Cascades of Parametric Instabilities in the Tokamak Plasma Edge during Electron Cyclotron Resonance Heating.

We report observations of nonlinear two-plasmon decay instabilities (TPDIs) of a high-power microwave beam, a process similar to half-harmonic generation in optics, during electron cyclotron resonance heating in a tokamak. TPDIs are found to occur regularly in the plasma edge due to wave trapping in density fluctuations for various confinement modes, and the frequencies of both observed daughter waves agree with modeling. Emissions from a cascade of subsequent decays, which indicate a generation of ion Bernstein waves, are correlated with fast-ion generation. This emphasizes the limitations of standard linear microwave propagation models and possibly paves the way for novel microwave applications in plasmas.

Prognostic genomic alterations in patients undergoing liver resection for hepatocellular carcinoma.

INTRODUCTION: Genetic mutations and amplifications found in hepatocellular carcinoma (HCC) have a potentially prognostic impact. The aim of this study was to investigate the prognostic value of mutations and amplifications in HCC from patients that were liver resected. METHODS: Patients liver resected for HCC at Copenhagen University Hospital Rigshospitalet between May 2014 and January 2018 were included. DNA from freshly frozen tumour tissue was investigated with TruSight Oncology 500. Mutations and amplifications were correlated with disease-free survival and overall survival using multivariate Cox regression to assess the effect on prognosis. RESULTS: Of the 51 patients included, 88% were male and the median age was 69 years. Most patients had a single tumour (84%) with no vascular invasion (67%) in a non-cirrhotic liver (76% with fibrosis, 24% with cirrhosis). The median follow-up was 37 months. Patients with a MYC amplification (8%) were significantly younger than the remaining patients. Furthermore, they had a significantly shorter overall survival (15 months (95% CI: 0.0-31.6) vs. 59 months (95% CI: 34.4-83.6), p = < 0.001) and disease-free survival (8 months (95% CI: 4.6-11.4) vs. 19 months (95% CI: 12.3-25.7), p = 0.03). However, only overall survival remained statistically significant in the adjusted analysis. Furthermore, all patients with an ARID1A mutation (6%) had microvascular invasion and significantly larger tumours than the patients without ARID1A mutation. CONCLUSION: MYC amplifications had a prognostic influence on survival, whereas ARID1A gene mutations were correlated with microvascular invasion. These may serve as prognostic biomarkers and should be validated in large, independent cohort.

Tinkering with care: Implementing extended-release buprenorphine depot treatment for opioid dependence.

We examine how extended-release buprenorphine depot (BUP-XR) is put to use and made to work in implementation practices, attending to how care practices are challenged and adapted as a long-acting technology is introduced into service in opioid agonist treatment (OAT) in Australia. Our approach is informed by ideas in science and technology studies (STS) emphasising the irreducible entanglement of care practices and technology, and in particular the concept of 'tinkering' as a practice of adaptation. To make our analysis, we draw on qualitative interview accounts (n = 19) of service providers involved in BUP-XR implementation across five sites. Our analysis considers the disruptive novelty of BUP-XR. Tinkering to make a novel technology work in practice slows down the expectation of implementation in relation to transformative innovation, despite the promise of dramatic or rapid change. Tinkering allowed for more open relations, for new care practices that departed from the routine and familiar, opening potential for how BUP-XR could be put to use and made to work in its new situation, and as its situation evolved along-with its implementation. Flexibility and openness of altering relations was, however, at times, held in tension with inflexibility and closure. This analysis identifies a concern for what is made present and what is made absent in the altered care network affected by BUP-XR, with the multiple effects of supervised daily dosing practices thrown into relief as they become absented. Tinkering to implement BUP-XR locally connects with a broader assemblage of trial and movement in the constitution of treatment. The introduction of long-acting technologies prompts new questions about embedded implementation practices, including supervised dosing, urinalysis, the time and place of psychosocial support, and how other social aspects of care might be recalibrated in drug treatment.

Development of the 174 GHz collective Thomson scattering diagnostics at Wendelstein 7-X.

In this paper, we present the design and commissioning results of the upgraded collective Thomson scattering diagnostic at the Wendelstein 7-X stellarator. The diagnostic has a new radiometer designed to operate between the second and third harmonics of the electron cyclotron emission from the plasma at 171-177 GHz, where the emission background has a minimum and is of order 10-100 eV. It allows us to receive the scattered electromagnetic field with a significantly improved signal-to-noise ratio and extends the set of possible scattering geometries compared to the case of the original instrument operated at 140 GHz. The elements of the diagnostic are a narrowband notch filter and a frequency stabilized probing gyrotron that will allow measuring scattered radiation spectra very close to the probing frequency. Here, we characterize the microwave components applied to the radiometer and demonstrate the performance of the complete system that was achieved during the latest experimental campaign, OP2.1.

Accuracy of three diagnostic tests to detect tooth resorption in unowned unsocialised cats in Denmark.

OBJECTIVES: To estimate the relative diagnostic sensitivity and specificity of oral clinical examination, full-mouth dental radiography, and cone-beam CT for the detection of tooth resorption in cats, and to estimate the prevalence of tooth resorption in unowned, unsocialised cats in Denmark. MATERIALS AND METHODS: Cadavers of 144 adult cats underwent an oral examination, full-mouth dental radiography, and cone-beam CT. Sensitivity and specificity of the three tests, along with the true prevalence, overall and stratified by sex and tooth location, were estimated using latent class methods. RESULTS: We found cone-beam CT to be the superior image modality, with a sensitivity of 99.5% and a specificity of 99.8%. Dental radiography had a sensitivity of 78.9% and a specificity of 100%, and oral clinical examination had a sensitivity of only 36.0% and specificity of 99.9%. We estimated the prevalence of tooth resorption among unowned unsocialised cats in Denmark to be 40% of adult individuals, and 6.1% of teeth. CLINICAL SIGNIFICANCE: When dealing with tooth resorption, cone-beam CT can help the operator to find and treat affected teeth that could otherwise go undiagnosed. The prevalence of tooth resorption among unowned, unsocialised cats in Denmark does not appear to differ from other populations of cats.

Treatment-related changes in serum neutrophil gelatinase-associated lipocalin (NGAL) in psoriatic arthritis: results from the PIPA cohort study.

OBJECTIVES: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment. METHOD: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay. RESULTS: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes. CONCLUSION: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Variability in indigenous Pakistani tomato lines and worldwide reference collection for Tomato Mosaic Virus (ToMV) and Tomato Yellow Leaf Curl Virus (TYLCV) infection

Abstract Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.

RESUMO O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.

Variability in indigenous Pakistani tomato lines and worldwide reference collection for Tomato Mosaic Virus (ToMV) and Tomato Yellow Leaf Curl Virus (TYLCV) infection / Variabilidade em linhagens indígenas de tomate do Paquistão e coleção de referência global para infecção por vírus do mosaico do tomateiro (ToMV) e vírus da folha amarela do tomate (TYLCV)

Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.

O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.

Co-designing a Canadian adaptation of a lifestyle-oriented intervention aimed to improve daily functioning of individuals living with chronic pain: a multi-method study protocol of REVEAL(OT) Canada.

Background: Living with chronic pain (CP) often implies major lifestyle changes, including modifications of daily routines and work. Surprisingly, few validated and effective interventions specifically target functional outcomes in this population. Redesign your Everyday Activities and Lifestyle with Occupational Therapy [REVEAL(OT)] is a lifestyle-oriented intervention led by occupational therapists that directly targets the daily functional challenges of living with CP. The intervention was initially developed and studied as an add-on to standard treatment delivered by Danish multidisciplinary specialized pain clinics. Adapting, implementing, and evaluating REVEAL(OT) within the Canadian healthcare system will contribute to broadening the scope of treatments offered in specialized pain clinics that do not yet include occupational therapy. Objective: The proposed study aims to define and refine REVEAL(OT)/CA with partners (authors of original intervention, people with lived experience, clinicians, managers). Methods: This participatory action research will use a multi-method design and follow the ORBIT model for developing behavioral treatments for chronic diseases. A process of co-construction with partners and an advisory committee will take place in two Montreal specialized pain clinics. It consists of two related work packages (WPs). In WP1, a first series of focus groups with partners (n = 86) and workshops with the advisory committee will be conducted to co-develop the hypothetical pathway describing intervention components and their potential mechanisms of action on targeted outcomes, as well as the first version of the adapted intervention manual. WP2 will co-refine REVEAL(OT)/CA by exploring its acceptability, feasibility and mechanisms of action through intervention deliveries (at least twice in each of two specialized pain clinics; n ≥ 60 patients) and focus groups and/or individual interviews with participating patients and partners. At the end of this study, the intervention manual will be generated both in French and English. Discussion: This study will set the stage for subsequent implementation and effectiveness assessment projects and be an important step towards the deployment of interventions aiming to improve engagement in meaningful daily activities among adults living with CP. Registration: OSF Registries, osf.io/8gksa. Registered 3 August 2023, https://osf.io/8gksa.

Dairy cattle welfare - the relative effect of legislation, industry standards and labelled niche production in five European countries.

The only common European Union (EU) legislation set up specifically to ensure the welfare of dairy cattle is for calves. As a consequence, there is wide diversity in how dairy cattle welfare is ensured in EU countries. A few countries have legal requirements for dairy cattle welfare, while in others, it is left to industry standards or niche production requirements, typically linked to various premium labels. In this paper, we compared animal welfare provisions in dairy cattle production across five countries with different combinations of legislative and other approaches: Denmark, Germany, the Netherlands, Sweden, and the United Kingdom. Firstly, we aimed to map the diversity of animal welfare initiatives. Secondly, we used the Benchmark method of expert valuations and weightings of the relative importance of individual welfare provisions. We found that Denmark and Sweden have the highest level of dairy cattle welfare provisions as measured by the Benchmark method, partly due to high legislative welfare requirements, followed by the United Kingdom, which has an extensive industry standard with very high uptake. Germany and the Netherlands, on the other hand, have lower levels of documented welfare provisions, and correspondingly a Benchmark score closer to a baseline defined by legal requirements at EU level. We also found differences in what elements of animal welfare were focussed on. Some initiatives emphasised fulfilling the social needs of cattle, while others focused more on space and freedom to move. Also, the countries with the highest Benchmark score had a relatively high level of production of organic and other specialty dairy products. We found the effect of national legislation or ambitious industry standards on dairy cattle welfare to be much larger than previous studies have found in either pigs or poultry. At a time when the EU is considering stepping up its efforts to improve animal welfare in terms of common minimum standards, the results of this study could have important policy implications. The diversity in the level of dairy cattle welfare standards found across countries may speak in favour of having shared minimum standards, both at EU level and globally. However, even among countries with a similar Benchmark score, we found a difference in the kinds of welfare provisions at work, which may make full harmonisation of standards more challenging.

Novel details on the dissociation of casein micelle suspensions as a function of pH and temperature.

Membrane filtration is a widespread process for fractionation and recombination of milk components. Although the dissociation of micellar caseins has been studied in detail in skim milk, it is important to better understand the dissociation dynamics occurring between the colloidal and noncolloidal fractions in systems of modified composition. This research aimed at understanding the dissociation of casein proteins in micellar fractions depleted of whey proteins. Casein micelle dispersions were tested at neutral pH and pH 6 (using glucono-δ-lactone as acidulant), after incubation at 4°C or 22°C, and compared with skim milk. The ionic composition of the serum phase was measured using inductively coupled plasma-mass spectrometry, and the protein distribution analyzed using reversed phase-HPLC coupled with mass spectrometry. When incubated at 22°C, there were no differences in casein micelle dissociation between skim milk and whey protein-depleted micelles (∼2.6% dissociated casein). No additional dissociation occurred by lowering the pH from 6.8 to 6 at 22°C, albeit there were more soluble ions at low pH (71% Ca and 65% P). At 4°C, there was an increased amount of ß-casein found in the serum phase (23-33% of total ß-casein). In addition, there was an uneven dissociation behavior of the various genetic ß-casein variants, whereof A2 was more readily released with cooling. In skim milk, approximately 22%, 18%, and 14% of κ-, αS2, and αS1-caseins, respectively, were dissociated from the micellar phase upon cooling and acidification to pH 6.0. This was in contrast to whey protein-depleted casein suspensions, in which only 6%, 5%, and 3% of κ-, αS2, and αS1-caseins, respectively, had dissociated. The results suggested that the whey proteins in the serum phase play a role in the equilibrium between colloidal and soluble caseins in milk. This is of great relevance in processes such as cold membrane fractionation, where more attention should be given to the protein composition in the serum phase, especially when concentration is combined with fractionation of the serum proteins.

The impact of COVID-19 public health measures on attendance and overdose at supervised injecting facilities in Australia.

OBJECTIVES: The COVID-19 pandemic disrupted service provision of harm reduction and drug treatment services for people who inject drugs in many countries. The two supervised injecting facilities (SIFs) in Sydney and Melbourne were differentially impacted by the pandemic, requiring local procedural changes in each service. We aimed to examine the impact of pandemic responses (including restrictions on movement, known as 'lockdowns') on service use and key parameters such as client reports of drug injected and recorded overdose rates. STUDY DESIGN: Time series analysis of weekly client visits and monthly overdoses occurring at each service. METHODS: Administrative client data from the two SIFs (Sydney data from 1 January 2018 to 30 April 2022; Melbourne data from 1 July 2018 to 30 April 2022) were examined using interrupted time series analyses with lockdown dates in each state entered as interruption terms. We analysed weekly SIF visits overall and by drug type, and monthly rates of opioid overdose at each service. RESULTS: Lockdowns resulted in decreased visits to both services. The number of weekly client visits decreased during the first national lockdown for both the Sydney (trend change = -57.9; 95% CI [-109.4, -6.4]) and Melbourne SIF (near sig trend change = -54.8 [-110.8, 1.05]). Trends in visit numbers increased after lockdowns were lifted in each city; however, visits in Sydney have not returned to the numbers recorded prior to the pandemic. Visits to the Melbourne SIF related to heroin use declined at each lockdown (trend 1 = -42.7 [-81.5, -3.9]; trend 2 = -56.1 [-94.6, -17.7]; trend 3 = -33.8 [-67.4, -0.2]); heroin visits to the Sydney SIF declined during the first lockdown and remained low (trend = -55.6 [-82.8, -28.3]). Methamphetamine visits to the Sydney SIF fluctuated, surpassing heroin visits at several timepoints. Rates of monthly opioid overdoses at both services declined immediately following the start of the first lockdown (Sydney = -16.6 [-26.1, -6.8]; Melbourne = -6.4 [-8.7, -4.1]), with increasing trends recorded at the end of the final lockdown in each jurisdiction (Sydney = 2.8 [0.6, 5.0]; Melbourne = 1.3 [0.72, 3.2]). CONCLUSIONS: Public health restrictions related to the COVID-19 pandemic were associated with reduced client visits to, and overdoses in, Australian SIFs. Variations were noted in the drugs injected, likely reflecting changes in local drug markets. Shifts to other drugs during these periods were evident: methamphetamine in Sydney; co-injection of heroin and diphenhydramine in Melbourne.

Trace elements in the culturally significant plant Sarracenia purpurea in proximity to dust sources in the oil sands region of Alberta, Canada.

Accessible populations of plants are critical to the meaningful exercise of Aboriginal and treaty rights in Canada. In the oil sands region of Alberta, populations of culturally significant plant species overlap with extensive oil and gas development. This has led to a host of questions and concerns related to plant health and integrity from both Indigenous communities and western scientists. Here, we assessed trace element concentrations in the northern pitcher-plant (tsala' t'ile; Sarracenia purpurea L.) with a focus on elements associated with fugitive dust and bitumen. Plant leaves were collected using clean methods and washed prior to analyses in an ultra-clean, metal-free laboratory. Pitcher-plant was an excellent model for assessing the impacts of industrial development on a culturally important, vulnerable species. Although concentrations of trace elements in pitcher-plant were low and not indicative of a toxicological concern, we saw clear dust signatures in plant tissues related to road and surface mine proximity. Elements associated with fugitive dust and bitumen extraction declined exponentially with increasing distance from a surface mine, a well-established regional pattern. However, our analyses also captured localized spikes in trace element concentrations within 300 m of unpaved roads. These local patterns are more poorly quantified at the regional scale but are indicative of the burden to Indigenous harvesters wishing to access plant populations that are not impacted by dust. Further work to directly quantify dust loads on culturally significant plants will help to define the amount of harvesting area lost to Indigenous communities due to dust impacts.

Federated vs Local vs Central Deep Learning of Tooth Segmentation on Panoramic Radiographs.

OBJECTIVE: Federated Learning (FL) enables collaborative training of artificial intelligence (AI) models from multiple data sources without directly sharing data. Due to the large amount of sensitive data in dentistry, FL may be particularly relevant for oral and dental research and applications. This study, for the first time, employed FL for a dental task, automated tooth segmentation on panoramic radiographs. METHODS: We employed a dataset of 4,177 panoramic radiographs collected from nine different centers (n = 143 to n = 1881 per center) across the globe and used FL to train a machine learning model for tooth segmentation. FL performance was compared against Local Learning (LL), i.e., training models on isolated data from each center (assuming data sharing not to be an option). Further, the performance gap to Central Learning (CL), i.e., training on centrally pooled data (based on data sharing agreements) was quantified. Generalizability of models was evaluated on a pooled test dataset from all centers. RESULTS: For 8 out of 9 centers, FL outperformed LL with statistical significance (p<0.05); only the center providing the largest amount of data FL did not have such an advantage. For generalizability, FL outperformed LL across all centers. CL surpassed both FL and LL for performance and generalizability. CONCLUSION: If data pooling (for CL) is not feasible, FL is shown to be a useful alternative to train performant and, more importantly, generalizable deep learning models in dentistry, where data protection barriers are high. CLINICAL SIGNIFICANCE: This study proves the validity and utility of FL in the field of dentistry, which encourages researchers to adopt this method to improve the generalizability of dental AI models and ease their transition to the clinical environment.

Effectiveness of patient education as a stand-alone intervention for patients with chronic widespread pain and fibromyalgia: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: Patient education is recommended as an integral component of the therapeutic plan for the management of chronic widespread pain (CWP) and fibromyalgia (FM). The key purpose of patient education is to increase the patient's competence to manage his or her own health requirements, encouraging self-management and a return to desired everyday activities and lifestyle. The aim of this systematic review was to evaluate the evidence for the benefits and potential harms associated with the use of patient education as a stand-alone intervention for individuals with CWP and FM through randomized controlled trials (RCTs). METHOD: On 24 November 2021 a systematic search of PubMed, MEDLINE, Embase, CENTRAL, PsycINFO, CINAHL, ClinicalTrials.gov, American College of Rheumatology, European League Against Rheumatism, and the World Health Organization International Clinical Trials Registry Platform identified 2069 studies. After full-text screening, five RCT studies were found to be eligible for the qualitative evidence synthesis. RESULTS: Patient education as a stand-alone intervention presented an improvement in patients' global assessment (standardized mean difference 0.79, 95% confidence interval 0.13 to 1.46). When comparing patient education with usual care, no intervention, or waiting list, no differences were found for functioning, level of pain, emotional distress in regard to anxiety and depression, or pain cognition. CONCLUSION: This review reveals the need for RCTs investigating patient education as a stand-alone intervention for patients with FM, measuring outcomes such as disease acceptance, health-related quality of life, enhancement of patients' knowledge of pain, pain coping skills, and evaluation of prioritized learning outcomes.

Degassing of early-formed planetesimals restricted water delivery to Earth.

The timing of delivery and the types of body that contributed volatiles to the terrestrial planets remain highly debated1,2. For example, it is unknown if differentiated bodies, such as that responsible for the Moon-forming giant impact, could have delivered substantial volatiles3,4 or if smaller, undifferentiated objects were more probable vehicles of water delivery5-7. Here we show that the water contents of minerals in achondrite meteorites (mantles or crusts of differentiated planetesimals) from both the inner and outer portions of the early Solar System are ≤2 µg g-1 H2O. These are among the lowest values ever reported for extraterrestrial minerals. Our results demonstrate that differentiated planetesimals efficiently degassed before or during melting. This finding implies that substantial amounts of water could only have been delivered to Earth by means of unmelted material.

Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial.

OBJECTIVE: To identify contextual factors that modify the treatment effect of the 'Good Life with osteoArthritis in Denmark' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). METHODS: Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. RESULTS: Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). CONCLUSIONS: These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71.