An exploration of function analysis and function allocation in the commercial flight domain

The applicability is explored of functional analysis methods to support cockpit design. Specifically, alternative techniques are studied for ensuring an effective division of responsibility between the flight crew and automation. A functional decomposition is performed of the commercial flight domain to provide the information necessary to support allocation decisions and demonstrate methodology for allocating functions to flight crew or to automation. The function analysis employed 'bottom up' and 'top down' analyses and demonstrated the comparability of identified functions, using the 'lift off' segment of the 'take off' phase as a test case. The normal flight mission and selected contingencies were addressed. Two alternative methods for using the functional description in the allocation of functions between man and machine were investigated. The two methods were compared in order to ascertain their relative strengths and weaknesses. Finally, conclusions were drawn regarding the practical utility of function analysis methods

Toxicology and Biodistribution Studies for MGH2.1, an Oncolytic Virus that Expresses Two Prodrug-activating Genes, in Combination with Prodrugs

MGH2.1 is a herpes simplex virus type 1 (HSV1) oncolytic virus that expresses two prodrug-activating transgenes: the cyclophosphamide (CPA)-activating cytochrome P4502B1 (CYP2B1) and the CPT11-activating secreted human intestinal carboxylesterase (shiCE). Toxicology and biodistribution of MGH2.1 in the presence/absence of prodrugs was evaluated in mice. MGH2.1 ± prodrugs was cytotoxic to human glioma cells, but not to normal cells. Pharmacokinetically, intracranial MGH2.1 did not significantly alter the metabolism of intraperitoneally (i.p.) administered prodrugs in mouse plasma, brain, or liver. MGH2.1 did not induce an acute inflammatory reaction. MGH2.1 DNA was detected in brains of mice inoculated with 108 pfus for up to 60 days. However, only one animal showed evidence of viral gene expression at this time. Expression of virally encoded genes was restricted to brain. Intracranial inoculation of MGH2.1 did not induce lethality at 108 pfus in the absence of prodrugs and at 106 pfus in the presence of prodrugs. This study provides safety and toxicology data justifying a possible clinical trial of intratumoral injection of MGH2.1 with peripheral administration of CPA and/or CPT11 prodrugs in humans with malignant gliomas

Community as a source of health in three racial/ethnic communities in Oregon: a qualitative study

BACKGROUND: A 2011 report by the Oregon Health Authority and the Department of Human Services documented disparities in its Latino and American Indian populations on multiple individual-level health indicators. However, research is lacking on the social contexts in which Latinos and American Indians in Oregon live and how these environments influence the health of communities as a whole. To help fill this gap, this study sought to contextualize the social environments that influence the health of Latinos and American Indian residents in three Oregon communities. METHODS: Guided by an ecological framework, we conducted one-time semi-structured qualitative interviews with 26 study participants to identify the prominent health-related issues in the communities and to examine the factors that study participants perceived as enabling or inhibiting healthy lifestyles of community residents. We used a grounded theory approach to perform content and thematic analyses of the data. RESULTS: Study participants identified preventable chronic conditions, such as diabetes, obesity, and hypertension, as the most pressing health concerns in their communities. Results showed that traditional and cultural activities and strong family and community cohesion were viewed as facilitators of good community health. Poverty, safety concerns, insufficient community resources, and discrimination were perceived as barriers to community health. Three themes emerged from the thematic analyses: social connectedness is integral to health; trauma has an ongoing negative impact on health; and invisibility of residents in the community underlies poor health. CONCLUSIONS: This study’s findings provide insight to the social contexts which operate in the lives of some Latinos and American Indians in Oregon. While participants identified community-level factors as important to health, they focused more on the social connections of individuals to each other and the relationships that residents have with their communities at-large. Our findings may also help to explain how the intra- and inter-personal levels, the community/institutional level, and the macro level/public policy contexts can serve to influence health in these communities. For example, trauma and invisibility are not routinely examined in community health assessment and improvement planning activities; nonetheless, these factors appear to be at play affecting the health of residents.Keywords: American Indian, Latino, Migrant and seasonal farmworkers, Trauma, Community healt

In search of meaningful work on digital freelancing platforms: the case of design professionals

Growth of the platform economy has been accompanied by critiques of the fragmented, isolated and precarious nature of the employment it offers. Yet, little is known about how creative freelancers perceive the meaning of work on the platforms. Based on 40 interviews with freelancers, clients, platform owners and industry experts, this paper reveals that most freelancers are concerned about how operating through the platform, and their dependence on it, is undermining the meaningfulness of their work. Freelancers find that the platforms are eroding both the manifest (i.e. monetary) and latent (i.e. non‐monetary) meaning of their work although they are mostly concerned about the latent element of meaning. The analysis reveals that the small group of freelancers who pursue meaningful work and earn a sustainable income on platforms are those with strong entrepreneurial orientation

Oncolytic HSV Vectors and Anti-Tumor Immunity

The therapeutic promise of oncolytic viruses (OVs) rests on their ability to both selectively kill tumor cells and induce anti-tumor immunity. The potential of tumors to be recognized and eliminated by an effective anti-tumor immune response has been spurred on by the discovery that immune checkpoint inhibition can overcome tumor-specific cytotoxic T cell (CTL) exhaustion and provide durable responses in multiple tumor indications. OV-mediated tumor destruction is now recognized as a powerful means to assist in the development of anti-tumor immunity for two important reasons: (i) OVs, through the elicitation of an anti-viral response and the production of type I interferon, are potent stimulators of inflammation and can be armed with transgenes to further enhance anti-tumor immune responses; and (ii) lytic activity can promote the release of tumor-associated antigens (TAAs) and tumor neoantigens that function as in situ tumor-specific vaccines to elicit adaptive immunity. Oncolytic herpes simplex viruses (oHSVs) are among the most widely studied OVs for the treatment of solid malignancies, and Amgen's oHSV Imlygic® for the treatment of melanoma is the only OV approved in major markets. Here we describe important biological features of HSV that make it an attractive OV, clinical experience with HSV-based vectors, and strategies to increase applicability to cancer treatment

Access to primary care for socio-economically disadvantaged older people in rural areas: a qualitative study

Objective: We aim to explore the barriers to accessing primary care for socio-economically disadvantaged older people in rural areas. Methods: Using a community recruitment strategy, fifteen people over 65 years, living in a rural area, and receiving financial support were recruited for semi-structured interviews. Four focus groups were held with rural health professionals. Interviews and focus groups were audio-recorded and transcribed. Thematic analysis was used to identify barriers to primary care access. Findings: Older people’s experience can be understood within the context of a patient perceived set of unwritten rules or social contract – an individual is careful not to bother the doctor in return for additional goodwill when they become unwell. However, most found it difficult to access primary care due to engaged telephone lines, availability of appointments, interactions with receptionists; breaching their perceived social contract. This left some feeling unwelcome, worthless or marginalised, especially those with high expectations of the social contract or limited resources, skills and/or desire to adapt to service changes Health professionals’ described how rising demands and expectations coupled with service constraints had necessitated service development, such as fewer home visits, more telephone consultations, triaging calls and modifying the appointment system. Conclusion: Multiple barriers to accessing primary care exist for this group. As primary care is re-organised to reduce costs, commissioners and practitioners must not lose sight of the perceived social contract and models of care that form the basis of how many older people interact with the service

Co-designing Urban Living Solutions to Improve Older People’s Mobility and Well-Being

Mobility is a key aspect of active ageing enabling participation and autonomy into later life. Remaining active brings multiple physical but also social benefits leading to higher levels of well-being. With globally increasing levels of urbanisation alongside demographic shifts meaning in many parts of the world this urban population will be older people, the challenge is how cities should evolve to enable so-called active ageing. This paper reports on a co-design study with 117 participants investigating the interaction of existing urban spaces and infrastructure on mobility and well-being for older residents (aged 55 + years) in three cities. A mixed method approach was trialled to identify locations beneficial to subjective well-being and participant-led solutions to urban mobility challenges. Spatial analysis was used to identify key underlying factors in locations and infrastructure that promoted or compromised mobility and well-being for participants. Co-designed solutions were assessed for acceptability or co-benefits amongst a wider cross-section of urban residents (n = 233) using online and face-to-face surveys in each conurbation. Our analysis identified three critical intersecting and interacting thematic problems for urban mobility amongst older people: The quality of physical infrastructure; issues around the delivery, governance and quality of urban systems and services; and the attitudes and behaviors of individuals that older people encounter. This identified complexity reinforces the need for policy responses that may not necessarily involve design or retrofit measures, but instead might challenge perceptions and behaviors of use and access to urban space. Our co-design results further highlight that solutions need to move beyond the generic and placeless, instead embedding specific locally relevant solutions in inherently geographical spaces, populations and processes to ensure they relate to the intricacies of place

A qualitative study of naturopathy in rural practice: A focus upon naturopaths' experiences and perceptions of rural patients and demands for their services

Background. Complementary and alternative medicine (CAM) use - of which naturopathy constitutes a significant proportion - accounts for approximately half of all health consultations and half of out-of-pocket expenditure in Australia. Data also suggest CAM use is highest amongst rural Australians. Unfortunately little is known about the grass-roots reality of naturopathy or other CAM use in rural regions. Methods. Semi-structured interviews were conducted with 20 naturopaths practising in the Darling Downs region of South-East Queensland to assess their perceptions and experiences of rural patients and demand for their services. Results. Naturopaths described strong demand in rural areas for their services and perceived much of this demand as attributable to cultural traits in rural communities that served as pull factors for their naturopathic services. Such perceived traits included a cultural affinity for holistic approaches to health and disease and the preventive philosophy of naturopathy and an appreciation of the core tenet of naturopathic practice to develop closer therapeutic relationships. However, cost and a rural culture of self-reliance were seen as major barriers to naturopathic practice in rural areas. Conclusions. Demand for naturopathic services in rural areas may have strong underlying cultural and social drivers. Given the apparent affinity for and increasingly large role played by CAM services, including naturopathic medicine, in rural areas it is imperative that naturopathic medicine and the CAM sector more broadly become a core focus of rural health research

Horizontal Transmission of Candida albicans and Evidence of a Vaccine Response in Mice Colonized with the Fungus

Disseminated candidiasis is the third leading nosocomial blood stream infection in the United States and is often fatal. We previously showed that disseminated candidiasis was preventable in normal mice by immunization with either a glycopeptide or a peptide synthetic vaccine, both of which were Candida albicans cell wall derived. A weakness of these studies is that, unlike humans, mice do not have a C. albicans GI flora and they lack Candida serum antibodies. We examined the influence of C. albicans GI tract colonization and serum antibodies on mouse vaccination responses to the peptide, Fba, derived from fructose bisphosphate aldolase which has cytosolic and cell wall distributions in the fungus. We evaluated the effect of live C. albicans in drinking water and antimicrobial agents on establishment of Candida colonization of the mouse GI tract. Body mass, C. albicans in feces, and fungal-specific serum antibodies were monitored longitudinally. Unexpectedly, C. albicans colonization occurred in mice that received only antibiotics in their drinking water, provided that the mice were housed in the same room as intentionally colonized mice. The fungal strain in unintentionally colonized mice appeared identical to the strain used for intentional GI-tract colonization. This is the first report of horizontal transmission and spontaneous C. albicans colonization in mice. Importantly, many Candida-colonized mice developed serum fungal-specific antibodies. Despite the GI-tract colonization and presence of serum antibodies, the animals made antibodies in response to the Fba immunogen. This mouse model has potential for elucidating C. albicans horizontal transmission and for exploring factors that induce host defense against disseminated candidiasis. Furthermore, a combined protracted GI-tract colonization with Candida and the possibility of serum antibody responses to the presence of the fungus makes this an attractive mouse model for testing the efficacy of vaccines designed to prevent human disseminated candidiasis