Extracellular Matrix Mineralization Promotes E11/gp38 Glycoprotein Expression and Drives Osteocytic Differentiation

Osteocytes are terminally differentiated osteoblasts which reside in a mineralized extracellular matrix (ECM). The factors that regulate this differentiation process are unknown. We have investigated whether ECM mineralization could promote osteocyte formation. To do this we have utilised MLO-A5 pre-osteocyte-like cells and western blotting and comparative RT-PCR to examine whether the expression of osteocyte-selective markers is elevated concurrently with the onset of ECM mineralization. Secondly, if mineralization of the ECM is indeed a driver of osteocyte formation, we reasoned that impairment of ECM mineralization would result in a reversible inhibition of osteocyte formation. Supplementation of MLO-A5 cell cultures with ascorbic acid and phosphate promoted progressive ECM mineralization as well as temporally associated increases in expression of the osteocyte-selective markers, E11/gp38 glycoprotein and sclerostin. Consistent with a primary role for ECM mineralization in osteocyte formation, we also found that inhibition of ECM mineralization, by omitting phosphate or adding sodium pyrophosphate, a recognized inhibitor of hydroxyapatite formation, resulted in a 15-fold decrease in mineral deposition that was closely accompanied by lower expression of E11 and other osteocyte markers such as Dmp1, Cd44 and Sost whilst expression of osteoblast markers Ocn and Col1a increased. To rule out the possibility that such restriction of ECM mineralization may produce an irreversible modification in osteoblast behaviour to limit E11 expression and osteocytogenesis, we also measured the capacity of MLO-A5 cells to re-enter the osteocyte differentiation programme. We found that the mineralisation process was re-initiated and closely allied to increased expression of E11 protein after re-administration of phosphate or omission of sodium pyrophosphate, indicating an ECM mineralization-induced restoration in osteocyte formation. These results emphasise the importance of cell-ECM interactions in regulating osteoblast behaviour and, more importantly, suggest that ECM mineralization exerts pivotal control during terminal osteoblast differentiation and acquisition of the osteocyte phenotype

Results of cross-faculty 'capstone' assessments involving nursing and performing arts students

This article describes how ‘capstone’ assessments were created to provide two different student groups, nursing and performing arts students, with a lived experience of learning together about their own fields of practice. Capstone assessments combine ‘live’ human simulation with self‑reflection and peer review. A capstone assessment is the integration of a body of relatively fragmented knowledge and learning to form a unified whole and can be used as a transitional assessment and a bridging experience to connect knowledge between modules or courses. The capstone assessments involved two faculties and four modules, three nursing and one performing arts. Case studies were designed to represent real-life situations that students were likely to encounter during their careers, either playing a patient as an actor or performing a caring role as a nurse. Assessments for the capstone simulation were formative, and involved the students engaging in self-reflection and peer review. Videos were available to enhance the self-reflection and peer-review process. Evaluation was undertaken through verbal feedback during debrief, written feedback, video footage and nursing student and acting student peer review. The experience of capstone assessments for two diverse student groups provided valuable learning from their own and from a different group outside their subject area

Impact of co‐morbid personality disorder on quality of inpatient mental health services for people with anxiety and depression

Introduction Concerns have been raised about the quality of inpatient care received by patients with a diagnosis of personality disorder. Objectives The aim of this study was to examine the quality of care received by inpatients with an anxiety or depressive disorder, comparing subgroups with or without a co‐morbid personality disorder. Method We used a retrospective case‐note review of 3 795 patients admitted to inpatient psychiatric wards in England, utilizing data from the National Clinical Audit of Anxiety and Depression. Data were gathered on all acute admissions with an anxiety or depressive disorder over a 6‐month period, for a number of measures reflecting quality of care derived from national standards. Association of coexisting personality disorder with quality of care was investigated using multivariable regression analyses. Results Four hundred sixteen (11.0%) of the patients had a co‐co‐morbid diagnosis of personality disorder. Patients with personality disorder were less likely to have been asked about prior responses to treatment in their initial assessment (odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.50 to 0.89, p = 0.007). They were less likely to receive adequate notice in advance of their discharge (OR = 0.87, 95% CI 0.65 to 0.98, p = 0.046). They were more likely to be prescribed medication at the point of discharge (OR = 1.52, 95% CI 1.02 to 2.09, p = 0.012) and less likely to have been provided with information about the medicines they were taking (OR = 0.86, 95% CI 0.69 to 0.94, p = 0.048). In addition, the carers of patients with co‐morbid personality disorder were less likely to have been provided with information about available support services (OR = 0.73, 95% CI 0.51 to 0.93, p = 0.045). Conclusion We found evidence of poorer quality of care for patients with co‐morbid personality disorder who were admitted to psychiatric hospital for treatment of anxiety or depressive disorders, highlighting the need for improved clinical care in this patient group

Quality of English inpatient mental health services for people with anxiety or depressive disorders: Findings and recommendations from the core audit of the National Clinical Audit of Anxiety and Depression

Background Clinical audit is a sustained cyclical quality improvement process seeking to improve patient care and outcomes by evaluating services against explicit standards and implementing necessary changes. National audits aim to improve population-level clinical care by identifying unwarranted variations and making recommendations for clinicians, managers and service commissioners. The National Clinical Audit of Anxiety and Depression aimed to improve clinical care for people admitted to English hospitals for treatment of anxiety and depression, to provide comparative data on quality of care, and to support local quality improvement initiatives by identifying and sharing examples of best practice. Procedures Thirteen standards were developed based on NICE guidelines, literature review and feedback from a steering committee and reference group of service users and carers. All providers of NHS inpatient mental health services in England submitted details of between 20 and 100 service users/patients admitted between April 2017 and September 2018. To ascertain data reliability, participating services re-audited 5 sets of case-notes with a second auditor, and the coordinating team checked 10 randomly-selected sets of case-notes from 3 services, also selected at random. The reference group and steering committee identified key findings and developed a series of recommendations, which were discussed in regional quality improvement workshops and on-line webinars. Findings Data from 3795 case notes were analysed. A sizeable proportion of records indicated that at least one important aspect of initial assessment was not documented. Many service users/patients who could have benefited from an intervention targeted at optimising physical health did not receive it. Only a minority (39%) were referred for psychological therapy. Use of outcome measures varied considerably but no single outcome measure was being used routinely. Most individuals had a care plan recorded in the notes, but a review date was documented in only two-thirds, and almost half of individuals had not received a copy. Conclusions There was considerable variation between English mental health services across many variables, and much scope for improvement. Clinicians should ensure that care plans are developed collaboratively with service users/patients and identified carers should be provided with information about support services. Health services should investigate the reasons for low referral rates for psychological therapies. Clinicians should ensure all service users have jointly developed crisis plans in place at discharge. Service managers should agree outcome measures to evaluate the treatment provided and clinicians should use these measures at initial assessment and review appointments. The implementation of such changes provides an opportunity for collaborative research into mental health service delivery and quality

Re-thinking soil carbon modelling: a stochastic approach to quantify uncertainties

The benefits of sequestering carbon are many, including improved crop productivity, reductions in greenhouse gases, and financial gains through the sale of carbon credits. Achieving better understanding of the sequestration process has motivated many deterministic models of soil carbon dynamics, but none of these models addresses uncertainty in a comprehensive manner. Uncertainty arises in many ways - around the model inputs, parameters, and dynamics, and subsequently model predictions. In this paper, these uncertainties are addressed in concert by incorporating a physical-statistical model for carbon dynamics within a Bayesian hierarchical modelling framework. This comprehensive approach to accounting for uncertainty in soil carbon modelling has not been attempted previously. This paper demonstrates proof-of-concept based on a one-pool model and identifies requirements for extension to multi-pool carbon modelling. Our model is based on the soil carbon dynamics in Tarlee, South Australia. We specify the model conditionally through its parameters, soil carbon input and decay processes, and observations of those processes. We use a particle marginal Metropolis-Hastings approach specified using the LibBi modelling language. We highlight how samples from the posterior distribution can be used to summarise our knowledge about model parameters, to estimate the probabilities of sequestering carbon, and to forecast changes in carbon stocks under crop rotations not represented explicitly in the original field trials

Dynamics of Arctic Permafrost Coasts in the 21st Century

Climate warming is particularly pronounced in the Arctic with temperatures rising twice as much as in the rest of the world. It seems natural that this warming has profound effects on the speed of erosion of Arctic coasts, since the majority consists of permafrost, composed of unlithified material and hold together by ice. Permafrost stores approximately 1307 Gt of carbon, which is almost 60 % more than currently being contained in the atmosphere. Understanding the main drivers and dynamics of permafrost coastal erosion is of global relevance, especially since floods and erosion are both projected to intensify. However, the assessment of the impacts of climate warming on Arctic coasts is impaired by little data availability. We reviewed relevant scientific literature on changing dynamics of Arctic coast, potential drivers of these changes and the impacts on the human and natural environment. We provide a comprehensive overview over the state of the art and share our thoughts on how we envision potential pathways of future Arctic coastal research. We found that the overwhelming majority of all studied Arctic coasts is erosive and that in most cases erosion rates per year are increasing, threatening coastal settlements, infrastructure, cultural sites and archaeological remains. The impacts on the natural environment are also manifold and reach from changing sediment fluxes which limit light availability in the water column to a higher input of carbon and nutrients into the nearshore zone with the potential to influence food chains

Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

Statistical mechanics of voting

Decision procedures aggregating the preferences of multiple agents can produce cycles and hence outcomes which have been described heuristically as `chaotic'. We make this description precise by constructing an explicit dynamical system from the agents' preferences and a voting rule. The dynamics form a one dimensional statistical mechanics model; this suggests the use of the topological entropy to quantify the complexity of the system. We formulate natural political/social questions about the expected complexity of a voting rule and degree of cohesion/diversity among agents in terms of random matrix models---ensembles of statistical mechanics models---and compute quantitative answers in some representative cases.Comment: 9 pages, plain TeX, 2 PostScript figures included with epsf.tex (ignore the under/overfull \vbox error messages