Different genetic mechanisms mediate spontaneous versus UVR-induced malignant melanoma

Genetic variation conferring resistance and susceptibility to carcinogen-induced tumorigenesis is frequently studied in mice. We have now turned this idea to melanoma using the collaborative cross (CC), a resource of mouse strains designed to discover genes for complex diseases. We studied melanoma-prone transgenic progeny across seventy CC genetic backgrounds. We mapped a strong quantitative trait locus for rapid onset spontaneous melanoma onset to Prkdc, a gene involved in detection and repair of DNA damage. In contrast, rapid onset UVR-induced melanoma was linked to the ribosomal subunit gene Rrp15. Ribosome biogenesis was upregulated in skin shortly after UVR exposure. Mechanistically, variation in the ‘usual suspects’ by which UVR may exacerbate melanoma, defective DNA repair, melanocyte proliferation, or inflammatory cell infiltration, did not explain melanoma susceptibility or resistance across the CC. Instead, events occurring soon after exposure, such as dysregulation of ribosome function, which alters many aspects of cellular metabolism, may be important

Transport behavior of holes in boron delta-doped diamond structures

Boron delta-doped diamond structures have been synthesized using microwave plasma chemical vapor deposition and fabricated into FET and gated Hall bar devices for assessment of the electrical characteristics. A detailed study of variable temperature Hall, conductivity, and field-effect mobility measurements was completed. This was supported by Schr€dinger-Poisson and relaxation time o calculations based upon application of Fermi’s golden rule. A two carrier-type model was developed with an activation energy of $0.2 eV between the delta layer lowest subband with mobility$1 cm2/Vs and the bulk valence band with high mobility. This new understanding of the transport of holes in such boron delta-doped structures has shown that although Hall mobility as high as 900 cm2/Vs was measured at room temperature, this dramatically overstates the actual useful performance of the device

The brand, culture & stakeholder-based brand management phenomenon : an international Delphi study

Most recently in academic literature, over the past decade, it has been observed that the cultural approach to brand management represents a new school of thought. This has emerged from relational and community based brand perspectives: which chart the rising role, significance and influence in brand management of connected and savvy consumers. Furthermore, the researcher has identified that economic migrancy; the increase in multi-racial and multicultural relations, evident in childbirth; urbanism and urbanization; Globalization; conspicuous branded consumption; and Web2.0 continue to drive new methods and channels for information exchanges, collaboration and societal understanding. These in turn are shaping and changing the way in which branding, management and consumption are being understood and practiced. Brands have gravitated towards a position of offering individual and societal meaning. In doing so they have become cultural artefacts and language shapers. In tandem the conceptual argument for a brand being understood and used as a ‘human’ has grown in prominence. Collectively, these represent a global cultural phenomenon where the management of brands appears to be a cultural, diffused and self-defined practice. The purpose of this study was to examine this identified phenomenon in greater detail, from a brand management perspective. The aim was to investigate the nature of the relationship between culture and brands – to the benefit of brand managers. The method of qualitative investigation elicited iterated views from an international panel of academics and practitioners -­ in the form of a 16 month Expert Delphi Study. Through the Delphi process, they were encouraged to arrive at a consensus of opinions and understanding. Findings of this doctoral study suggest that culture and brands share strong relationship bonds, brought into existence by human desires. Equally, brands and culture both have the ability to influence each other. Furthermore, the successful management of brands requires a cultural approach, which mediates dynamic and complex networks of brand stakeholder relations. It was concluded that the understandings of brands, culture and management have to take into account: context, space and time – as porous boundaries of transience and transcendence. A new, grounded theoretical framework for brand management was developed - which took its inspiration from Aristotle’s Praedicamenta. In addition, alternative criteria for collecting and analysing biographical data were proposed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Efficacy of triclabendazole and albendazole against Fasciola spp. infection in cattle in Côte d'Ivoire: a randomised blinded trial

Triclabendazole is the anthelminthic of choice for the treatment of fascioliasis, however, it is not yet registered in many countries. Therefore, we investigated the efficacy of a single-dose of triclabendazole (12 mg/kg) or albendazole (15 mg/kg) against Fasciola spp. infection in cattle on farms in the northern part of Cote d'Ivoire in a randomized clinical trial. Faecal samples were obtained from 196 cattle, of which 155 (79.1%) were found positive for Fasciola spp. by the sedimentation technique. Cattle infected with Fasciola spp. were randomly allocated (3:3:1) to receive triclabendazole (n=66), albendazole (n=67) or left untreated to serve as control (n=22). Follow-up faecal samples were collected on days 21, 28, 90 and 188 post-treatment. No adverse events were observed as reported by the farmer in any of the treatment groups. The proportion of non-egg shedding cattle (PNES), assessed at day 21 (primary outcome), was significantly higher in cattle treated with triclabendazole (95.4%) compared to those receiving albendazole (70.3%; odds ratio [OR] 0.11, 95% confidence interval [CI] 0.03-0.39, p <0.001). The egg reduction rate (ERR) expressed as number of eggs per gram of faeces (epg), a secondary endpoint assessed at day 21 post-treatment, was significantly higher in the triclabendazole arm (arithmetic mean (AM) ERR=99.8%) than in the albendazole arm (AM ERR=92.2%), with a difference of 7.6%-points (95% CI: 0.9-14.5%-points, p=0.03). Reinfection rates at days 90 and 188 post-treatment (secondary endpoint) were lower in the triclabendazole arm (5.3% and 18.5%) compared to the albendazole arm (23.5% and 33.3%). This is the first report of efficacy of triclabendazole against Fasciola spp. in naturally infected cattle in Cote d'Ivoire. Our results confirm that triclabendazole is the most effective treatment of fascioliasis and therefore, should be considered for the control of livestock fascioliasis; if resources allow in combination with intermediate host snail control and raising farmers awareness of pasture and livestock management to avoid reinfection

Near-Infrared Accretion Signatures from the Circumbinary Planetary-Mass Companion Delorme 1 (ab)b

Accretion signatures from bound brown dwarf and protoplanetary companions provide evidence for ongoing planet formation, and accreting substellar objects have enabled new avenues to study the astrophysical mechanisms controlling the formation and accretion processes. Delorme 1 (AB)b, a ?1/430-45 Myr circumbinary planetary-mass companion, was recently discovered to exhibit strong Hα emission. This suggests ongoing accretion from a circumplanetary disk, somewhat surprising given canonical gas disk dispersal timescales of 5-10 Myr. Here, we present the first NIR detection of accretion from the companion in Paβ, Pa?3, and Br?3 emission lines from SOAR/TripleSpec 4.1, confirming and further informing its accreting nature. The companion shows strong line emission, with L line ≈ 1-6 × 10-8 L ? across lines and epochs, while the binary host system shows no NIR hydrogen line emission (L line \u3c 0.32-11 × 10-7 L ?). Observed NIR hydrogen line ratios are more consistent with a planetary accretion shock than with local line excitation models commonly used to interpret stellar magnetospheric accretion. Using planetary accretion shock models, we derive mass accretion rate estimates of Ṁpla?1/43 -4 × 10-8 M J yr-1, somewhat higher than expected under the standard star formation paradigm. Delorme 1 (AB)b\u27s high accretion rate is perhaps more consistent with formation via disk fragmentation. Delorme 1 (AB)b is the first protoplanet candidate with clear (signal-to-noise ratio ?1/45) NIR hydrogen line emission

Prevalence and distribution of livestock schistosomiasis and fascioliasis in Côte d'Ivoire: results from a cross-sectional survey

BACKGROUND: Schistosoma and Fasciola are zoonotic parasites of public health and veterinary importance. However, while the epidemiology of schistosomiasis in humans is well studied, little is known about fascioliasis and schistosomiasis in livestock in Cote d'Ivoire. This study aimed to determine the prevalence and the distribution of livestock schistosomiasis and fascioliasis across Cote d'Ivoire. In 2018, we conducted a cross-sectional survey in abattoirs and farms in 13 departments of Cote d'Ivoire. In abattoirs, the mesenteric veins and livers of slaughtered cattle, sheep and goats were examined for adult Schistosoma and Fasciola flukes. Faeces from live cattle, goats and sheep were collected and examined for Schistosoma and Fasciola eggs using a sedimentation technique. RESULTS: A total of 386 cattle, 174 goats and 151 sheep from abattoirs and 435 cattle, 22 goats and 176 sheep from farms were sampled. The observed prevalence of schistosomiasis was higher in slaughtered animals. Fascioliasis was more prevalent in farm animals. The prevalence of schistosomiasis in slaughtered cattle varied between 5.9% (95% confidence interval (CI): 0.7-19.7%) and 53.3% (95% CI: 37.9-68.3%) with the highest prevalence observed in Ouangolodougou in the North. Cattle from farms had a relatively low prevalence of schistosomiasis, with the highest prevalence found in Ouangolodougou (2.4%, 95% CI: 0.7-6.1%). The prevalence of fascioliasis varied considerably from one department to another, ranging from nil (95% CI: 0.0-18.5%) to 50.8% (95% CI: 43.4-58.2%), with the highest prevalence found in farm cattle in Dikodougou in the North. Sheep and goats had a lower prevalence of schistosomiasis and fascioliasis than cattle. In slaughtered animals, cattle aged 4 years and older were at highest risk for schistosomiasis (odds ratio (OR): 2.4; 95% CI: 1.0-5.6) and fascioliasis (OR: 2.1; 95% CI: 1.1-3.9). In farm animals, male cattle had higher odds of being infected with Schistosoma (OR: 4.3; 95% CI: 0.7-26.9) than females. CONCLUSIONS: Our study confirms that schistosomiasis and fascioliasis are endemic in livestock across Cote d'Ivoire. A strategic control programme should be considered, especially for cattle, including providing drinking water in troughs to reduce faecal contamination of water sources by cattle

"It's making contacts" : notions of social capital and implications for widening access to medical education

Acknowledgements Our thanks to the Medical Schools Council (MSC) of the UK for funding Study A; REACH Scotland for funding Study B; and Queen Mary University of London, and to the medical school applicants and students who gave their time to be interviewed. Our thanks also to Dr Sean Zhou and Dr Sally Curtis, and Manjul Medhi, for their help with data collection for studies A and B respectively. Our thanks also to Dr Lara Varpio, Uniformed Services University of the USA, for her advice and guidance on collating data sets and her comments on the draft manuscript.Peer reviewedPublisher PD

Paediatric and adolescent athletes in Switzerland: age-adapted proposals for pre-participation cardiovascular evaluation

High-level sports competition is popular among Swiss youth. Even though preparticipation evaluation for competitive athletes is widespread, screening strategies for diseases responsible for sudden death during sport are highly variable. Hence, we sought to develop age-specific preparticipation cardiovascular evaluation (PPCE) proposals for Swiss paediatric and adolescent athletes (under 18 years of age). We recommend that all athletes practising in a squad with a training load of at least 6 hours per week should undergo PPCE based on medical history and physical examination from the age of 12 years on. Prior to 12 years, individual judgement of athletic performance is required. We suggest the inclusion of a standard 12-lead electrocardiogram (ECG) evaluation for all post-pubertal athletes (or older than 15 years) with analysis in accordance with the International Criteria for ECG Interpretation in Athletes. Echocardiography should not be a first-line screening tool but rather serve for the investigation of abnormalities detected by the above strategies. We recommend regular follow-up examinations, even for those having normal history, physical examination and ECG findings. Athletes with an abnormal history (including family history), physical examination and/or ECG should be further investigated and pathological findings discussed with a paediatric cardiologist. Importantly, the recommendations provided in this document are not intended for use among patients with congenital heart disease who require individualised care according to current guidelines

Gorenstein homological algebra and universal coefficient theorems

We study criteria for a ring—or more generally, for a small category—to be Gorenstein and for a module over it to be of finite projective dimension. The goal is to unify the universal coefficient theorems found in the literature and to develop machinery for proving new ones. Among the universal coefficient theorems covered by our methods we find, besides all the classic examples, several exotic examples arising from the KK-theory of C*-algebras and also Neeman’s Brown–Adams representability theorem for compactly generated categories