Neurohumoral and ambulatory haemodynamic adaptations following isometric exercise training in unmedicated hypertensive patients

Objective: Hypertension remains the leading modifiable risk factor for cardiovascular disease (CVD). Isometric exercise training (IET) has been shown to be a useful non-pharmacological intervention for reducing resting blood pressure (BP). This study aimed to measure alterations in office BP, ambulatory BP, cardiac autonomic modulation and inflammatory and vascular biomarkers following a programme of IET in unmedicated hypertensive patients. Methods: Twenty-four unmedicated stage 1 hypertensive patients (age 43.8±7.3 years; height, 178.1±7 cm; weight 89.7±12.8 kg) were randomly assigned in a cross-over study design, to 4-weeks of home based IET and control period, separated by a 3-week washout period. Office and Ambulatory BP, cardiac autonomic modulation, and inflammatory and vascular biomarkers were recorded pre and post IET and control periods. Results: Clinic and 24-hour ambulatory BP significantly reduced following IET by 12.4/6.2 mmHg and 11.8/5.6 mmHg in systolic/diastolic BP, respectively (p<0.001 for both), compared to the control. The BP adaptations were associated with a significant (p=0.018) reduction in the average real variability of 24-hour ambulatory BP following IET, compared to control. Cardiac autonomic modulation improved by 11% (p<0.001), baroreceptor reflex sensitivity improved by 47% (p<0.001), and interleukin-6 and asymmetric dimethylarginine reduced by 10% (p=0.022) and 19% (p=0.023), respectively, which differed significantly to the control period. Conclusion: This is the first evidence of durable BP reduction and wider CVD risk benefits of IET in a relevant patient population. Our findings support the role of IET as a safe and viable therapeutic and preventative intervention in the treatment of HTN

Doping of inorganic materials in microreactors – preparation of Zn doped Fe₃O₄ nanoparticles

Microreactor systems are now used more and more for the continuous production of metal nanoparticles and metal oxide nanoparticles owing to the controllability of the particle size, an important property in many applications. Here, for the first time, we used microreactors to prepare metal oxide nanoparticles with controlled and varying metal stoichiometry. We prepared and characterised Zn-substituted Fe₃O₄ nanoparticles with linear increase of Zn content (ZnxFe₃−xO₄ with 0 ≤ x ≤ 0.48), which causes linear increases in properties such as the saturation magnetization, relative to pure Fe₃O₄. The methodology is simple and low cost and has great potential to be adapted to the targeted doping of a vast array of other inorganic materials, allowing greater control on the chemical stoichiometry for nanoparticles prepared in microreactors

Exercise training and resting blood pressure: a large-scale pairwise and network meta-analysis of randomised controlled trials

Objective: To perform a large-scale pairwise and network meta-analysis on the effects of all relevant exercise training modes on resting blood pressure to establish optimal antihypertensive exercise prescription practices. Design: Systematic review and network meta-analysis. Data sources: PubMed (Medline), the Cochrane library and Web of Science were systematically searched. Eligibility criteria: Randomised controlled trials published between 1990 and February 2023. All relevant work reporting reductions in systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) following an exercise intervention of ≥2 weeks, with an eligible non-intervention control group, were included. Results: 270 randomised controlled trials were ultimately included in the final analysis, with a pooled sample size of 15 827 participants. Pairwise analyses demonstrated significant reductions in resting SBP and DBP following aerobic exercise training (−4.49/–2.53 mm Hg, p<0.001), dynamic resistance training (–4.55/–3.04 mm Hg, p<0.001), combined training (–6.04/–2.54 mm Hg, p<0.001), high-intensity interval training (–4.08/–2.50 mm Hg, p<0.001) and isometric exercise training (–8.24/–4.00 mm Hg, p<0.001). As shown in the network meta-analysis, the rank order of effectiveness based on the surface under the cumulative ranking curve (SUCRA) values for SBP were isometric exercise training (SUCRA: 98.3%), combined training (75.7%), dynamic resistance training (46.1%), aerobic exercise training (40.5%) and high-intensity interval training (39.4%). Secondary network meta-analyses revealed isometric wall squat and running as the most effective submodes for reducing SBP (90.4%) and DBP (91.3%), respectively. Conclusion: Various exercise training modes improve resting blood pressure, particularly isometric exercise. The results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension

Elliptic curves of large rank and small conductor

For r=6,7,...,11 we find an elliptic curve E/Q of rank at least r and the smallest conductor known, improving on the previous records by factors ranging from 1.0136 (for r=6) to over 100 (for r=10 and r=11). We describe our search methods, and tabulate, for each r=5,6,...,11, the five curves of lowest conductor, and (except for r=11) also the five of lowest absolute discriminant, that we found.Comment: 16 pages, including tables and one .eps figure; to appear in the Proceedings of ANTS-6 (June 2004, Burlington, VT). Revised somewhat after comments by J.Silverman on the previous draft, and again to get the correct page break

A pilot randomised controlled trial of cognitive behavioural therapy for antenatal depression

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Few trials have evaluated the effectiveness of psychological treatment in improving depression by the end of pregnancy. This is the first pilot randomised controlled trial (RCT) of individual cognitive behavioural therapy (CBT) looking at treating depression by the end of pregnancy. Our aim was to assess the feasibility of delivering a CBT intervention modified for antenatal depression during pregnancy. METHODS: Women in North Bristol, UK between 8-18 weeks pregnant were recruited through routine contact with midwives and randomised to receive up to 12 sessions of individual CBT in addition to usual care or to continue with usual care only. Women were eligible for randomisation if they screened positive on a 3-question depression screen used routinely by midwives and met ICD-10 criteria for depression assessed using the clinical interview schedule - revised version (CIS-R). Two CBT therapists delivered the intervention. Follow-up was at 15 and 33 weeks post-randomisation when assessments of mental health were made using measures which included the CIS-R. RESULTS: Of the 50 women assessed for the trial, 36 met ICD-10 depression criteria and were randomised: 18 to the intervention and 18 to usual care. Thirteen of the 18 (72%) women who were allocated to receive the intervention completed 9 or more sessions of CBT before the end of pregnancy. Follow-up rates at 15 and 33 weeks post-randomisation were higher in the group who received the intervention (89% vs. 72% at 15 weeks and 89% vs. 61% at 33 weeks post-randomisation). At 15 weeks post-randomisation (the end of pregnancy), there were more women in the intervention group (11/16; 68.7%) who recovered (i.e. no longer met ICD-10 criteria for depression), than those receiving only usual care (5/13; 38.5%). CONCLUSIONS: This pilot trial shows the feasibility of conducting a large RCT to assess the effectiveness of CBT for treating antenatal depression before the end of pregnancy. The intervention could be delivered during the antenatal period and there was some evidence to suggest that it could be effective. TRIAL REGISTRATION: ISRCTN44902048

Elliptic Curves over Real Quadratic Fields are Modular

We prove that all elliptic curves defined over real quadratic fields are modular.Comment: 38 pages. Magma scripts available as ancillary files with this arXiv versio

A new foundational crisis in mathematics, is it really happening?

The article reconsiders the position of the foundations of mathematics after the discovery of HoTT. Discussion that this discovery has generated in the community of mathematicians, philosophers and computer scientists might indicate a new crisis in the foundation of mathematics. By examining the mathematical facts behind HoTT and their relation with the existing foundations, we conclude that the present crisis is not one. We reiterate a pluralist vision of the foundations of mathematics. The article contains a short survey of the mathematical and historical background needed to understand the main tenets of the foundational issues.Comment: Final versio

Personality difficulties and response to community-based psychological treatment for anxiety and depression

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordThe data that support the findings of this study are available from the Somerset Partnership NHS Foundation Trust IAPT service but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.Background: Previous research suggests that comorbid personality disorder may be associated with a less favourable treatment outcome for individuals with depression and anxiety disorder. However, little is known about whether personality difficulties are associated with treatment outcomes within Improving Access to Psychological Therapies (IAPT) services-the largest platform for treating depression and anxiety in England, UK. Secondary aims were to investigate i) whether individual personality difficulties are associated with treatment outcome and ii) whether findings are moderated by treatment type. Methods: The sample included 3,689 adults who accessed community-based psychological treatment (cognitive behavioural therapy, emotional skills training, or other psychological therapy) for depression and/or anxiety disorder. Associations between personality difficulties (assessed with the Standardised Assessment of Personality–Abbreviated Scale (SAPAS)) and treatment outcomes (recovery and reliable improvement in depression/anxiety symptom scores, assessed using questionnaire-based measures) were investigated using logistic/linear regression. Results: Personality difficulties were associated with a reduced likelihood of recovery (adjusted OR per unit increase on SAPAS: depression=0.87, 95%CI 0.84, 0.91; anxiety=0.86, 95%CI 0.82, 0.90) and reliable improvement (adjusted OR per unit increase on SAPAS: depression=0.88, 95%CI 0.84, 0.92; anxiety=0.85, 95%CI 0.82, 0.89).. Those with three or more difficulties were over 30% less likely to recover/reliably improve. 2 Limitations: Personality difficulties data were collected via self-report and were not available for all participants. Conclusion: Patients with personality difficulties have a less favourable response to psychological treatment for depression/anxiety disorder. If replicated, the findings highlight a major challenge to the way community-based psychological therapy services in England (IAPT services) are presently constituted

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials