Preliminary design of a Flox disconnect for a Flox-Atlas vehicle Final report

Fluorine-liquid oxygen disconnect for Atlas launch vehicle oxidizer syste

A set of ontologies to drive tools for the control of vector-borne diseases

We are developing a set of ontologies that deal with vector-borne diseases and the arthropod vectors that transmit them. For practical reasons (application priorities), we initiated this project with an ontology of insecticide resistance followed by a series of ontologies that describe malaria as well as physiological processes of mosquitoes that are relevant to, and involved in, disease transmission. These will be expanded to encompass other vector-borne diseases as well as non-mosquito vectors. The aim of the whole undertaking, which is worked out in the frame of the international IDO (Infectious Disease Ontology) project, is to provide the community with a set of ontological tools that can be used both in the development of specific databases and, most importantly, in the construction of decision support systems to control these diseases

Designing and Implementing a Longitudinal Study of Children with Neurological, Genetic, or Metabolic Conditions: \u3cem\u3eCharting the Territory\u3c/em\u3e

Background: Children with progressive metabolic, neurological, or chromosomal conditions and their families anticipate an unknown lifespan, endure unstable and often painful symptoms, and cope with erratic emotional and spiritual crises as the condition progresses along an uncertain trajectory towards death. Much is known about the genetics and pathophysiology of these diseases, but very little has been documented about the trajectory of symptoms for children with these conditions or the associated experience of their families. A longitudinal study design will help to close this gap in knowledge. Methods/Design: Charting the Territory is a longitudinal descriptive, correlational study currently underway with children 0–19 years who are diagnosed with progressive neurological, metabolic, or chromosomal conditions and their families. The purpose of the study is to determine and document the clinical progression of the condition and the associated bio psychosocial spiritual experiences of these parents and siblings age 7–18 years. Approximately 300 families, both newly diagnosed children and those with established conditions, are being recruited in six Canadian cities. Children and their families are being followed for a minimum of 18 months, depending on when they enroll in the study. Family data collection will continue after the child’s death if the child dies during the study period. Data collection includes monthly parental assessment of the child’s symptoms; an annual functional assessment of the child; and completion of established instruments every 6 months by parents to assess family functioning, marital satisfaction, health status, anxiety, depression, stress, burden, grief, spirituality, and growth, and by siblings to assess coping and health. Impact of participation on parents is assessed after 1 year and at the end of the study. Chart reviews are conducted at enrollment and at the conclusion of the study or at the time of the child’s death. Discussion: Knowledge developed from this study will provide some of the first ever detailed descriptions of the clinical symptom trajectory of these non-curable progressive conditions and the bio-psychosocial spiritual aspects for families, from diagnosis through bereavement. Information about developing and implementing this study may be useful to other researchers who are interested in designing a longitudinal study

Innovations in Research with Medically Fragile Populations: Using Bulletin Board Focus Groups

A new group of medically fragile young adults are graduating from pediatric palliative care programs with limited expectations to live beyond early adulthood, and no comparable adult services to support their complex needs. Accessing this population is difficult because of the complexity of their conditions, the extensive personal and equipment supports that limit feasibility for travel, and divergent communication abilities. Therefore, we undertook a descriptive case study using an asynchronous modification of an online focus group, a bulletin board focus group (BBFG). The greatest strengths of the BBFG are the appeal of this methodology for young adults and the multi day focus group becomes both a community and an intervention. An important limitation of this method was participant follow through on discussion threads. This BBFG provided rich and varied types of data, and very positive participant experiences

Tamoxifen-like metallocifens target thioredoxin system determining mitochondrial impairment leading to apoptosis in Jurkat cells

Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, and Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. In contrast, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types resistant to standard chemotherapies. Therefore, we investigated the effect of these three TLMs on the thioredoxin system and evaluated the input of the metallocene unit in comparison with structurally related organic tamoxifens. In vitro, all three TLMs became strong inhibitors of the cytosolic (TrxR1) and mitochondrial (TrxR2) isoforms of thioredoxin reductase after enzymatic oxidation with HRP/H2O2 while none of the organic analogues was effective. In Jurkat cells, TLMs inhibited mainly TrxR2, resulting in the accumulation of oxidized thioredoxin 2 and cell redox imbalance. Overproduction of ROS resulted in a strong decrease in the mitochondrial membrane potential, translocation of cytochrome c to the cytosol and activation of caspase 3, thus leading to apoptosis. None of these events occurred with organic tamoxifens. The mitochondrial fraction of cells exposed to TLMs contained a high amount of the corresponding metal, as quantified by ICP-OES. The lipophilic and cationic character associated with the singular redox properties of the TLMs could explain why they alter the mitochondrial function. These results provide new insights into the mechanism of action of tamoxifen-like metallocifens, underlying their prodrug behaviour and the pivotal role played by the metallocenic entity in their cytotoxic activity associated with the induction of apoptosis

Conceptual design of an orbital propellant transfer experiment. Volume 2: Study results

The OTV configurations, operations and requirements planned for the period from the 1980's to the 1990's were reviewed and a propellant transfer experiment was designed that would support the needs of these advanced OTV operational concepts. An overall integrated propellant management technology plan for all NASA centers was developed. The preliminary cost estimate (for planning purposes only) is $56.7 M, of which approximately$31.8 M is for shuttle user costs

Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion

Apicomplexan parasites critically depend on a unique form of gliding motility to colonize their hosts and to invade cells. Gliding requires different stage and species-specific transmembrane adhesins, which interact with an intracellular motor complex shared across parasite stages and species. How gliding is regulated by extracellular factors and intracellular signalling mechanisms is largely unknown, but current evidence suggests an important role for cytosolic calcium as a second messenger. Studying a Plasmodium berghei gene deletion mutant, we here provide evidence that a calcium-dependent protein kinase, CDPK3, has an important function in regulating motility of the ookinete in the mosquito midgut. We show that a cdpk3(–) parasite clone produces morphologically normal ookinetes, which fail to engage the midgut epithelium, due to a marked reduction in their ability to glide productively, resulting in marked reduction in malaria transmission to the mosquito. The mutant was successfully complemented with an episomally maintained cdpk3 gene, restoring mosquito transmission to wild-type level. cdpk3(–) ookinetes maintain their full genetic differentiation potential when microinjected into the mosquito haemocoel and cdpk3(–) sporozoites produced in this way are motile and infectious, suggesting an ookinete-limited essential function for CDPK3

A Scoping Review Exploration of the Intended and Unintended Consequences of eHealth on Older People:A Health Equity Impact Assessment

eHealth is one perceived mechanism to extend the range and reach of limited health-care resources for older adults. A decade-scoping review (2007–2017) was conducted to systematically search and synthesize evidence to understand the intended and unintended consequences of eHealth initiatives, informed by a health equity impact assessment framework. Scoping review sources included international academic and grey literature on eHealth initiatives (e.g., eHealth records, telemedicine/telecare, and mobile eHealth application) focused on the varying needs of older adults (aged 60+), particularly individuals experiencing sociocultural and economic difficulties. Findings suggest that eHealth has several potential benefits for older adults, but also the possibility of further excluding already marginalized groups, thereby exacerbating existing health disparities. Ongoing evaluation of eHealth initiatives for older adults is necessary and requires attention to unique individual-level, socioeconomic, and cultural characteristics to heighten benefits and better capture both the intended and unintended outcomes of advanced eHealth systems.peerReviewe

Research Priorities in Pediatric Palliative Care: A Delphi Study

Pediatric palliative care is increasingly recognized to be a specialized type of care requiring specific skills and knowledge, yet, as found in several countries, there is little available research evidence on which to base care. Objectives: The goal of the project was to achieve consensus among palliative care practitioners and researchers regarding the identification of pertinents lines of research. Method: A Delphi technique was used with an interdisciplinary panel (n=14–16) of researchers and frontline clinicians in pediatric palliative care in Canada. Results: Four priority research questions were identified: What matters most for patients and parents receiving pediatric palliative services? What are the bereavement needs of families in pediatric palliative care? What are the best practice standards in pain and symptom management? What are effective strategies to alleviate suffering at the end of life? Conclusions: These identified priorities will provide guidance and direction for research efforts in Canada, and may prove useful in providing optimal care to patients and families in pediatric palliative care

Distinct effects of HIV protease inhibitors and ERAD inhibitors on zygote to ookinete transition of the malaria parasite

In an effort to eradicate malaria, new interventions are proposed to include compound/vaccine development against pre-erythrocytic, erythrocytic and mosquito stages of Plasmodium. Drug repurposing might be an alternative approach to new antimalarials reducing the cost and the time required for drug development. Previous in vitro studies have examined the effects of protease inhibitors on different stages of the Plasmodium parasite, although the clinical relevance of this remains unclear. In this study we tested the putative effect of three HIV protease inhibitors, two general aspartyl protease inhibitors and three AAA-p97 ATPase inhibitors on the zygote to ookinete transition of the Plasmodium parasite. Apart from the two general aspartyl inhibitors, all other compounds had a profound effect on the development of the parasites. HIVPIs inhibited zygote to ookinete conversion by 75%–90%, while the three AAA-p97 ATPase inhibitors blocked conversion by 50%–90% at similar concentrations, while electron microscopy highlighted nuclear and structural abnormalities. Our results highlight a potential of HIV protease inhibitors and p97 inhibitors as transmission blocking agents for the eradication of malaria