Limit theorems for von Mises statistics of a measure preserving transformation

For a measure preserving transformation $T$ of a probability space $(X,\mathcal F,\mu)$ we investigate almost sure and distributional convergence of random variables of the form $$x \to \frac{1}{C_n} \sum_{i_1<n,...,i_d<n} f(T^{i_1}x,...,T^{i_d}x),\, n=1,2,...,$$ where $f$ (called the \emph{kernel}) is a function from $X^d$ to $\R$ and $C_1, C_2,...$ are appropriate normalizing constants. We observe that the above random variables are well defined and belong to $L_r(\mu)$ provided that the kernel is chosen from the projective tensor product $$L_p(X_1,\mathcal F_1, \mu_1) \otimes_{\pi}...\otimes_{\pi} L_p(X_d,\mathcal F_d, \mu_d)\subset L_p(\mu^d)$$ with $p=d\,r,\, r\ \in [1, \infty).$ We establish a form of the individual ergodic theorem for such sequences. Next, we give a martingale approximation argument to derive a central limit theorem in the non-degenerate case (in the sense of the classical Hoeffding's decomposition). Furthermore, for $d=2$ and a wide class of canonical kernels $f$ we also show that the convergence holds in distribution towards a quadratic form $\sum_{m=1}^{\infty} \lambda_m\eta^2_m$ in independent standard Gaussian variables $\eta_1, \eta_2,...$. Our results on the distributional convergence use a $T$--\,invariant filtration as a prerequisite and are derived from uni- and multivariate martingale approximations

Growth differentiation factor-11 causes neurotoxicity during ischemia in vitro

Age-related neuronal dysfunction can be overcome by circulating factors present inyoung blood. Growth differentiation factor-11 (GDF-11), a systemic factor that declineswith age, can reverse age-related dysfunction in brain, heart and skeletal muscle. Giventhat age increases susceptibility to stroke, we hypothesized that GDF-11 may be directlyprotective to neurons following ischemia. Primary cortical neurons were isolated fromE18 Wistar rat embryos and cultured for 7–10 days. Neurons were deprived of oxygenand glucose (OGD) to simulate ischemia. Neuronal death was assessed by lactatedehydrogenase, propidium iodide or CellToxTMgreen cytotoxicity assays. 40 ng/mLGDF-11 administration during 2 h OGD significantly increased neuronal death following24 h recovery. However, GDF-11 pre-treatment did not affect neuronal death during 2 hOGD. GDF-11 treatment during the 24 h recovery period after 2 h OGD also did notalter death. Real-time monitoring for 24 h revealed that by 2 h OGD, GDF-11 treatmenthad increased neuronal death which remained raised at 24 h. Co-treatment of 1µMSB431542 (ALK4/5/7 receptor inhibitor) with GDF-11 prevented GDF-11 neurotoxicityafter 2 h OGD and 24 h OGD. Transforming growth factor beta (TGFβ) did not increaseneuronal death to the same extent as GDF-11 following OGD. GDF-11 neurotoxicity wasalso exhibited following neuronal exposure to hydrogen peroxide. These results revealfor the first time that GDF-11 is neurotoxic to primary neurons in the acute phase ofsimulated stroke through primarily ALK4 receptor signaling

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees.

PURPOSE: Encouraging office workers to 'sit less and move more' encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. METHODS: Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for Intervention versus Comparison groups. RESULTS: A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. CONCLUSIONS: W@WS is a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on "sitting less and moving more"

Placental capillary pericytes release excess extracellular vesicles under hypoxic conditions inducing a pro-angiogenic profile in term pregnancy

Supplementary data available online at: https://www.sciencedirect.com/science/article/pii/S0006291X2300181X#appsec1Copyright © 2023 The Authors. Pericytes are multifunctional cells wrapped around capillary endothelia, essential for vascular health, development, and blood flow regulation, although their role in human placental chorionic villi has not been fully explored. The second half of normal pregnancy is characterized by a progressive decline in placental and fetal oxygen levels which, by term, comprises a substantial degree of hypoxia. We hypothesized this hypoxia would stimulate pericyte regulation of chorionic villous capillary function. This study's objective was to investigate the role of hypoxia on normal term placental pericytes (PLVP) and their signaling to endothelial cells. First, we confirmed fetoplacental hypoxia at term by a new analysis of umbilical arterial blood oxygen tension of 3,010 healthy singleton neonates sampled at caesarean section and before labor. We then measured the release of cytokines, chemokines, and small extracellular vesicles (PLVPsv), from PLVP cultured at 20%, 8% and 1% O2. As O2 levels decreased, secreted cytokines and chemokines [interleukin-6 (IL-6), interleukin-1α (IL-1α) and vascular endothelial growth factor (VEGF)], and small extracellular vesicle markers, (Alix, Syntenin and CD9) increased significantly in the culture supernatants. When primary human umbilical vein endothelial cells (HUVEC) were cultured with PLVPsv, polygon formation, number, and tube formation length was significantly increased compared to cells not treated with PLVPsv, indicating PLVPsv stimulated angiogenesis. We conclude that adding PLVPsv stimulates angiogenesis and vessel stabilization on neighboring endothelial cells in response to hypoxia in term pregnancy compared to no addition of PLVPsv. Our finding that PLVP can release angiogenic molecules via extracellular vesicles in response to hypoxia may apply to other organ systems.MRC Program Grant (MR/J003360/1); rad Sutherland is supported by the National Health and Medical Research Council of Australia (APP1137776)

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Socio-demographic, behavioural and cognitive correlates of work-related sitting time in German men and women

Background: Sitting time is ubiquitous for most adults in developed countries and is most prevalent in three domains: in the workplace, during transport and during leisure time. The correlates of prolonged sitting time in workplace settings are not well understood. Therefore, the aim of this study was to examine the gender-specific associations between the socio-demographic, behavioural and cognitive correlates of work-related sitting time. Methods: A cross-sectional sample of working German adults (n = 1515; 747 men; 43.5 ± 11.0 years) completed questionnaires regarding domain-specific sitting times and physical activity (PA) and answered statements concerning beliefs about sitting. To identify gender-specific correlates of work-related sitting time, we used a series of linear regressions. Results The overall median was 2 hours of work-related sitting time/day. Regression analyses showed for men (β = -.43) and for women (β = -.32) that work-related PA was negatively associated with work-related sitting time, but leisure-related PA was not a significant correlate. For women only, transport-related PA (β = -.07) was a negative correlate of work-related sitting time, suggesting increased sitting times during work with decreased PA in transport. Education and income levels were positively associated, and in women only, age (β = -.14) had a negative correlation with work-related sitting time. For both genders, TV-related sitting time was negatively associated with work-related sitting time. The only association with cognitive correlates was found in men for the belief ‘Sitting for long periods does not matter to me’ (β = .10) expressing a more positive attitude towards sitting with increasing sitting durations. Conclusions: The present findings show that in particular, higher educated men and women as well as young women are high-risk groups to target for reducing prolonged work-related sitting time. In addition, our findings propose considering increasing transport-related PA, especially in women, as well as promoting recreation-related PA in conjunction with efforts to reduce long work-related sitting times

Statins Disrupt CCR5 and RANTES Expression Levels in CD4(+) T Lymphocytes In Vitro and Preferentially Decrease Infection of R5 Versus X4 HIV-1

BACKGROUND: Statins have previously been shown to reduce the in vitro infection of human immunodeficiency virus type 1 (HIV-1) through modulation of Rho GTPase activity and lipid raft formation at the cell surface, as well as by disrupting LFA-1 incorporation into viral particles. PRINCIPLE FINDINGS: Here we demonstrate that treatment of an enriched CD4(+) lymphocyte population with lovastatin (Lov), mevastatin (Mev) and simvastatin (activated and non-activated, Sim(A) and Sim(N), respectively) can reduce the cell surface expression of the CC-chemokine receptor CCR5 (P<0.01 for Sim(A) and Lov). The lowered CCR5 expression was associated with down-regulation of CCR5 mRNA expression. The CC-chemokine RANTES protein and mRNA expression levels were slightly increased in CD4(+) enriched lymphocytes treated with statins. Both R5 and X4 HIV-1 were reduced for their infection of statin-treated cells; however, in cultures where statins were removed and where a decrease in CCR5 expression was observed, there was a preferential inhibition of infection with an R5 versus X4 virus. CONCLUSIONS: The results indicate that the modulation of CC-chemokine receptor (CCR5) and CC-chemokine (RANTES) expression levels should be considered as contributing to the anti-viral effects of statins, preferentially inhibiting R5 viruses. This observation, in combination with the immunomodulatory activity exerted by statins, suggests they may possess more potent anti-HIV-1 activity when applied during the early stages of infection or in lowering viral transmission. Alternatively, statin treatment could be considered as a way to modulate immune induction such as during vaccination protocols

7th SOSORT consensus paper: conservative treatment of idiopathic & Scheuermann's kyphosis

<p>Abstract</p> <p/> <p>Thoracic hyperkyphosis is a frequent problem and can impact greatly on patient's quality of life during adolescence. This condition can be idiopathic or secondary to Scheuermann disease, a disease disturbing vertebral growth. To date, there is no sound scientific data available on the management of this condition. Some studies discuss the effects of bracing, however no guidelines, protocols or indication's of treatment for this condition were found. The aim of this paper was to develop and verify the consensus on managing thoracic hyperkyphosis patients treated with braces and/or physiotherapy.</p> <p>Methods</p> <p>The Delphi process was utilised in four steps gradually modified according to the results of a set of recommendations: we involved the SOSORT Board twice, then all SOSORT members twice, with a Pre-Meeting Questionnaire (PMQ), and during a Consensus Session at the SOSORT Lyon Meeting with a Meeting Questionnaire (MQ).</p> <p>Results</p> <p>There was an unanimous agreement on the general efficacy of bracing and physiotherapy for this condition. Most experts suggested the use of 4-5 point bracing systems, however there was some controversy with regards to physiotherapeutic aims and modalities.</p> <p>Conclusion</p> <p>The SOSORT panel of experts suggest the use of rigid braces and physiotherapy to correct thoracic hyperkyphosis during adolescence. The evaluation of specific braces and physiotherapy techniques has been recommended.</p

Vascular clamping in liver surgery: physiology, indications and techniques

This article reviews the historical evolution of hepatic vascular clamping and their indications. The anatomic basis for partial and complete vascular clamping will be discussed, as will the rationales of continuous and intermittent vascular clamping