How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?

In 2011, the James Lind Alliance published a ‘top 10’ list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long‐term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the ‘glucose variability hypothesis’. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross‐sectional, and based on ‘finger‐prick’ glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short‐term glucose variability on long‐term complications. Few other high‐quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA1c and avoidance of hypoglycaemia

How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?

In 2011, the James Lind Alliance published a ‘top 10’ list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long‐term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the ‘glucose variability hypothesis’. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross‐sectional, and based on ‘finger‐prick’ glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short‐term glucose variability on long‐term complications. Few other high‐quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA1c and avoidance of hypoglycaemia

The 3-D skills model: a randomised controlled pilot study comparing a novel 1–1 near-peer teaching model to a formative OSCE with self-regulated practice

Introduction: Near-peer teaching is a popular pedagogical teaching tool, with well-recognised benefits for students and tutors. There are multiple existing models to structure these interventions, but it is often unclear how they translate to academic attainment. We designed a novel near-peer teaching model that expands on previous research. Methods: Our model was piloted in a formative Objective Structured Clinical Examination (OSCE) setting, trialled on 22 pre-clinical medical students to establish feasibility, acceptability and descriptive outcomes that could inform the design of a larger study. Students were randomly assigned to intervention or control cohorts. Each cohort undertook 5 min formative OSCE assessments with either 3 additional minutes of structured teaching or 3 min of self-regulated practice before reattempting the first OSCE station. Checklist marking sheets for 1st and 2nd sittings were collected by independent external markers, in addition to a global assessment rating in which we used the Borderline Regression Method to establish the station pass mark. Results: A quantitative and qualitative result analysis was performed, demonstrating that students gained on average 3 additional marks after teaching with this model. Students and student-tutors reported increased confidence, high course satisfaction and evidence of reflective practice. Discussion: We established acceptability and feasibility outcomes. The descriptive outcomes will support the design of a larger, adequately powered study required to demonstrate translation to summative exam performance

Environmental Regulation Can Arise Under Minimal Assumptions

Models that demonstrate environmental regulation as a consequence of organism and environment coupling all require a number of core assumptions. Many previous models, such as Daisyworld, require that certain environment-altering traits have a selective advantage when those traits also contribute towards global regulation. We present a model that results in the regulation of a global environmental resource through niche construction without employing this and other common assumptions. There is no predetermined environmental optimum towards which regulation should proceed assumed or coded into the model. Nevertheless, polymorphic stable states that resist perturbation emerge from the simulated co-evolution of organisms and environment. In any single simulation a series of different stable states are realised, punctuated by rapid transitions. Regulation is achieved through two main subpopulations that are adapted to slightly different resource values, which force the environmental resource in opposing directions. This maintains the resource within a comparatively narrow band over a wide range of external perturbations. Population driven oscillations in the resource appear to be instrumental in protecting the regulation against mutations that would otherwise destroy it. Sensitivity analysis shows that the regulation is robust to mutation and to a wide range of parameter settings. Given the minimal assumptions employed, the results could reveal a mechanism capable of environmental regulation through the by-products of organisms

Phantom Field with O(N) Symmetry in Exponential Potential

In this paper, we study the phase space of phantom model with O(\emph{N}) symmetry in exponential potential. Different from the model without O(\emph{N}) symmetry, the introduction of the symmetry leads to a lower bound $w>-3$ on the equation of state for the existence of stable phantom dominated attractor phase. The reconstruction relation between the potential of O(\textit{N}) phantom system and red shift has been derived.Comment: 5 pages, 3 figures, replaced with the version to appear on Phys. Rev.

Viva la VOSCE

Background The COVID-19 pandemic lockdown precluded face-to-face final Objective Structured Clinical Examinations (OSCE) in the UK. Results In response, we rapidly developed and then successfully implemented a novel Virtual Objective Structured Clinical Examination (VOSCE). Conclusions In this article we both describe and reflect on our experience as well as discuss the implications for future undergraduate assessment as the situation evolves

Holographic Dark Energy and the Universe Expansion Acceleration

By incorporating the holographic principle in a time-depending Lambda-term cosmology, new physical bounds on the arbitrary parameters of the model can be obtained. Considering then the dark energy as a purely geometric entity, for which no equation of state has to be introduced, it is shown that the resulting range of allowed values for the parameters may explain both the coincidence problem and the universe accelerated expansion, without resorting to any kind of additional structures.Comment: Ordinary LaTex, 8 page

Transverse Spin at PHENIX: Results and Prospects

The Relativistic Heavy Ion Collider (RHIC), as the world's first and only polarized proton collider, offers a unique environment in which to study the spin structure of the proton. In order to study the proton's transverse spin structure, the PHENIX experiment at RHIC took data with transversely polarized beams in 2001-02 and 2005, and it has plans for further running with transverse polarization in 2006 and beyond. Results from early running as well as prospective measurements for the future will be discussed.Comment: 6 pages, 2 figures, presented at Transversity 2005, Como, Ital

Ultra-High Energy Neutrino Fluxes and Their Constraints

Applying our recently developed propagation code we review extragalactic neutrino fluxes above 10^{14} eV in various scenarios and how they are constrained by current data. We specifically identify scenarios in which the cosmogenic neutrino flux, produced by pion production of ultra high energy cosmic rays outside their sources, is considerably higher than the "Waxman-Bahcall bound". This is easy to achieve for sources with hard injection spectra and luminosities that were higher in the past. Such fluxes would significantly increase the chances to detect ultra-high energy neutrinos with experiments currently under construction or in the proposal stage.Comment: 11 pages, 15 figures, version published in Phys.Rev.

Cells and gene expression programs in the adult human heart

Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease