Growth and Diversification of Doctoral Education in the United Kingdom

The chapter analyses the growth in numbers of doctoral students and doctoral degrees awarded in the United Kingdom in recent years and develops two arguments related to this growth. First, doctoral education and training no longer serve almost exclusively the reproduction of the academic profession but provide a highly qualified workforce for the knowledge-intensive sectors of society. Second, due to the growth in the numbers, motives and purposes for obtaining a doctoral degree have diversified leading to the development of new routes towards a doctorate and an expansion in the types of doctoral degree. The United Kingdom is probably the European country with the highest degree of diversity in terms of doctoral degree types, and the most important ones are briefly described in the chapter. This second part will also include a brief discussion of nonacademic labour markets for doctoral degree holders. A third part of the chapter will look at the extended policy field into which doctoral education and training have increasingly been embedded in recent years. Given the fact that doctoral degree holders are a valuable resource (e.g. in human capital terms) for various economic sectors of the knowledge society, their education and training is no longer considered to be exclusively an academic affair. Instead, it is increasingly managed at institutional level and guided by policy processes at national and – at least in Europe – at supranational level. The fourth and final part of the chapter will discuss the question of the growing divergence or growing convergence in doctoral education and training. It is assumed that, despite the growing diversity of pathways and doctoral degree types, there is also some convergence at play – at least at the European level – in so far as quality assurance, definitions of skills and qualifications as well as procedures for the examination and award of degrees are increasingly subject to standards, rules and regulations defined by the European network of quality assurance agencies. It remains to be seen whether the exit of the United Kingdom from the European Union will have an impact on, or even reverse, this trend

Germline CRISPR/Cas9-mediated gene editing prevents vision loss in a novel mousemodel of Aniridia.

Aniridia is a rare eye disorder, which is caused by mutations in the paired box 6 (PAX6) gene and results in vision loss due to the lack of a long-term vision-saving therapy. One potential approach to treating aniridia is targeted CRISPR-based genome editing. To enable the Pax6 small eye (Sey) mouse model of aniridia, which carries the same mutation found in patients, for preclinical testing of CRISPR-based therapeutic approaches, we endogenously tagged the Sey allele, allowing for the differential detection of protein from each allele. We optimized a correction strategy in vitro then tested it in vivo in the germline of our new mouse to validate the causality of the Sey mutation. The genomic manipulations were analyzed by PCR, as well as by Sanger and next-generation sequencing. The mice were studied by slit lamp imaging, immunohistochemistry, and western blot analyses. We successfully achieved both in vitro and in vivo germline correction of the Sey mutation, with the former resulting in an average 34.8% ± 4.6% SD correction, and the latter in restoration of 3xFLAG-tagged PAX6 expression and normal eyes. Hence, in this study we have created a novel mouse model for aniridia, demonstrated that germline correction of the Sey mutation alone rescues the mutant phenotype, and developed an allele-distinguishing CRISPR-based strategy for aniridia

Transcriptional profiling of endobronchial ultrasound guided lymph node samples aids diagnosis of mediastinal lymphadenopathy

Background: Endobronchial ultrasound (EBUS) guided biopsy is the mainstay for investigation of mediastinal lymphadenopathy for laboratory diagnosis of malignancy, sarcoidosis or tuberculosis. However, improved methods for discriminating between tuberculosis and sarcoidosis and excluding malignancy are still needed. We sought to evaluate the role of genome-wide transcriptional profiling to aid diagnostic processes in this setting. Methods: Mediastinal lymph node samples from 88 individuals were obtained by EBUS guided aspiration for investigation of mediastinal lymphadenopathy and subjected to transcriptional profiling in addition to conventional laboratory assessments. Computational strategies were employed to evaluate the potential for using the transcriptome to distinguish between diagnostic categories. Results: Molecular signatures associated with granulomas or neoplastic and metastatic processes were clearly discernible in granulomatous and malignant lymph node samples respectively. Support vector machine (SVM) learning using differentially expressed genes showed excellent sensitivity and specificity profiles in receiver operating characteristic curve analysis with area under curve values >0.9 for discriminating between granulomatous and non-granulomatous disease, tuberculosis and sarcoidosis, and between cancer and reactive lymphadenopathy. A two-step decision tree using SVM to distinguish granulomatous and non-granulomatous disease, then between tuberculosis and sarcoidosis in granulomatous cases and between cancer and reactive lymphadenopathy in non-granulomatous cases achieved >90% specificity for each diagnosis and afforded greater sensitivity than existing tests to detect tuberculosis and cancer. In some diagnostically ambiguous cases computational classification predicted granulomatous disease or cancer before pathological abnormalities were evident. Conclusions: Machine learning analysis of transcriptional profiling in mediastinal lymphadenopathy may significantly improve the clinical utility of EBUS guided biopsies

Quantification of atopy, lung function and airway hypersensitivity in adults

<p>Abstract</p> <p>Background</p> <p>Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).</p> <p>Objective</p> <p>To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.</p> <p>Methods</p> <p>FEV₁ and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.</p> <p>Results</p> <p>Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV₁ (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10^-8). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10^-8, cat p = 3.93 × 10^-10, dog p = 3.03 × 10^-15, grass p = 2.95 × 10^-9). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).</p> <p>Conclusions</p> <p>In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.</p

T-Branes and Monodromy

We introduce T-branes, or "triangular branes," which are novel non-abelian bound states of branes characterized by the condition that on some loci, their matrix of normal deformations, or Higgs field, is upper triangular. These configurations refine the notion of monodromic branes which have recently played a key role in F-theory phenomenology. We show how localized matter living on complex codimension one subspaces emerge, and explain how to compute their Yukawa couplings, which are localized in complex codimension two. Not only do T-branes clarify what is meant by brane monodromy, they also open up a vast array of new possibilities both for phenomenological constructions and for purely theoretical applications. We show that for a general T-brane, the eigenvalues of the Higgs field can fail to capture the spectrum of localized modes. In particular, this provides a method for evading some constraints on F-theory GUTs which have assumed that the spectral equation for the Higgs field completely determines a local model.Comment: 110 pages, 5 figure

Effects of habitat and land use on breeding season density of male Asian Houbara Chlamydotis macqueenii

Landscape-scale habitat and land-use influences on Asian Houbara Chlamydotis macqueenii (IUCN Vulnerable) remain unstudied, while estimating numbers of this cryptic, low-density, over-hunted species is challenging. In spring 2013, male houbara were recorded at 231 point counts, conducted twice, across a gradient of sheep density and shrub assemblages within 14,300 km² of the Kyzylkum Desert, Uzbekistan. Four sets of models related male abundance to: (1) vegetation structure (shrub height and substrate); (2) shrub assemblage; (3) shrub species composition (multidimensional scaling); (4) remote-sensed derived land-cover (GLOBCOVER, 4 variables). Each set also incorporated measures of landscape rugosity and sheep density. For each set, multi-model inference was applied to generalised linear mixed models of visit-specific counts that included important detectability covariates and point ID as a random effect. Vegetation structure received strongest support, followed by shrub species composition and shrub assemblage, with weakest support for the GLOBCOVER model set. Male houbara numbers were greater with lower mean shrub height, more gravel and flatter surfaces, but were unaffected by sheep density. Male density (mean 0.14 km-2, 95% CI, 0.12‒0.15) estimated by distance analysis differed substantially among shrub assemblages, being highest in vegetation dominated by Salsola rigida (0.22 [CI, 0.20‒0.25]), high in areas of S. arbuscula and Astragalus (0.14 [CI, 0.13‒0.16] and 0.15 [CI, 0.14‒0.17] respectively), lower (0.09 [CI, 0.08‒0.10]) in Artemisia and lowest (0.04 [CI, 0.04‒0.05]) in Calligonum. The study area was estimated to hold 1,824 males (CI: 1,645‒2,030). The spatial distribution of relative male houbara abundance, predicted from vegetation structure models, had the strongest correspondence with observed numbers in both model-calibration and the subsequent year’s data. We found no effect of pastoralism on male distribution but potential effects on nesting females are unknown. Density differences among shrub communities suggest extrapolation to estimate country- or range-wide population size must take account of vegetation composition

Saving for your future self: The role of imaginary experiences

Despite increased longevity, many people fail to save the funds necessary to support their retirement. In an attempt both to elucidate and remedy this failing, research exploring the “future-self continuity” hypothesis has revealed that temporal discounting is decreased and saving increased when connections between one’s current and future self are strengthened. Here, we explored the possibility that a basic component of mental imagery–spatial visual perspective–may be an important determinant of people’s decisions to spend now or save for the future. The results of two experiments supported this prediction. Rates of saving were enhanced when a distant-future event was generated from a third-person vs. first-person vantage point, an effect that was mediated by visual bodily awareness during mental imagery

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study

Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS. Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis. Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis. Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti- HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti- HHV-8 titers requires further, prospective study

Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population. Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. Design, setting, and participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021. Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up). Main outcomes and measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points). Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate. Conclusions and relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile.info:eu-repo/semantics/publishedVersio