential to have a significant impact on the broader STEM education community as many of the principles, lessons learned, and tools developed will prove valuable for institutions which have a large population of student veterans

Does naltrexone treatment lead to depression? Findings from a randomized controlled trial in subjects with opioid dependence

Objective: Dysphoria and depression have been cited as side effects of the opioid antagonist naltrexone. We aimed to assess whether depressive symptoms are a clinically relevant side effect in a population receiving naltrexone as a treatment for opioid dependence. Methods: We carried out a randomized controlled, open-label trial comparing rapid opiate detoxification under anesthesia and naltrexone treatment with continued methadone maintenance at the Alcohol and Drug Service, Royal Brisbane and Women's Hospital, Brisbane, Australia. The study subjects were patients stabilized on methadone maintenance treatment for heroin dependence who wished to transfer to naltrexone treatment. The Beck Depression Inventory, State-Trait Anxiety Inventory and Opiate Treatment Index subscales for heroin use and social functioning were used at baseline and follow-up assessments at 1, 2, 3 and 6 months. Results: Forty-two participants were allocated to receive naltrexone treatment, whereas 38 continued methadone maintenance as the control condition. Participants who received naltrexone did not exhibit worsening of depressive symptoms. In participants attending all follow-up assessments, there was a trend for those receiving naltrexone to exhibit an improvement in depression over time compared with the control group. Participants who were adherent to naltrexone treatment exhibited fewer depressive symptoms than those who were nonadherent. Conclusions: These results suggest that depression need not be considered a common adverse effect of naltrexone treatment or a treatment contraindication and that engaging with or adhering to naltrexone treatment may be associated with fewer depressive symptoms

Radioactive Source Localisation via Projective Linear Reconstruction

Radiation mapping, through the detection of ionising gamma-ray emissions, is an important technique used across the nuclear industry to characterise environments over a range of length scales. In complex scenarios, the precise localisation and activity of radiological sources becomes difficult to determine due to the inability to directly image gamma photon emissions. This is a result of the potentially unknown number of sources combined with uncertainties associated with the source-detector separation—causing an apparent ‘blurring’ of the as-detected radiation field relative to the true distribution. Accurate delimitation of distinct sources is important for decommissioning, waste processing, and homeland security. Therefore, methods for estimating the precise, ‘true’ solution from radiation mapping measurements are required. Herein is presented a computational method of enhanced radiological source localisation from scanning survey measurements conducted with a robotic arm. The procedure uses an experimentally derived Detector Response Function (DRF) to perform a randomised-Kaczmarz deconvolution from robotically acquired radiation field measurements. The performance of the process is assessed on radiation maps obtained from a series of emulated waste processing scenarios. The results demonstrate a Projective Linear Reconstruction (PLR) algorithm can successfully locate a series of point sources to within 2 cm of the true locations, corresponding to resolution enhancements of between 5× and 10×