Developing strategic learning alliances: partnerships for the provision of global education and training solutions

The paper describes a comprehensive model for the development of strategic alliances between education and corporate sectors, which is required to ensure effective provision of education and training programmes for a global market. Global economic forces, combined with recent advances in information and communication technologies, have provided unprecedented opportunities for education providers to broaden the provision of their programmes both on an international scale and across new sectors. Lifelong learning strategies are becoming increasingly recognized as an essential characteristic of a successful organization and therefore large organizations have shown a preparedness to invest in staff training and development. The demands for lifelong learning span a wide range of training and educational levels from school-level and vocational courses to graduate-level training for senior executive

Topical preparations for the treatment of psoriasis in primary care: a systematic review

Context: There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. Objective To assess the relative effectiveness and tolerability of topical treatments for psoriasis in primary care. Data sources: All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. Study selection: (1) Randomised placebo-controlled trials of topical treatments for psoriasis and (2) randomised head-to-head studies of the new vitamin D3 derivative treatments for psoriasis, that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Sensitivity Index or Investigator Assessment of Global Improvement. Data extraction: Eligibility and validity were assessed and data extracted independently by two authors. Data synthesis: Clinical outcomes were pooled using a random effect standardised weighted mean difference (SWMD) metric, including 3,380 patients randomised in 41 placebo (vehicle) controlled trials and 4,898 patients randomised in 28 head-to-head studies. There was a significant benefit in favour of active treatments against vehicle, SWMD: -1.06 (95%Cl: -1.26 to -0.86), approximately a 2-point improvement on a 12-point TSS after 6 to 8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids; SWMD: -1.51 (95%Cl: -1.76 to -1.25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0.42 (95%Cl: 0.12 to 0.72) approximately a 0.8 point improvement on a 12-point TSS> No important differences in withdrawal or reporting of adverse events were identified. Conclusions Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long-term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.psoriasis, treatment, chronic disease management

Mapping subnational HIV mortality in six Latin American countries with incomplete vital registration systems

Background: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods: We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results: All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions: Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths

A study to investigate the expression, structure and function of alternatively spliced progesterone receptor variants in breast cancer cells

The progesterone receptor (PR) gene consists of eight exons and encodes the functionally distinct PR-A and B isoforms. PR alternative splicing events involving deletion of internal exons or intron retention have been reported, potentially generating proteins which lack various internal functional domains or are N-terminally truncated. PR status in breast cancer may be predictive of the efficacy of endocrine therapy and is measured using N-terminally targeted antibodies which detect both PR-A and B. In this study PR mRNA expression was assessed in breast cancer (MCF-7, T47-D and MDA-MB-231) and non-tumourigenic breast (MCF-10A) cell lines using an RT-PCR based gene walking assay. PR mRNA resulting from alternative splicing was detected in reportedly PR negative MDA-MB-231 cells using this assay. These mRNA could encode the low molecular weight nuclear and cytoplasmic PR proteins which are detected in this cell line using the C-terminal PR antibody C19. Ligand blotting, co-immunoprecipitation and DNA affinity precipitation assays demonstrated the ability of these proteins to bind progesterone, interact with the PR nuclear co-factor PSF, dimerise and bind DNA; thus potentially to function as ligand activated nuclear transcription factors. Validation studies using the gene walking assay demonstrate that alternatively spliced PR mRNA was also present in breast tumours originally characterised using N-terminal antibodies as being both PR+ and PR-. Using a novel non N-terminal PR antibody developed in this study, the nuclear PR status differed from the original status for 2 of 14 tumours examined, and cytoplasmic PR was detected. The results presented in this thesis suggest that PR undergoes extensive alternative splicing, generating potentially functional isoforms, and that expression of variant PR isoforms may affect the PR status of a tumour as determined using antibodies targeting different epitopes. PR exons 4 and 6 are flanked by consensus 5′ and 3′ splice sites and contain cryptic 3′ splice sites, as well as potential binding sites for a range of RNA binding splicing factors. siRNA knockdown of the individual SR proteins SRSF1, SRSF2, SRSF5 and SRSF6 identified potentially antagonistic roles for SRSF1 and SRSF2 in influencing the inclusion/skipping of PR exons 4 and 6, and also for SRSF6 in regulating exon 6 splicing.EThOS - Electronic Theses Online ServiceRVI Breast Cancer AppealGBUnited Kingdo

Hemodynamic Effects of Entry and Exit Tear Size in Aortic Dissection Evaluated with In Vitro Magnetic Resonance Imaging and Fluid-Structure Interaction Simulation

Understanding the complex interplay between morphologic and hemodynamic features in aortic dissection is critical for risk stratification and for the development of individualized therapy. This work evaluates the effects of entry and exit tear size on the hemodynamics in type B aortic dissection by comparing fluid-structure interaction (FSI) simulations with in vitro 4D-flow magnetic resonance imaging (MRI). A baseline patient-specific 3D-printed model and two variants with modified tear size (smaller entry tear, smaller exit tear) were embedded into a flow- and pressure-controlled setup to perform MRI as well as 12-point catheter-based pressure measurements. The same models defined the wall and fluid domains for FSI simulations, for which boundary conditions were matched with measured data. Results showed exceptionally well matched complex flow patterns between 4D-flow MRI and FSI simulations. Compared to the baseline model, false lumen flow volume decreased with either a smaller entry tear (-17.8 and -18.5 %, for FSI simulation and 4D-flow MRI, respectively) or smaller exit tear (-16.0 and -17.3 %). True to false lumen pressure difference (initially 11.0 and 7.9 mmHg, for FSI simulation and catheter-based pressure measurements, respectively) increased with a smaller entry tear (28.9 and 14.6 mmHg), and became negative with a smaller exit tear (-20.6 and -13.2 mmHg). This work establishes quantitative and qualitative effects of entry or exit tear size on hemodynamics in aortic dissection, with particularly notable impact observed on FL pressurization. FSI simulations demonstrate acceptable qualitative and quantitative agreement with flow imaging, supporting its deployment in clinical studies.Comment: Judith Zimmermann and Kathrin B\"aumler contributed equall

Randomized, Controlled Trial Evaluating a Baby Wash Product on Skin Barrier Function in Healthy, Term Neonates

Objectives To examine the hypothesis that the use of a wash product formulated for newborn (<1 month of age) bathing is not inferior (no worse) to bathing with water only. Design Assessor‐blinded, randomized, controlled, noninferiority trial. Setting A teaching hospital in the Northwest of England and in participants’ homes. Participants Three‐hundred‐and‐seven healthy, term infants recruited within 48 hours of birth. Method We compared bathing with a wash product (n = 159) to bathing with water alone (n = 148). The primary outcome was transepidermal water loss (TEWL) at 14 days postbirth; the predefined difference deemed to be unimportant was 1.2. Secondary outcomes comprised changes in stratum corneum hydration, skin surface pH, clinical observations of the skin, and maternal views. Results Complete TEWL data were obtained for 242 (78.8%) infants. Wash was noninferior to water alone in terms of TEWL (intention‐to‐treat analysis: 95% confidence interval [CI] for difference [wash–water, adjusted for family history of eczema, neonate state, and baseline] −1.24, 1.07; per protocol analysis: 95% CI −1.42, 1.09). No significant differences were found in secondary outcomes. Conclusion We were unable to detect any differences between the newborn wash product and water. These findings provide reassurance to parents who choose to use the test newborn wash product or other technically equivalent cleansers and provide the evidence for health care professionals to support parental choice

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018

Publisher Copyright: © 2022, The Author(s).Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.Peer reviewe