1. |
- Gamble, Carrol, et al.
(författare)
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Timing of Primary Surgery for Cleft Palate.
- 2023
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 389:9, s. 795-807
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Tidskriftsartikel (refereegranskat)abstract
- Among infants with isolated cleft palate, whether primary surgery at 6 months of age is more beneficial than surgery at 12 months of age with respect to speech outcomes, hearing outcomes, dentofacial development, and safety is unknown.We randomly assigned infants with nonsyndromic isolated cleft palate, in a 1:1 ratio, to undergo standardized primary surgery at 6 months of age (6-month group) or at 12 months of age (12-month group) for closure of the cleft. Standardized assessments of quality-checked video and audio recordings at 1, 3, and 5 years of age were performed independently by speech and language therapists who were unaware of the trial-group assignments. The primary outcome was velopharyngeal insufficiency at 5 years of age, defined as a velopharyngeal composite summary score of at least 4 (scores range from 0 to 6, with higher scores indicating greater severity). Secondary outcomes included speech development, postoperative complications, hearing sensitivity, dentofacial development, and growth.We randomly assigned 558 infants at 23 centers across Europe and South America to undergo surgery at 6 months of age (281 infants) or at 12 months of age (277 infants). Speech recordings from 235 infants (83.6%) in the 6-month group and 226 (81.6%) in the 12-month group were analyzable. Insufficient velopharyngeal function at 5 years of age was observed in 21 of 235 infants (8.9%) in the 6-month group as compared with 34 of 226 (15.0%) in the 12-month group (risk ratio, 0.59; 95% confidence interval, 0.36 to 0.99; P=0.04). Postoperative complications were infrequent and similar in the 6-month and 12-month groups. Four serious adverse events were reported (three in the 6-month group and one in the 12-month group) and had resolved at follow-up.Medically fit infants who underwent primary surgery for isolated cleft palate in adequately resourced settings at 6 months of age were less likely to have velopharyngeal insufficiency at the age of 5 years than those who had surgery at 12 months of age. (Funded by the National Institute of Dental and Craniofacial Research; TOPS ClinicalTrials.gov number, NCT00993551.).
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2. |
- Pirmohamed, Munir, et al.
(författare)
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A Randomized Trial of Genotype-Guided Dosing of Warfarin
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:24, s. 2294-2303
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Tidskriftsartikel (refereegranskat)abstract
- Background: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy.Methods: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639GA) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation.Results: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001).Conclusions: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy.
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3. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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4. |
- Almeida, Joao, et al.
(författare)
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Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 359-
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Tidskriftsartikel (refereegranskat)abstract
- Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes(2). Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases(2). However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere(3). It is thought that amines may enhance nucleation(4-16), but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
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5. |
- Conroy, Elizabeth J, et al.
(författare)
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A randomised controlled trial comparing palate surgery at 6months versus 12months of age (the TOPS trial): a statistical analysis plan.
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, hearing, dental development, and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. The Timing Of Primary Surgery for cleft palate (TOPS) trial aims to determine whether, in infants with cleft palate, it is better to perform primary surgery at age 6 or 12months (corrected for gestational age).The TOPS trial is an international, two-arm, parallel group, randomised controlled trial. The primary outcome is insufficient velopharyngeal function at 5years of age. Secondary outcomes, measured at 12months, 3years, and 5years of age, include measures ofspeech development, safety of the procedure, hearing level, middle ear function, dentofacial development, and growth. The analysis approaches for primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The TOPS protocol has been published previously.This paper provides details of the planned statistical analyses for the TOPS trial and will reduce the risk of outcome reporting bias and data-driven results.ClinicalTrials.gov NCT00993551 . Registered on 9 October 2009.
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6. |
- de Oliveira, Fabio Carlos Lucas, et al.
(författare)
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Association between the level of partial foot amputation and gait: a scoping review with implications for the minimum impairment criteria for wheelchair tennis
- 2022
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674.
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Tidskriftsartikel (refereegranskat)abstract
- Objective This scoping review examines how different levels and types of partial foot amputation affect gait and explores how these findings may affect the minimal impairment criteria for wheelchair tennis.Methods Four databases (PubMed, Embase, CINAHL and SPORTDiscus) were systematically searched in February 2021 for terms related to partial foot amputation and ambulation. The search was updated in February 2022. All study designs investigating gait-related outcomes in individuals with partial foot amputation were included and independently screened by two reviewers based on Arksey and O’Malley’s methodological framework and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews.Results Twenty-nine publications with data from 252 participants with partial foot amputation in 25 studies were analysed. Toe amputations were associated with minor gait abnormalities, and great toe amputations caused loss of push-off in a forward and lateral direction. Metatarsophalangeal amputations were associated with loss of stability and decreased gait speed. Ray amputations were associated with decreased gait speed and reduced lower extremity range of motion. Transmetatarsal amputations and more proximal amputations were associated with abnormal gait, substantial loss of power generation across the ankle and impaired mobility.Conclusions Partial foot amputation was associated with various gait changes, depending on the type of amputation. Different levels and types of foot amputation are likely to affect tennis performance. We recommend including first ray, transmetatarsal, Chopart and Lisfranc amputations in the minimum impairment criteria, excluding toe amputations (digits two to five), and we are unsure whether to include or exclude great toe, ray (two to five) and metatarsophalangeal amputations.Trial registration The protocol of this scoping review was previously registered at the Open Science Framework Registry (https://osf.io/8gh9y) and published.
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7. |
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8. |
- Kirkby, Jasper, et al.
(författare)
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Ion-induced nucleation of pure biogenic particles
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood(1). Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours(2). It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere(3,4), and that ions have a relatively minor role(5). Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded(6,7). Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of a-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.
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9. |
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10. |
- Lawler, Michael J., et al.
(författare)
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Unexpectedly acidic nanoparticles formed in dimethylamine-ammonia-sulfuric-acid nucleation experiments at CLOUD
- 2016
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:21, s. 13601-13618
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Tidskriftsartikel (refereegranskat)abstract
- New particle formation driven by acid-base chemistry was initiated in the CLOUD chamber at CERN by introducing atmospherically relevant levels of gas-phase sulfuric acid and dimethylamine (DMA). Ammonia was also present in the chamber as a gas-phase contaminant from earlier experiments. The composition of particles with volume median diameters (VMDs) as small as 10 nm was measured by the Thermal Desorption Chemical Ionization Mass Spectrometer (TDCIMS). Particulate ammonium-to-dimethylaminium ratios were higher than the gas-phase ammonia-to-DMA ratios, suggesting preferential uptake of ammonia over DMA for the collected 10-30 nm VMD particles. This behavior is not consistent with present nanoparticle physicochemical models, which predict a higher dimethylaminium fraction when NH3 and DMA are present at similar gas-phase concentrations. Despite the presence in the gas phase of at least 100 times higher base concentrations than sulfuric acid, the recently formed particles always had measured base : acid ratios lower than 1 : 1. The lowest base fractions were found in particles below 15 nm VMD, with a strong size-dependent composition gradient. The reasons for the very acidic composition remain uncertain, but a plausible explanation is that the particles did not reach thermodynamic equilibrium with respect to the bases due to rapid heterogeneous conversion of SO2 to sulfate. These results indicate that sulfuric acid does not require stabilization by ammonium or dimethylaminium as acid-base pairs in particles as small as 10 nm.
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11. |
- Lehtipalo, Katrianne, et al.
(författare)
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The effect of acid-base clustering and ions on the growth of atmospheric nano-particles
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.
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13. |
- Sanders, Ella, et al.
(författare)
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The stabilization of S100A9 structure by calcium inhibits the formation of amyloid fibrils
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:17
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Tidskriftsartikel (refereegranskat)abstract
- The calcium-binding protein S100A9 is recognized as an important component of the brain neuroinflammatory response to the onset and development of neurodegenerative disease. S100A9 is intrinsically amyloidogenic and in vivo co-aggregates with amyloid-β peptide and α-synuclein in Alzheimer’s and Parkinson’s diseases, respectively. It is widely accepted that calcium dyshomeostasis plays an important role in the onset and development of these diseases, and studies have shown that elevated levels of calcium limit the potential for S100A9 to adopt a fibrillar structure. The exact mechanism by which calcium exerts its influence on the aggregation process remains unclear. Here we demonstrate that despite S100A9 exhibiting α-helical secondary structure in the absence of calcium, the protein exhibits significant plasticity with interconversion between different conformational states occurring on the micro- to milli-second timescale. This plasticity allows the population of conformational states that favour the onset of fibril formation. Magic-angle spinning solid-state NMR studies of the resulting S100A9 fibrils reveal that the S100A9 adopts a single structurally well-defined rigid fibrillar core surrounded by a shell of approximately 15–20 mobile residues, a structure that persists even when fibrils are produced in the presence of calcium ions. These studies highlight how the dysregulation of metal ion concentrations can influence the conformational equilibria of this important neuroinflammatory protein to influence the rate and nature of the amyloid deposits formed.
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14. |
- Schomerus, Georg, et al.
(författare)
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Das Stigma von Suchterkrankungen verstehen und überwinden
- 2017
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Ingår i: SUCHT. - : Hogrefe Publishing Group. - 0939-5911 .- 1664-2856. ; 63:5, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- Stigmatisierung schadet den Betroffenen und verstärkt Suchtprobleme. Sie ist ein Hindernis auf dem Weg zur Hilfe, führt zu schlechterer Behandlung und vergrößert die sozialen und gesundheitlichen Folgen einer Suchtkrankheit. Das gilt sowohl für die individuellen Folgen als auch für die gesellschaftlichen einschließlich der öffentlichen Gesundheitskosten. Zudem ist Stigmatisierung ein ethisches Problem, weil sie eine bestimmte Gruppe benachteiligt und die Menschenwürde der Betroffenen angreift. Ein stigmafreier Umgang mit Suchtkrankheiten ist möglich. Entstigmatisierung bedeutet, bessere Lösungen für Suchtprobleme zu finden und verfügbar zu machen. Nicht Abwertung, Ausgrenzung und Disziplinierung, sondern Wertschätzung und Befähigung (Empowerment) müssen im Zentrum von Prävention, Behandlung sowie dem alltäglichen Umgang mit Suchtkrankheiten stehen.
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15. |
- Shaw, W, et al.
(författare)
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Timing Of Primary Surgery for cleft palate (TOPS): protocol for a randomised trial of palate surgery at 6 months versus 12 months of age
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, speech, hearing, dental development and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. This has led to palatal closure in one-stage procedures being carried out around the age of 12 months, but in some cases as early as 6 months. The primary objective of the Timing Of Primary Surgery for Cleft Palate (TOPS)trial is to determine whether surgery for cleft palate performed at 6 or 12 months of age is most beneficial for speech outcomes. Methods and analysis Infants with a diagnosis of non-syndromic isolated cleft palate will be randomised to receive standardised primary surgery (Sommerlad technique) for closure of the cleft at either 6 months or 12 months, corrected for gestational age. The primary outcome will be perceived insufficient velopharyngeal function at 5 years of age. Secondary outcomes measured across 12 months, 3 years and 5 years will include growth, safety of the procedure, dentofacial development, speech, hearing level and middle ear function. Video and audio recordings of speech will be collected in a standardised age-appropriate manner and analysed independently by multiple speech and language therapists. The trial aims to recruit and follow-up 300 participants per arm. Data will be analysed according to the intention-to-treat principle using a 5% significance level. All analyses will be prespecified within a full and detailed statistical analysis plan. Ethics and dissemination Ethical approval has been sought in each participating country according to country-specific procedures. Trial results will be presented at conferences, published in peer-reviewed journals and disseminated through relevant patient support groups.
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16. |
- Tröstl, Jasmin, et al.
(författare)
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The role of low-volatility organic compounds in initial particle growth in the atmosphere
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 527-531
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Tidskriftsartikel (refereegranskat)abstract
- About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday(1). Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres(2,3). In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles(4), thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth(5,6), leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer(7-10). Although recent studies(11-13) predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon(2), and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Kohler theory)(2,14), has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown(15) that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10(-4.5) micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10(-4.5) to 10(-0.5) micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.
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17. |
- Williamson, Morag, et al.
(författare)
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What is EFPTA for? : Some self-reflection at the 20 year milestone.
- 2024
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Ingår i: The age of psychology. - Helsinki, Finland. ; , s. 10-10
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Konferensbidrag (populärvet., debatt m.m.)abstract
- It’s 2024, and we have good cause to celebrate 20 years of EFPTA activity. We have grown and thrived as an organisation, and can list a number of achievements, including numerous successful eventsfor psychology teachers /educators both in-person and online, collaboration with other organisations involved in psychology /psychology education in Europe, research publications, and presentations at international conferences. We effectively adapted our activities during the pandemic, and we continue to attract new member countries and individuals. Presumably we – and others - see ourselves as doing something important; if so, what is that? Or do we just love to get together socially with like-minded folk? Bearing in mind the enormous changes in the environment over the last 20 years – from local/national education issues to global crises – what should be EFPTA’s purpose in the coming years? what challenges do we face? where should we focus our efforts? This participative discussion-based workshop will consider these and other related questions, with reference to our formal aims as well as participants’ experiences. It is hoped that these discussions will help inform EFPTA’s priorities in terms of future strategy.
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