Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort.

Background: Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. Method: The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Results: Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0 kg/m2, ß -0.037, 95% CI -0.058 to -0.016, P = .001), HADS depression score ≥8 (ß -0.159, -0.182 to -0.137, P < .001), anxiety score ≥8 (ß -0.090, -0.110 to -0.069, P < .001), taking ≥10 medications (ß -0.065, -0.085 to -0.046, P < .001), sarcopenia (ß -0.062, -0.080 to -0.043, P < .001) haemoglobin <100 g/L (ß -0.047, -0.085 to -0.010, P = .012) and pain (ß -0.134, -0.152 to -0.117, P < .001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Conclusion: Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.

Volatile lanthanide complexes with fluorinated heptadentate ligands.

Understanding factors that influence the volatility of lanthanide complexes remains an important goal for applications such as gas-phase f-metal separations and the synthesis of lanthanide-containing thin films. Lanthanide complexes often exhibit volatility differences that depend on the ability of ligands to saturate the lanthanide coordination sphere and attenuate intermolecular bonding in the solid state. This can make it difficult to assess how electronic factors associated with differing ligand substituents influence volatility. Here we describe the synthesis, structures, and thermal properties of a series of volatile lanthanide complexes (Ln = Nd, Er, and Yb) containing N4O3 ligands decorated with different alkyl and fluoroalkyl substituents (CF3, CF2CF2CF3, Me, and tBu). These ligands completely enveloped the tested lanthanides to form monomeric complexes with 7-coordinate distorted capped octahedral coordination geometries, as determined using single-crystal X-ray diffraction. Thermogravimetric analysis and bulk sublimation studies show how metal encapsulation affords complexes with the same volatility regardless of metal size, even with lanthanide ions with significantly different radii such as Nd3+ and Yb3+. Most notably, the results show that increasing ligand fluorination, a strategy often used to increase the volatility of metal complexes, is not always beneficial and can significantly attenuate the volatility of lanthanide complexes depending on location with respect to other substituents in the ligand framework. A pair-wise model based on density functional theory shows that the net intermolecular interactions in the unit cell can still be stronger when fluorination is present. In other words, even if individual interactions between neighboring molecules are weaker, the total number of interactions in the solid arising from the nature of crystal packing is equally important to consider.

Imaging actin organisation and dynamics in 3D.

The actin cytoskeleton plays a critical role in cell architecture and the control of fundamental processes including cell division, migration and survival. The dynamics and organisation of F-actin have been widely studied in a breadth of cell types on classical two-dimensional (2D) surfaces. Recent advances in optical microscopy have enabled interrogation of these cytoskeletal networks in cells within three-dimensional (3D) scaffolds, tissues and in vivo. Emerging studies indicate that the dimensionality experienced by cells has a profound impact on the structure and function of the cytoskeleton, with cells in 3D environments exhibiting cytoskeletal arrangements that differ to cells in 2D environments. However, the addition of a third (and fourth, with time) dimension leads to challenges in sample preparation, imaging and analysis, necessitating additional considerations to achieve the required signal-to-noise ratio and spatial and temporal resolution. Here, we summarise the current tools for imaging actin in a 3D context and highlight examples of the importance of this in understanding cytoskeletal biology and the challenges and opportunities in this domain.

Extracellular matrix stiffness activates mechanosensitive signals but limits breast cancer cell spheroid proliferation and invasion.

Breast cancer is characterized by physical changes that occur in the tumor microenvironment throughout growth and metastasis of tumors. Extracellular matrix stiffness increases as tumors develop and spread, with stiffer environments thought to correlate with poorer disease prognosis. Changes in extracellular stiffness and other physical characteristics are sensed by integrins which integrate these extracellular cues to intracellular signaling, resulting in modulation of proliferation and invasion. However, the co-ordination of mechano-sensitive signaling with functional changes to groups of tumor cells within 3-dimensional environments remains poorly understood. Here we provide evidence that increasing the stiffness of collagen scaffolds results in increased activation of ERK1/2 and YAP in human breast cancer cell spheroids. We also show that ERK1/2 acts upstream of YAP activation in this context. We further demonstrate that YAP, matrix metalloproteinases and actomyosin contractility are required for collagen remodeling, proliferation and invasion in lower stiffness scaffolds. However, the increased activation of these proteins in higher stiffness 3-dimensional collagen gels is correlated with reduced proliferation and reduced invasion of cancer cell spheroids. Our data collectively provide evidence that higher stiffness 3-dimensional environments induce mechano-signaling but contrary to evidence from 2-dimensional studies, this is not sufficient to promote pro-tumorigenic effects in breast cancer cell spheroids.

Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT.

Background: Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed. Objectives: To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption. Design: Multicentre, three-arm, parallel-group, randomised controlled clinical trial. Setting: Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands). Participants: Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate. Interventions: (1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation. Main outcome measures: Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule. Results: Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to -6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to -2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported. Limitations: The trial's primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted. Conclusions: Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate. Future work: Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence. Trial registration: This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.

Many people who are trying to stop drinking alcohol can find it difficult to remain alcohol free. There is a medication called acamprosate (Campral) that can reduce cravings thereby increasing the likelihood of abstinence. However, some people have trouble taking the right amount of acamprosate tablets needed every day at the right time, preferably at mealtimes. This means the medication is not as effective. We have tested some new ways to help support people taking acamprosate. We tested three different strategies to find the best way to support people taking acamprosate. We recruited 739 people aged 18 and over who were receiving alcohol treatment to stop drinking and were taking acamprosate. We randomly allocated these people to three groups. The first was Standard Support, the usual support people receive when taking acamprosate. The second group received Standard Support plus Medication Management. This consisted of 12 telephone calls over 6 months with a trained pharmacist to discuss the importance of taking the right amount of the medication, how the medication works and strategies to help people take the medication correctly. The third group received Standard Support, Medication Management and Contingency Management. This involved giving people shopping vouchers for participating with Medication Management calls. The maximum value of vouchers per person was £120. People who were in the group receiving Medication Management and Contingency Management took a greater number of acamprosate tablets. We also found that Medication Management plus Contingency Management was more cost-effective; there were greater gains in health with a smaller cost per person compared to Standard Support alone. This shows that there is likely to be a benefit to patients of Medication Management plus Contingency Management for supporting people taking acamprosate.

Agriculture and hot temperatures interactively erode the nest success of habitat generalist birds across the United States.

Habitat conversion and climate change are fundamental drivers of biodiversity loss worldwide but are often analyzed in isolation. We used a continental-scale, decades-long database of more than 150,000 bird nesting attempts to explore how extreme heat affects avian reproduction in forests, grasslands, and agricultural and developed areas across the US. We found that in forests, extreme heat increased nest success, but birds nesting in agricultural settings were much less likely to successfully fledge young when temperatures reached anomalously high levels. Species that build exposed cup nests and species of higher conservation concern were particularly vulnerable to maximum temperature anomalies in agricultural settings. Finally, future projections suggested that ongoing climate change may exacerbate the negative effects of habitat conversion on avian nesting success, thereby compromising conservation efforts in human-dominated landscapes.

Efficacy of Liquid Smoke to Mitigate Infestations of the Storage Mite, Tyrophagus putrescentiae, in a Model Semi-Moist Pet Food.

The storage mite Tyrophagus putrescentiae infests a wide range of food products including pet food. Control of this mite depends on chemical methods such as fumigation and spraying with insecticides. Methyl bromide was used as a fumigant for high-value stored products, especially to control mite infestation in dry-cured hams and cheeses, but it is now banned for most uses in many countries because of its atmospheric ozone-depleting effects. Effective alternatives to methyl bromide are needed to develop integrated pest management programs for this pest. Liquid smoke is a naturally derived flavoring and preservative with known antimicrobial properties. The objective of this study was to investigate the efficacy of liquid smoke preparations, with varying phenol and carbonyl concentrations and pH, on the survivability and orientation behavior of T. putrescentiae in a model semi-moist pet food. The mite survivability assays using liquid smoke-treated and untreated semi-moist pet food samples indicated that there was no difference among treatments (p > 0.05) for mite infestation and survival. Two-choice behavioral assays using semi-moist pet food cubes dipped in varying concentrations (0%, 0.3%, 1%, 5%, 10%, 25%, 50%, or 100% v/v) of liquid smoke preparations found that some of the liquid smoke preparations containing medium to high carbonyl content repelled the mites. In conclusion, liquid smoke did not kill or inhibit the mite population growth in semi-moist pet food. However, some liquid smoke fractions containing medium to high carbonyl content were repellent to mites and may retard mite infestation in stored semi-moist foods.

Quality standards for the management of alcohol-related liver disease: consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology ARLD special interest group.

OBJECTIVE: Alcohol-related liver disease (ALD) is the most common cause of liver-related ill health and liver-related deaths in the UK, and deaths from ALD have doubled in the last decade. The management of ALD requires treatment of both liver disease and alcohol use; this necessitates effective and constructive multidisciplinary working. To support this, we have developed quality standard recommendations for the management of ALD, based on evidence and consensus expert opinion, with the aim of improving patient care. DESIGN: A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology ALD Special Interest Group developed the quality standards, with input from the British Liver Trust and patient representatives. RESULTS: The standards cover three broad themes: the recognition and diagnosis of people with ALD in primary care and the liver outpatient clinic; the management of acutely decompensated ALD including acute alcohol-related hepatitis and the posthospital care of people with advanced liver disease due to ALD. Draft quality standards were initially developed by smaller working groups and then an anonymous modified Delphi voting process was conducted by the entire group to assess the level of agreement with each statement. Statements were included when agreement was 85% or greater. Twenty-four quality standards were produced from this process which support best practice. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice and an audit tool provided. CONCLUSION: It is hoped that services will review their practice against these recommendations and key performance indicators and institute service development where needed to improve the care of patients with ALD.

Factors associated with discharge against medical advice in alcohol withdrawal patients.

This study aimed to examine characteristics associated with discharge against medical advice from the hospital in alcohol withdrawal patients, supporting the work of hospital staff and Alcohol Care Teams and identifying characteristics that may help target patients most likely to discharge against medical advice. We used Hospital Episode Statistics Data to identify demographic and clinical variables and compare these in alcohol withdrawal patients who discharged against medical advice from hospital, compared with those who were discharged by the clinical team. Factors significantly associated with alcohol withdrawal patients discharging against medical advice from hospital were: being admitted as an emergency; discharged on a weekend; living with no fixed abode; being male; being younger and having a shorter length of stay. This study identifies characteristics that can be used to support acute hospitals and Alcohol Care Teams, particularly in the allocation of resources to reduce discharges against medical advice and subsequent readmissions to the hospital. Particular consideration should be given to clinical provision in hospitals in emergency departments and on weekends, and also those patients who are admitted and are of no fixed abode.

Efficacy of the Fumigants Propylene Oxide and Ethyl Formate to Control Two Pest Species of Dry-Cured Hams.

The ham mite Tyrophagus putrescentiae and the red-legged ham beetle Necrobia rufipes are harmful pests to several high-valued stored products. The regulatory phase-out of the fumigant methyl bromide necessitates the search for alternative fumigants. Propylene oxide (PPO) and ethyl formate (EF) were therefore evaluated in the laboratory for controlling these pests of dry-cured hams. Concentration-mortality studies at 25 °C of PPO and EF found that the mobile stages of the mites were very susceptible to low concentrations of 10 mg/L and less of each gas, while mite eggs were very tolerant and required 20 mg/L for PPO and 80 mg/L of EF for 100% mortality. Mixed life stage cultures of mites and beetles were treated for 24 h with either PPO or EF at 1× and 2× the estimated 99% lethal doses and confirmed effectiveness for controlling simulated pest populations. The sorptive properties of each gas in chambers with ham pieces, dog food kibbles, or fish meal were minimal for a reduction in mite toxicity when compared to treatments in empty chambers. There was no evidence that any desorbed gas occurred at a level toxic to mite eggs in any of the fumigated commodities. These fumigation studies with ham pests support further work with PPO and EF on any changes in the sensory quality of dry-cured hams for human taste and for commercial-scale fumigations toward regulatory approval.

Occurrence of adverse events and change in disease activity after initiation of etanercept in paediatric patients with juvenile psoriatic arthritis in the CARRA Registry.

OBJECTIVE: Etanercept is commonly used to treat juvenile idiopathic arthritis, including juvenile psoriatic arthritis (JPsA); however, information on etanercept's safety and effectiveness in clinical practice is limited. We used data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry to evaluate etanercept's safety and effectiveness in JPsA in clinical practice. METHODS: We analysed safety and effectiveness data for paediatric patients enrolled in the CARRA Registry who had a JPsA diagnosis and had used etanercept. Safety was assessed by calculating rates of prespecified adverse events of special interest (AESIs) and serious adverse events (SAEs). Effectiveness was assessed by a variety of disease activity measures. RESULTS: Overall, 226 patients had JPsA and received etanercept; 191 met criteria for safety analysis and 43 met criteria for effectiveness analysis. AESI and SAE incidence rates were low. There were five events: three uveitis, one new-onset neuropathy and one malignancy. Incidence rates were 0.55 (95% CI: 0.18, 1.69), 0.18 (95% CI: 0.03, 1.29) and 0.13 (95% CI: 0.02, 0.09) per 100 patient-years for uveitis, neuropathy and malignancy, respectively. Etanercept showed effectiveness for JPsA treatment; 7 of 15 (46.7%) had an American College of Rheumatology-Pediatric Response 90, 9 of 25 (36.0%) had a clinical Juvenile Arthritis Disease Activity Score 10-joint ≤1.1 and 14 of 27 (51.9%) had clinically inactive disease at the 6-month follow-up. CONCLUSION: Data in the CARRA Registry showed that etanercept treatment was safe in treating children with JPsA, with low AESIs and SAEs. Etanercept was also effective, even when assessed in a small sample size.

Using liquid smoke to control infestations of the ham mite, Tyrophagus putrescentiae, on dry-cured hams during aging.

Eight treatments of edible coatings and nets including liquid smoke (SP and 24P) and xanthan gum (XG) were used to evaluate their effectiveness at controlling mite growth on dry-cured hams. Mite growth was controlled (P < 0.05) in both coating and netting treatments of 1% SP + 1% XG. Increasing SP concentration from 1% to 2% in the SP only treatments without XG did not control mite growth (P > 0.05) in the coating but controlled mite growth (P < 0.05) when infused in the nets. Both coating and netting treatments with 2% 24P + 1% XG controlled mite growth (P < 0.05), and ham cubes with 1% and 2% 24P in infused nets had mite numbers of 4.6 and 9.4, respectively. SP did not impact the sensory attributes of the ham. Results indicate that liquid smoke can potentially be added in coatings or ham nets to control mites and used in an integrated pest management program for dry-cured hams.

A method for reproducible high-resolution imaging of 3D cancer cell spheroids.

Multicellular tumour cell spheroids embedded within three-dimensional (3D) hydrogels or extracellular matrices (ECM) are widely used as models to study cancer growth and invasion. Standard methods to embed spheroids in 3D matrices result in random placement in space which limits the use of inverted fluorescence microscopy techniques, and thus the resolution that can be achieved to image molecular detail within the intact spheroid. Here, we leverage UV photolithography to microfabricate PDMS (polydimethylsiloxane) stamps that allow for generation of high-content, reproducible well-like structures in multiple different imaging chambers. Addition of multicellular tumour spheroids into stamped collagen structures allows for precise positioning of spheroids in 3D space for reproducible high-/super-resolution imaging. Embedded spheroids can be imaged live or fixed and are amenable to immunostaining, allowing for greater flexibility of experimental approaches. We describe the use of these spheroid imaging chambers to analyse cell invasion, cell-ECM interaction, ECM alignment, force-dependent intracellular protein dynamics and extension of fine actin-based protrusions with a variety of commonly used inverted microscope platforms. This method enables reproducible, high-/super-resolution live imaging of multiple tumour spheroids, that can be potentially extended to visualise organoids and other more complex 3D in vitro systems.

The Effect of Residual Pesticide Application on Microbiomes of the Storage Mite Tyrophagus putrescentiae.

Arthropods can host well-developed microbial communities, and such microbes can degrade pesticides and confer tolerance to most types of pests. Two cultures of the stored-product mite Tyrophagus putrescentiae, one with a symbiotic microbiome containing Wolbachia and the other without Wolbachia, were compared on pesticide residue (organophosphate: pirimiphos-methyl and pyrethroid: deltamethrin, deltamethrin + piperonyl butoxide)-containing diets. The microbiomes from mite bodies, mite feces and debris from the spent mite diet were analyzed using barcode sequencing. Pesticide tolerance was different among mite cultures and organophosphate and pyrethroid pesticides. The pesticide residues influenced the microbiome composition in both cultures but without any remarkable trend for mite cultures with and without Wolbachia. The most influenced bacterial taxa were Bartonella-like and Bacillus for both cultures and Wolbachia for the culture containing this symbiont. However, there was no direct evidence of any effect of Wolbachia on pesticide tolerance. The high pesticide concentration residues in diets reduced Wolbachia, Bartonella-like and Bacillus in mites of the symbiotic culture. This effect was low for Bartonella-like and Bacillus in the asymbiotic microbiome culture. The results showed that the microbiomes of mites are affected by pesticide residues in the diets, but the effect is not systemic. No actual detoxification effect by the microbiome was observed for the tested pesticides.

Dosing Variation at Initiation of Adalimumab and Etanercept and Clinical Outcomes in Juvenile Idiopathic Arthritis: A Childhood Arthritis and Rheumatology Research Alliance Registry Study.

OBJECTIVE: To determine the dose-response relationship of tumor necrosis factor (TNF) inhibition in the treatment of juvenile idiopathic arthritis (JIA). METHODS: Participants of the Childhood Arthritis and Rheumatology Research Alliance Registry were eligible for inclusion in the analyses if they started TNF inhibition treatment for JIA. The primary treatment response was determined 3 to 7 months after the start of treatment, based on the JIA American College of Rheumatology Pediatric criteria for improvement, clinical Juvenile Arthritis Disease Activity Score, and persistence of treatment after 6 months. Subsequently, pooled logistic regression models were performed to include long-term follow-up data. The models were adjusted for risk factors associated with poor treatment response. Dosing was expressed by body weight, body surface area, ideal body weight, fat free mass, and lean body mass. RESULTS: Participants treated with adalimumab (n = 328) and etanercept (n = 437) were included in the analyses (median dose 0.82 mg/kg body weight [interquartile range (IQR) 0.66-1.04] and 0.83 mg/kg body weight [IQR 0.75-0.95], respectively). The majority of analyses did not show a relationship between dose and outcome. Where associations were found, results were conflicting. Alternative dosing characteristics based on ideal body weight, fat free mass, and lean body mass did not result in stronger or more consistent associations. CONCLUSION: This study was not able to confirm our hypothesis that increased dosing of TNF inhibitors results in improved treatment outcomes. Although adjustment was performed for risk factors of impaired treatment response, residual confounding by indication likely explains the negative associations found in this study.

Trajectories of disease activity in patients with JIA in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. METHODS: JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. RESULTS: Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n = 199, 26.7%); High, Slowly Decreasing (HSD) (n = 154, 20.6%); High, Increasing (HI) (n = 39, 5.2%); Moderate, Persistent (MP) (n = 218, 29.2%); and Moderate, Decreasing (MD) (n = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. CONCLUSIONS: Five trajectories of JIA disease activity, and associated baseline variables, were identified.

Disease Recapture Rates After Medication Discontinuation and Flare in Juvenile Idiopathic Arthritis: An Observational Study Within the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: Children with well-controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare. METHODS: Children with JIA who discontinued conventional synthetic or biologic disease-modifying antirheumatic drugs for well-controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare. RESULTS: A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P = 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22-18.78] and OR 2.74 [95% CI 1.62-4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72-0.95]). CONCLUSION: Approximately half of JIA flares post-discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision-making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed.

Polymeric Materials and Microfabrication Techniques for Liquid Filtration Membranes.

This review surveys and summarizes the materials and methods used to make liquid filtration membranes. Examples of each method including phase inversion, electrospinning, interfacial polymerization, thin film composites, stretching, lithography and templating techniques, are given and the pros and cons of each method are discussed. Trends of recent literature are also discussed and their potential direction is deliberated. Furthermore, the polymeric materials used in the fabrication process of liquid filtration membranes are also reviewed and trends and similarities are shown and discussed. Thin film composites and selective filtration applications appear to be a growing area of research for membrane technology. Other than the required mechanical properties (tensile strength, toughness and chemical and thermal stability), it becomes apparent that polymer solubility and hydropathy are key factors in determining their applicability for use as a membrane material.

Pesticide residue exposure provides different responses of the microbiomes of distinct cultures of the stored product pest mite Acarus siro.

BACKGROUND: The contribution of the microbiome to pesticide breakdown in agricultural pests remains unclear. We analyzed the effect of pirimiphos-methyl (PM) on four geographically different cultures of the stored product pest mite Acarus siro (6 L, 6Tu, 6Tk and 6Z) under laboratory experiments. The effect of PM on mite mortality in the impregnated filter paper test was compared. RESULTS: The mite sensitivity to PM decreased in the order of 6 L, 6Tu, 6Tk, and 6Z. Then, the mites were cultured on PM residues (0.0125 and 1.25 µg·g-1), and population growth was compared to the control after 21 days of exposure. The comparison showed two situations: (i) increasing population growth for the most sensitive cultures (6 L and 6Tu), and (ii) no effect on mite population growth for tolerant cultures (6Z and 6Tk). The microbiome of mites was analyzed by quantification of 16S DNA copies based on quantitative polymerase chain reaction (qPCR) and by barcode sequencing of the V4 fragment of 16S DNA on samples of 30 individuals from the control and PM residues. The microbiome comprised primarily Solitalea-like organisms in all cultures, except for 6Z, followed by Bacillus, Staphylococcus, and Lactobacillus. The microbiomes of mite cultures did not change with increasing population density. The microbiome of cultures without any differences in population density showed differences in the microbiome composition. A Sodalis-like symbiont replaced Solitalea in the 1.25 µg·g-1 PM in the 6Tk culture. Sodalis and Bacillus prevailed in the microbiomes of PM-treated mites of 6Z culture, while Solitalea was almost absent. CONCLUSION: The results showed that the microbiome of A. siro differs in composition and in response to PM residues in the diet. The results indicate that Sodalis-like symbionts can help recover mites from pesticide-induced stress.