Cartilage on the Move: Cartilage Lineage Tracing During Tadpole Metamorphosis

The reorganization of cranial cartilages during tadpole metamorphosis is a set of complex processes. The fates of larval cartilage-forming cells (chondrocytes) and sources of adult chondrocytes are largely unknown. Individual larval cranial cartilages may either degenerate or remodel, while many adult cartilages appear to form de novo during metamorphosis. Determining the extent to which adult chondrocytes/cartilages are derived from larval chondrocytes during metamorphosis requires new techniques in chondrocyte lineage tracing. We have developed two transgenic systems to label cartilage cells throughout the body with fluorescent proteins. One system strongly labels early tadpole cartilages only. The other system inducibly labels forming cartilages at any developmental stage. We examined cartilages of the skull (viscero- and neurocranium), and identified larval cartilages that either resorb or remodel into adult cartilages. Our data show that the adult otic capsules, tecti anterius and posterius, hyale, and portions of Meckel\u27s cartilage are derived from larval chondrocytes. Our data also suggest that most adult cartilages form de novo, though we cannot rule out the potential for extreme larval chondrocyte proliferation or de- and re-differentiation, which could dilute our fluorescent protein signal. The transgenic lineage tracing strategies developed here are the first examples of inducible, skeleton-specific, lineage tracing in Xenopus

Using learning design as a framework for supporting the design and reuse of OER

The paper will argue that adopting a learning design methodology may provide a vehicle for enabling better design and reuse of Open Educational Resources (OERs). It will describe a learning design methodology, which is being developed and implemented at the Open University in the UK. The aim is to develop a 'pick and mix' learning design toolbox of different resources and tools to help designers/teachers make informed decisions about creating new or adapting existing learning activities. The methodology is applicable for designers/teachers designing in a traditional context – such as creation of materials as part of a formal curriculum, but also has value for those wanting to create OERs or adapt and repurpose existing OERs. With the increasing range of OERs now available through initiatives as part of the Open Courseware movement, we believe that methodologies, such as the one we describe in this paper, which can help guide reuse and adaptation will become increasingly important and arguably are an important aspect of ensuring longer term sustainability and uptake of OERs. Our approach adopts an empirically based approach to understanding and representing the design process. This includes a range of evaluation studies (capturing of case studies, interviews with designers/teachers, in-depth course evaluation and focus groups/workshops), which are helping to develop our understanding of how designers/teachers go about creating new learning activities. Alongside this we are collating an extensive set of tools and resources to support the design process, as well as developing a new Learning Design tool that helps teachers articulate and represent their design ideas. The paper will describe how we have adapted a mind mapping and argumentation tool, Compendium, for this purpose and how it is being used to help designers and teachers create and share learning activities. It will consider how initial evaluation of the use of the tool for learning design has been positive; users report that the tool is easy to use and helps them organise and articulate their learning designs. Importantly the tool also enables them to share and discuss their thinking about the design process. However it is also clear that visualising the design process is only one aspect of design, which is complex and multi-faceted

‘They’re more like ordinary stroppy British women’: Attitudes and expectations of maternity care professionals to UK-born ethnic minority women

Objective To explore the attitudes and expectations of maternity care professionals to UK-born ethnic minority mothers. Methods Qualitative in-depth interviews with 30 professionals from eight NHS maternity units in England that provide services for large proportions of women of black Caribbean, black African, Indian, Pakistani and Irish descent. Results All the professionals reported providing care to both UK-born and migrant mothers from ethnic minorities. Most of them felt that they could differentiate between UK-born and migrant mothers based mainly on language fluency and accent. ‘Westernized dress’ and ‘freedom’ were also cited as indicators. Overall, professionals found it easier to provide services to UK-born mothers and felt that their needs were more like those of white English mothers than those of migrant mothers. UK-born mothers were generally thought to be assertive and expressive, and in control of care-related decision-making whereas some South Asian Muslim women were thought to be constrained by family influences. Preconceived ideas about ethnic minority mothers' tolerance of pain in labour, use of pharmacological pain relief measures and mode of delivery were recurring themes. Women's education and social class were felt to be major influences on the uptake of maternity care, regardless of ethnicity. Conclusions Professionals appeared to equate the needs of UK-born ethnic minority women with those of white English women. Overall, this has positive implications for care provision. Despite this, specific behavioural expectations and unconscious stereotypical views were evident and have the potential to affect clinical practice

Implementation of sit-stand desks as a workplace health initiative: stakeholder views"

Purpose Prolonged workplace sitting can harm employee health. Sit-stand desks are a potential workplace health initiative that might reduce and break up the time office-based employees spend sitting in the workplace. However, little is known about the feasibility and acceptability of providing sit-stand desks. The paper aims to discuss this issue. Design/methodology/approach The present study sought stakeholder employee views surrounding sit-stand desk implementation within two UK-based non-profit organisations with open-plan offices. This paper draws on qualitative semi-structured interviews with 26 stakeholder employees and 65 days of participant observations. Data were analysed using thematic analysis, and organisational cultural theory framed the study. Findings Stakeholders employees’ positioning of sit-stand desks as a workplace health initiative reflected their perceptions of the relationship between sit-stand desk provision, employee health and organisational effectiveness. Perceptions were shaped by the nature and context of the organisation and by occupation-specific processes. Relatively fixed (e.g. organisational structure) and modifiable (e.g. selecting products compatible with the environment) factors were found to restrict and facilitate the perceived feasibility of implementing sit-stand desks. Practical implications The findings offer several recommendations for workplaces to improve stakeholder employee attitudes towards sit-stand desk provision and to increase the ease and efficiency of implementation. Originality/value Whilst extant literature has tended to examine hypothetical views related to sit-stand desk provision, this study consulted relevant stakeholders following, and regarding, the sit-stand desk implementation process

Testing Protein Leverage in Lean Humans: A Randomised Controlled Experimental Study

A significant contributor to the rising rates of human obesity is an increase in energy intake. The ‘protein leverage hypothesis’ proposes that a dominant appetite for protein in conjunction with a decline in the ratio of protein to fat and carbohydrate in the diet drives excess energy intake and could therefore promote the development of obesity. Our aim was to test the ‘protein leverage hypothesis’ in lean humans by disguising the macronutrient composition of foods offered to subjects under ad libitum feeding conditions. Energy intakes and hunger ratings were measured for 22 lean subjects studied over three 4-day periods of in-house dietary manipulation. Subjects were restricted to fixed menus in random order comprising 28 foods designed to be similar in palatability, availability, variety and sensory quality and providing 10%, 15% or 25% energy as protein. Nutrient and energy intake was calculated as the product of the amount of each food eaten and its composition. Lowering the percent protein of the diet from 15% to 10% resulted in higher (+12±4.5%, p = 0.02) total energy intake, predominantly from savoury-flavoured foods available between meals. This increased energy intake was not sufficient to maintain protein intake constant, indicating that protein leverage is incomplete. Urinary urea on the 10% and 15% protein diets did not differ statistically, nor did they differ from habitual values prior to the study. In contrast, increasing protein from 15% to 25% did not alter energy intake. On the fourth day of the trial, however, there was a greater increase in the hunger score between 1–2 h after the 10% protein breakfast versus the 25% protein breakfast (1.6±0.4 vs 25%: 0.5±0.3, p = 0.005). In our study population a change in the nutritional environment that dilutes dietary protein with carbohydrate and fat promotes overconsumption, enhancing the risk for potential weight gain

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Contribution of chromosomal polymorphisms to the G-matrix of Mimulus guttatus

This is the peer reviewed version of the following article: Scoville, A., Lee, Y. W., Willis, J. H., & Kelly, J. K. (2009). Contribution of chromosomal polymorphisms to the G-matrix of Mimulus guttatus. The New Phytologist, 183(3), 803–815. http://doi.org/10.1111/j.1469-8137.2009.02947.x, which has been published in final form at http://doi.org/10.1111/j.1469-8137.2009.02947.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Evolution of genetic (co)variances (the G-matrix) fundamentally influences multitrait divergence. Here, we isolated the contribution of two chromosomal quantitative trait loci (QTLs), a meiotic drive locus and a polymorphic inversion, to the overall G-matrix for a suite of floral, phenological and male fitness traits in a population of Mimulus guttatus. This allowed us to predict the evolution of trait means and genetic (co)variances as a function of allele frequencies, and to evaluate theories about the maintenance of genetic variation in fitness. Individuals generated using a replicated F2 breeding design were grown under common conditions, genotyped and measured for trait values. Significant additive genetic variance existed for all traits, and most genetic covariances were significantly nonzero. Both QTLs contribute to the additive genetic (co)variances of multiple traits. Pleiotropy was not generally consistent, either between QTLs or with the genetic background. Shifts in allele frequencies at either QTL are predicted to result in substantial changes in the G-matrix. Both QTLs contribute substantially to the genetic variation in pollen viability. The Drive QTL, and perhaps also the inversion, demonstrates the contribution of balancing selection to the maintenance of genetic variation in fitness

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer

BACKGROUND: The role of image-guided surveillance as compared with planned neck dissection in the treatment of patients with squamous-cell carcinoma of the head and neck who have advanced nodal disease (stage N2 or N3) and who have received chemoradiotherapy for primary treatment is a matter of debate. METHODS: In this prospective, randomized, controlled trial, we assessed the noninferiority of positron-emission tomography–computed tomography (PET-CT)–guided surveillance (performed 12 weeks after the end of chemoradiotherapy, with neck dissection performed only if PET-CT showed an incomplete or equivocal response) to planned neck dissection in patients with stage N2 or N3 disease. The primary end point was overall survival. RESULTS: From 2007 through 2012, we recruited 564 patients (282 patients in the planned-surgery group and 282 patients in the surveillance group) from 37 centers in the United Kingdom. Among these patients, 17% had nodal stage N2a disease and 61% had stage N2b disease. A total of 84% of the patients had oropharyngeal cancer, and 75% had tumor specimens that stained positive for the p16 protein, an indicator that human papillomavirus had a role in the causation of the cancer. The median follow-up was 36 months. PET-CT–guided surveillance resulted in fewer neck dissections than did planned dissection surgery (54 vs. 221); rates of surgical complications were similar in the two groups (42% and 38%, respectively). The 2-year overall survival rate was 84.9% (95% confidence interval [CI], 80.7 to 89.1) in the surveillance group and 81.5% (95% CI, 76.9 to 86.3) in the planned-surgery group. The hazard ratio for death slightly favored PET-CT–guided surveillance and indicated noninferiority (upper boundary of the 95% CI for the hazard ratio, <1.50; P=0.004). There was no significant difference between the groups with respect to p16 expression. Quality of life was similar in the two groups. PET-CT–guided surveillance, as compared with neck dissection, resulted in savings of £1,492 (approximately $2,190 in U.S. dollars) per person over the duration of the trial. CONCLUSIONS: Survival was similar among patients who underwent PET-CT–guided surveillance and those who underwent planned neck dissection, but surveillance resulted in considerably fewer operations and it was more cost-effective. (Funded by the National Institute for Health Research Health Technology Assessment Programme and Cancer Research UK; PET-NECK Current Controlled Trials number, ISRCTN13735240.