Quadrisecants give new lower bounds for the ropelength of a knot

Using the existence of a special quadrisecant line, we show the ropelength of any nontrivial knot is at least 15.66. This improves the previously known lower bound of 12. Numerical experiments have found a trefoil with ropelength less than 16.372, so our new bounds are quite sharp.Comment: v3 is the version published by Geometry & Topology on 25 February 200

Automated psychological therapy using immersive virtual reality for treatment of fear of heights: A single-blind, parallel-group, randomised controlled trial

Background Engaging, interactive, and automated virtual reality (VR) treatments might help solve the unmet needs of individuals with mental health disorders. We tested the efficacy of an automated cognitive intervention for fear of heights guided by an avatar virtual coach (animated using motion and voice capture of an actor) in VR and delivered with the latest consumer equipment. Methods We did a randomised trial of automated VR versus usual care. We recruited adults aged older than 18 years with a fear of heights by radio advertisements in Oxfordshire, UK. We diagnosed fear of heights if participants scored more than 29 on the Heights Interpretation Questionnaire (HIQ). We randomly allocated participants by computer in a 1:1 ratio to either automated VR delivered in roughly six 30-min sessions administered about two to three times a week over a 2-week period (intervention group) or to usual care (control group). Randomisation was stratified by severity of fear of heights. The research team, who were unaware of the random allocation, administered three fear-of-height assessments, at baseline (0 weeks), at the end of treatment (2 weeks), and at follow-up (4 weeks). The primary outcome measure was HIQ score (range 16–80, with higher scores indicating greater severity). This trial is registered with the ISRCTN registry, number ISRCTN11898283. Findings Between Nov 25, 2017, and Feb 27, 2018, 100 individuals were enrolled and underwent randomisation, of whom 49 were assigned to the VR treatment group and 51 to the control group. All participants completed the 4-week follow-up. The mean total treatment time in VR was 124·43 min (SD 34·23). Compared with participants in the control group, the VR treatment reduced fear of heights at the end of treatment (mean change score −24·5 [SD 13·1] in the VR group vs −1·2 [7·3] in the control group; adjusted difference −24·0, 95% CI −27·7 to −20·3; Cohen's d=2·0; p<0·0001). The benefit was maintained at follow-up (mean change score −25·1 [SD 13·9] in the VR group vs −1·5 [7·8] in the control group; adjusted difference −24·3, 95% CI −27·9 to −20·6; Cohen's d=2·0; p<0·0001). The number needed to treat to at least halve the fear of heights was 1·3. No adverse events were reported. Interpretation Psychological therapy delivered automatically by a VR coach can produce large clinical benefits. Evidence-based VR treatments have the potential to greatly increase treatment provision for mental health disorders

Time course of the interaction between tadalafil and nitrates

AbstractObjectivesThis study was designed to determine the time course of nitrate interaction with tadalafil, a phosphodiesterase 5 (PDE5) inhibitor with a half-life (t1/2) of 17.5 h.BackgroundThe PDE5 inhibitors augment the blood pressure (BP)-lowering effects of nitrates, yet the time course of this interaction is unclear. Recent guidelines from the American College of Cardiology/American Heart Association recommend that nitrates be withheld for 24 h after taking sildenafil (t1/2= 4 h).MethodsMale subjects (n = 150) received seven consecutive daily doses of placebo or tadalafil (20 mg). On day 7 and beyond, subjects received repeated doses of sublingual nitroglycerin (0.4 mg) after the last dose of placebo or tadalafil. After a 10- to 21-day washout period, subjects crossed over to either placebo or tadalafil, and nitrate dosing was repeated.ResultsIn response to nitroglycerin at 4, 8, and 24 h, standing systolic BP fell below 85 mm Hg in more subjects on tadalafil compared with placebo (p < 0.05), with no difference in the response to nitroglycerin at 48, 72, and 96 h (p > 0.2). Similar observations were made for standing diastolic BP <45 mm Hg, decrease in systolic BP >30 mm Hg, and decrease in diastolic BP >20 mm Hg. Nitroglycerin also evoked greater mean maximal decreases in standing systolic BP at 8 and 24 h after taking tadalafil versus placebo (p < 0.02), with no significant difference at 48, 72, or 96 h (p > 0.49).ConclusionsThe hemodynamic interaction between tadalafil and sublingual nitroglycerin lasted 24 h, but was not seen at 48 h and beyond. Similar to other PDE5 inhibitors, tadalafil should not be administered in combination with organic nitrates

Secondary data analysis of social care records to examine the provision of mental health support for young people in care

Background: Young people in care are much more likely to experience mental health difficulties than the general population, yet little is known about the provision of mental health support for this group in the United Kingdom. Methods: Using routinely collected social care data, we explored the provision of mental health support for 112 young people in care in the UK. We identified young people experiencing elevated internalising or externalising difficulties in their first year in care (based on strengths and difficulties questionnaire scores) and extracted data on mental health referrals and provision. We generated descriptive statistics relating to provision of mental health support and used regressions to examine predictors of mental health provision, and associations between support and mental health outcomes one and 2 years later. Results: Eighty-one percent of the children (n = 79) were referred to mental health services in their first year of being in care. Referrals were usually for emotional or conduct problems. Those with higher externalising symptoms were more likely to be referred than those with higher internalising symptoms (OR = 1.2, (95% confidence interval (CI): 1.01, 1.38)). Females were more likely to access support than males (OR = 3.82 (95% CI: 1.2, 13.3)). Sixty-eight percent of children (n = 66) accessed mental health services in their first year of being in care. Of those who accessed services, support ended prematurely for 29 (44%) of them, often due to placement instability or disengagement. Accessing support in the first year of care was not associated with changes in mental health 1 year (OR: 2.14 (95% CI: 0.62,7.29)), or 2 years after entering care (OR: 0.72–8.57, (95% CI: 0.72, 8.57)), although methodological limitations are noted. Conclusions: Mental health difficulties for children in care are recognised quickly, but mental health support may be difficult to access, with issues evident in retention and engagement

Interventions addressing challenging behaviours in Arab children and adults with intellectual disabilities and/or autism : a systematic review

Background: Arabs with intellectual disabilities and/or autism may exhibit challenging behaviour that affects them and their caregivers. Early, appropriate intervention may reduce these effects. This review synthesised and critically appraised challenging behaviour intervention research for this population. Methods: All published empirical research on challenging behaviour interventions for Arabs with intellectual disabilities and/or autism was included. In September 2022, 15 English and Arabic databases yielded 5,282 search records. Studies were appraised using the MMAT. Review findings were narratively synthesised. Results: The 79 included studies (n= 1,243 participants) varied in design, intervention, and evaluation method. Only 12.6% of interventions were well-designed and reported. Arab interventions primarily targeted children, were applied collectively on small samples, lacked individualised assessment, and were based on an inconsistent understanding of challenging behaviour. Conclusion: The evidence base on interventions for Arabs with intellectual disabilities and/or autism and challenging behaviour needs strengthening. Attention should be given to culturally relevant adaptations

Pharmacotherapy and pregnancy: Highlights from the first International Conference for Individualized Pharmacotherapy in Pregnancy

Data are sparse on the effects of medication use during pregnancy. Half of the world's population is women. The majority of women become pregnant, and many of those women take some kind of medication during their pregnancy, even if only for a short time. The majority of drugs have not been rigorously studied in pregnant women to determine the most effective dose with the least potential for adverse effects. Instead, women are given “cookie‐cutter” therapy, using doses extrapolated from nonpregnant women, men, or pregnant animals. This can lead to problems. Instead, individualization of pharmacotherapy in pregnancy promises to take individual women and determine the optimal dose and drug for them to maximize the effect of the drug while attempting to minimize the side effects to them and their unborn babies. Because this field of study is underrepresented, we held a conference to bring together researchers and experts to discuss current knowledge, issues, and challenges surrounding individualized pharmacotherapy in pregnancy. Speakers came from the NIH, the Food and Drug Administration (FDA), and various research centers in the United States and Canada. Below are the summaries of the discussions at the conference. Full notes from the panel discussions are available from the authors on request

Benthic foraminifera living in Gulf of Mexico bathyal and abyssal sediments : community analysis and comparison to metazoan meiofaunal biomass and density

Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 55 (2008): 2617-2626, doi:10.1016/j.dsr2.2008.07.011.Benthic foraminiferal biomass, density, and species composition were determined at ten sites in the Gulf of Mexico. During June 2001 and June 2002, sediment samples were collected with a GoMex boxcorer. A 7.5-cm diameter subcore was taken from a box core collected at each site and sliced into 1-cm or 2-cm sections to a depth of 2 or 3 cm; the >63-mm fraction was examined shipboard for benthic foraminifera. Individual foraminifers were extracted for adenosine triphosphate (ATP) using a luciferin-luciferase assay, which indicated the total ATP content per specimen; that data was converted to organic carbon. Foraminiferal biomass and density varied substantially (~2-53 mg C m-2; ~3,600-44,500 individuals m-2, respectively) and inconsistently with water depth. For example, although two ~1000-m deep sites were geographically separated by only ~75 km, the foraminiferal biomass at one site was relatively low (~9 mg C m-2) while the other site had the highest foraminiferal biomass (~53 mg C m-2). Although most samples from Sigsbee Plain (>3000 m) had low biomass, one Sigsbee site had >20 mg foraminiferal C m-2. The foraminiferal community from all sites (i.e., bathyal and abyssal locales) was dominated by agglutinated, rather than calcareous or tectinous, species. Foraminiferal density never exceeded that of metazoan meiofauna at any site. Foraminiferal biomass, however, exceeded metazoan meiofaunal biomass at five of the ten sites, indicating that foraminifera constitute a major component of the Gulf’s deep-water meiofaunal biomass.Funded by Minerals Management Service contract 1435-01-99-CT-30991 to G.T. Rowe (Texas A&M University)

A new method to analyse the pace of child development: Cox regression validated by a bootstrap resampling procedure

<p>Abstract</p> <p>Background</p> <p>Various perinatal factors influencing neuromotor development are known from cross sectional studies. Factors influencing the age at which distinct abilities are acquired are uncertain. We hypothesized that the Cox regression model might identify these factors.</p> <p>Methods</p> <p>Neonates treated at Aachen University Hospital in 2000/2001 were identified retrospectively (n = 796). Outcome data, based on a structured interview, were available from 466 children, as were perinatal data. Factors possibly related to outcome were identified by bootstrap selection and then included into a multivariate Cox regression model. To evaluate if the parental assessment might change with the time elapsed since birth we studied five age cohorts of 163 normally developed children.</p> <p>Results</p> <p>Birth weight, gestational age, congenital cardiac disease and periventricular leukomalacia were related to outcome in the multivariate analysis (p < 0.05). Analysis of the control cohorts revealed that the parents' assessment of the ability of bladder control is modified by the time elapsed since birth.</p> <p>Conclusions</p> <p>Combined application of the bootstrap resampling procedure and multivariate Cox regression analysis effectively identifies perinatal factors influencing the age at which distinct abilities are acquired. These were similar as known from previous cross sectional studies. Retrospective data acquistion may lead to a bias because the parental memories change with time. This recommends applying this statistical approach in larger prospective trials.</p

Pharmacotherapy and Pregnancy: Highlights from the Third International Conference for Individualized Pharmacotherapy in Pregnancy

To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration’s role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist’s role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the fetus when studying drugs in pregnancy. The Conference highlighted several areas of collaboration within the current Obstetrics Pharmacology Research Units Network and hoped to educate providers, researchers, and agencies with the common goal to improve the ability to safely and effectively use individualized pharmacotherapy in pregnancy

Automated psychological therapy using immersive virtual reality for treatment of fear of heights:a single-blind, parallel-group, randomised controlled trial

Background: Engaging, interactive, and automated virtual reality (VR) treatments might help solve the unmet needs of individuals with mental health disorders. We tested the efficacy of an automated cognitive intervention for fear of heights guided by an avatar virtual coach (animated using motion and voice capture of an actor) in VR and delivered with the latest consumer equipment. Methods: We did a randomised trial of automated VR versus usual care. We recruited adults aged older than 18 years with a fear of heights by radio advertisements in Oxfordshire, UK. We diagnosed fear of heights if participants scored more than 29 on the Heights Interpretation Questionnaire (HIQ). We randomly allocated participants by computer in a 1:1 ratio to either automated VR delivered in roughly six 30-min sessions administered about two to three times a week over a 2-week period (intervention group) or to usual care (control group). Randomisation was stratified by severity of fear of heights. The research team, who were unaware of the random allocation, administered three fear-of-height assessments, at baseline (0 weeks), at the end of treatment (2 weeks), and at follow-up (4 weeks). The primary outcome measure was HIQ score (range 16–80, with higher scores indicating greater severity). This trial is registered with the ISRCTN registry, number ISRCTN11898283. Findings: Between Nov 25, 2017, and Feb 27, 2018, 100 individuals were enrolled and underwent randomisation, of whom 49 were assigned to the VR treatment group and 51 to the control group. All participants completed the 4-week follow-up. The mean total treatment time in VR was 124·43 min (SD 34·23). Compared with participants in the control group, the VR treatment reduced fear of heights at the end of treatment (mean change score −24·5 [SD 13·1] in the VR group vs −1·2 [7·3] in the control group; adjusted difference −24·0, 95% CI −27·7 to −20·3; Cohen's d=2·0; p&lt;0·0001). The benefit was maintained at follow-up (mean change score −25·1 [SD 13·9] in the VR group vs −1·5 [7·8] in the control group; adjusted difference −24·3, 95% CI −27·9 to −20·6; Cohen's d=2·0; p&lt;0·0001). The number needed to treat to at least halve the fear of heights was 1·3. No adverse events were reported. Interpretation: Psychological therapy delivered automatically by a VR coach can produce large clinical benefits. Evidence-based VR treatments have the potential to greatly increase treatment provision for mental health disorders.</p