Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis

MicroRNAs (miRNA) are a novel class of small noncoding single-stranded RNA molecules that regulate gene expression. There is increasing evidence of their importance in polycystic ovary syndrome (PCOS). The objective was to determine if miRNA-93 and miRNA-223 are differentially expressed in the circulation of women with PCOS compared to age matched women. A case–control study comparing women with PCOS (n = 25) to age and weight matched controls (n = 24) without PCOS was performed. MiRNA-93 and miRNA-223 were determined by total RNA reverse transcription. Both miRNA-93 and miRNA-223 were significantly increased relative to the control group (p < 0.01, p = 0.029 respectively). In both groups there was no correlation of either miRNA-93 or miRNA-223 with insulin, HOMA-IR, HOMA-β or testosterone levels. The area under the receiver operator characteristic curve for miR-223 and miR-93 was 0.66 and 0.72 respectively, suggesting miR-93 is a more efficient biomarker than miR-223 for diagnosis of PCOS. The combination of the two miRNAs together, tested using multiple logistic regression analysis, did not improve the diagnostic potential. In conclusion, circulating miRNA-93 and miRNA-223 were higher in women with PCOS compared to age and weight matched controls independent of insulin resistance and testosterone levels, and miR-93 may represent a novel diagnostic biomarker for PCOS

On the Quantum Geometry of Multi-critical CDT

We discuss extensions of a recently introduced model of multi-critical CDT to higher multi-critical points. As in the case of pure CDT the continuum limit can be taken on the level of the action and the resulting continuum surface model is again described by a matrix model. The resolvent, a simple observable of the quantum geometry which is accessible from the matrix model is calculated for arbitrary multi-critical points. We go beyond the matrix model by determining the propagator using the peeling procedure which is used to extract the effective quantum Hamiltonian and the fractal dimension in agreement with earlier results by Ambjorn et al. With this at hand a string field theory formalism for multi-critical CDT is introduced and it is shown that the Dyson-Schwinger equations match the loop equations of the matrix model. We conclude by commenting on how to formally obtain the sum over topologies and a relation to stochastic quantisation.Comment: 15 pages, 2 figures, improved discussion, some new results regarding Hausdorff dimension, as publishe

Access to and adequacy of psychological services for adult patients in UK hospices: a national, cross-sectional survey

Abstract Background Providing psychological support to people living with terminal illness is a fundamental part of hospice care. Recent research on delivery of psychological services in hospices in the United Kingdom (UK) on a national level, including inequalities or variation in practice, is limited. A nationwide survey will highlight any differences in provision and in doing so help focus future research and inform best practice both within the UK, and internationally. The specific objectives of this survey are to (1) chart the types of psychological support available to adult patients in hospices in the UK in line with the National Institute for Health and Care Excellence model; (2) explore how services are organised; and (3) gather service perspectives on adequacy of care, and facilitators and barriers to appropriate practice. Methods A cross-sectional online survey emailed to adult hospices in the UK in November–December 2019. One staff member involved in the delivery and/or organisation of psychological support was invited to participate per hospice. Of 193 invited hospices, 116 took part. Results Sixteen percent rated their hospice psychological service as wholly adequate. The majority reported that services can access specialist professionals, but many relied on external referrals. Barriers to best practice included funding and staff capacity; facilitators included clear referral structures, audit and appropriate needs and outcome assessments. Conclusions Access to psychological professionals has improved since the last survey 15 years ago, but the majority of responders felt their overall service was not wholly adequate. Basic emotional support is largely felt to be sufficient, but our results indicate a need for improvements in access to more specialist care. Partnerships with external mental health services may be key. Our findings highlight core facilitators and barriers to providing good psychological care at the end of life that should be considered by services both within the UK and on an international level. </jats:sec

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose–response associations from the Prospective Physical Activity, Sitting and Sleep Consortium

Aims/hypothesis The aim of this study was to examine the dose–response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. Methods We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. Results We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] −0.14 [−0.25, −0.02]) and 5 min/day stair climbing (−0.14 [−0.24, −0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose–response associations for any activity type or standing. There was an inverse dose–response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose–response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. Conclusions/interpretation In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification

Associations between sedentary behaviour and physical activity in children and adolescents: a meta-analysis

Physical activity and sedentary behaviour are associated with metabolic and mental health during childhood and adolescence. Understanding the inter-relationships between these behaviours will help to inform intervention design. This systematic review and meta-analysis synthesized evidence from observational studies describing the association between sedentary behaviour and physical activity in young people (<18 years). English-language publications up to August 2013 were located through electronic and manual searches. Included studies presented statistical associations between at least one measure of sedentary behaviour and one measure of physical activity. One hundred sixty-three papers were included in the meta-analysis, from which data on 254 independent samples was extracted. In the summary meta-analytic model (k = 230), a small, but significant, negative association between sedentary behaviour and physical activity was observed (r = -0.108, 95% confidence interval [CI] = -0.128, -0.087). In moderator analyses, studies that recruited smaller samples (n < 100, r = -0.193, 95% CI = -0.276, -0.109) employed objective methods of measurement (objectively measured physical activity; r = -0.233, 95% CI = -0.330, -0.137) or were assessed to be of higher methodological quality (r = -0.176, 95% CI = -0.215, -0.138) reported stronger associations, although effect sizes remained small. The association between sedentary behaviour and physical activity in young people is negative, but small, suggesting that these behaviours do not directly displace one another

Halving Balls in Deterministic Linear Time

Let \D be a set of $n$ pairwise disjoint unit balls in $\R^d$ and $P$ the set of their center points. A hyperplane \Hy is an \emph{$m$-separator} for \D if each closed halfspace bounded by \Hy contains at least $m$ points from $P$. This generalizes the notion of halving hyperplanes, which correspond to $n/2$-separators. The analogous notion for point sets has been well studied. Separators have various applications, for instance, in divide-and-conquer schemes. In such a scheme any ball that is intersected by the separating hyperplane may still interact with both sides of the partition. Therefore it is desirable that the separating hyperplane intersects a small number of balls only. We present three deterministic algorithms to bisect or approximately bisect a given set of disjoint unit balls by a hyperplane: Firstly, we present a simple linear-time algorithm to construct an $\alpha n$-separator for balls in $\R^d$, for any $0<\alpha<1/2$, that intersects at most $cn^{(d-1)/d}$ balls, for some constant $c$ that depends on $d$ and $\alpha$. The number of intersected balls is best possible up to the constant $c$. Secondly, we present a near-linear time algorithm to construct an $(n/2-o(n))$-separator in $\R^d$ that intersects $o(n)$ balls. Finally, we give a linear-time algorithm to construct a halving line in $\R^2$ that intersects $O(n^{(5/6)+\epsilon})$ disks. Our results improve the runtime of a disk sliding algorithm by Bereg, Dumitrescu and Pach. In addition, our results improve and derandomize an algorithm to construct a space decomposition used by L{\"o}ffler and Mulzer to construct an onion (convex layer) decomposition for imprecise points (any point resides at an unknown location within a given disk)

Relationship between Yeast Polyribosomes and Upf Proteins Required for Nonsense mRNA Decay

In yeast, the accelerated rate of decay of nonsense mutant mRNAs, called nonsense-mediated mRNA decay, requires three proteins, Upf1p, Upf2p, and Upf3p. Single, double, and triple disruptions of the UPF genes had nearly identical effects on nonsense mRNA accumulation, suggesting that the encoded proteins function in a common pathway. We examined the distribution of epitope-tagged versions of Upf proteins by sucrose density gradient fractionation of soluble lysates and found that all three proteins co-distributed with 80 S ribosomal particles and polyribosomes. Treatment of ly-sates with RNase A caused a coincident collapse of polyribosomes and each Upf protein into frac-tions containing 80 S ribosomal particles, as expected for proteins that are associated with polyribosomes. Mutations in the cysteine-rich (zinc finger) and RNA helicase domains of Upf1p caused loss of function, but the mutant proteins remained polyribosome-associated. Density gradi-ent profiles for Upf1p were unchanged in the absence of Upf3p, and although similar, were modestly shifted to fractions lighter than those containing polyribosomes in the absence of Upf2p. Upf2p shifted toward heavier polyribosome fractions in the absence of Upf1p and into fractions containing 80 S particles and lighter fractions in the absence of Upf3p. Our results suggest that the association of Upf2p with polyribosomes typically found in a wild-type strain depends on the presence and opposing effects of Upf1p and Upf3p