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Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis
In a randomized trial, children with uveitis associated with juvenile idiopathic arthritis who were taking a stable dose of methotrexate were significantly less likely to have treatment failure but more likely to have adverse events with adalimumab than with placebo.
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Children with JIA are at risk for inflammation of the uvea (uveitis). Uveitis develops in approximately 12 to 38% of patients with JIA within 7 years after the onset of arthritis.
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Despite current screening and therapeutic options, visual impairment in both eyes may develop in up to 15% of children with JIA-associated uveitis, and they may be certified as legally blind.
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Experimental models of autoimmune uveitis have shown that tumor necrosis factor α (TNF-α) plays a pivotal role in the pathogenesis,
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findings that have been borne . . .
Journal Article
Poemhood, our black revival : history, folklore & the Black experience: a young adult poetry anthology
Featuring contributions from an award-winning, bestselling group of Black voices, past and present, this powerful poetry anthology elicits vital conversations about race, belonging, history and faith to highlight Black joy and pain.
Book
You Understand, So I Understand: How a “Community of Knowledge” Shapes Trust and Credibility in Expert Testimony Evidence
Sloman and Rabb found support for the existence of the community of knowledge (CK) effect, which occurs when individuals are more likely to report understanding and being able to explain even fake scientific information when told that an expert understands the information. To date, no studies have been conducted that attempted to replicate original findings, let alone test the presence of the CK effect in realistic, legal scenarios. Therefore, Study One replicated original CK effect studies in a jury-eligible M-Turk sample (N = 291) using both Sloman and Rabb’s experimental stimuli as well as new stimuli. Study Two then tested the presence of the CK effect using scientific testimony in a mock court hearing from a forensic evaluator (N = 396). Not only did the CK effect improve laypeople’s perceptions of the scientific information in court, but it also improved their perceptions of the expert witness’s credibility, increased the weight assigned to the scientific information, and increased the weight assigned to the expert testimony. This effect was mediated by participants’ perceived similarity to the expert, supporting the theory behind the CK effect. These studies have important implications for the use of scientific information in court, which are discussed.
Journal Article
High-molecular weight DNA extraction, clean-up and size selection for long-read sequencing
Rapid advancements in long-read sequencing technologies have transformed read lengths from bps to Mbps, which has enabled chromosome-scale genome assemblies. However, read lengths are now becoming limited by the extraction of pure high-molecular weight DNA suitable for long-read sequencing, which is particularly challenging in plants and fungi. To overcome this, we present a protocol collection; high-molecular weight DNA extraction, clean-up and size selection for long-read sequencing. We optimised a gentle magnetic bead based high-molecular weight DNA extraction, which is presented here in detail. The protocol circumvents spin columns and high-centrifugation, to limit DNA fragmentation. The protocol is scalable based on tissue input, which can be used on many species of plants, fungi, reptiles and bacteria. It is also cost effective compared to kit-based protocols and hence applicable at scale in low resource settings. An optional sorbitol wash is listed and is highly recommended for plant and fungal tissues. To further remove any remaining contaminants such as phenols and polysaccharides, optional DNA clean-up and size selection strategies are given. This protocol collection is suitable for all common long-read sequencing platforms, such as technologies offered by PacBio and Oxford Nanopore. Using these protocols, sequencing on the Oxford Nanopore MinION can achieve read length N50 values of 30–50 kb, with reads exceeding 200 kb and outputs ranging from 15–30 Gbp. This has been routinely achieved with various plant, fungi, animal and bacteria samples.
Journal Article
Physical separation of haplotypes in dikaryons allows benchmarking of phasing accuracy in Nanopore and HiFi assemblies with Hi-C data
Background
Most animals and plants have more than one set of chromosomes and package these haplotypes into a single nucleus within each cell. In contrast, many fungal species carry multiple haploid nuclei per cell. Rust fungi are such species with two nuclei (karyons) that contain a full set of haploid chromosomes each. The physical separation of haplotypes in dikaryons means that, unlike in diploids, Hi-C chromatin contacts between haplotypes are false-positive signals.
Results
We generate the first chromosome-scale, fully-phased assembly for the dikaryotic leaf rust fungus
Puccinia triticina
and compare Nanopore MinION and PacBio HiFi sequence-based assemblies. We show that false-positive Hi-C contacts between haplotypes are predominantly caused by phase switches rather than by collapsed regions or Hi-C read mis-mappings. We introduce a method for phasing of dikaryotic genomes into the two haplotypes using Hi-C contact graphs, including a phase switch correction step. In the HiFi assembly, relatively few phase switches occur, and these are predominantly located at haplotig boundaries and can be readily corrected. In contrast, phase switches are widespread throughout the Nanopore assembly. We show that haploid genome read coverage of 30–40 times using HiFi sequencing is required for phasing of the leaf rust genome, with 0.7% heterozygosity, and that HiFi sequencing resolves genomic regions with low heterozygosity that are otherwise collapsed in the Nanopore assembly.
Conclusions
This first Hi-C based phasing pipeline for dikaryons and comparison of long-read sequencing technologies will inform future genome assembly and haplotype phasing projects in other non-haploid organisms.
Journal Article
Humidified and standard oxygen therapy in acute severe asthma in children (HUMOX): A pilot randomised controlled trial
Oxygen (O2) is a mainstay of treatment in acute severe asthma but how it is administered varies widely. The objectives were to examine whether a trial comparing humidified O2 to standard O2 in children is feasible, and specifically to obtain data on recruitment, tolerability and outcome measure stability.
Heated humidified, cold humidified and standard O2 treatments were compared for children (2-16 years) with acute severe asthma in a multi-centre, open, parallel, pilot randomised controlled trial (RCT). Multiple outcomes were assessed.
Of 258 children screened, 66 were randomised (heated humidified O2 n = 25; cold humidified O2 n = 21; standard O2 n = 20). Median (IQR) length of stay (hours) in hospital was 37.9 (29.1), 52 (35.4) and 49.1 (29.7) for standard, heated humidified and cold humidified respectively and time (hours) on O2 was 15.9 (9.4), 13.6 (14.9) and 13.1 (14.9) for the three groups respectively. The mean (standard deviation) time (hours) taken to step down nebulised to inhaled treatment was 5.6 (14.3), 35.1 (28.2) and 32.7 (20.1). Asthma Severity Score decreased in all three groups similarly, although missing data prevented complete analysis. Humidified O2 was least well tolerated with eight participants discontinuing their randomised treatment early. An important barrier to recruitment was research nurse availability.
Although, the results of this pilot study should not be extrapolated beyond the study sample and inferential conclusions should not be drawn from the results, this is the first RCT to compare humidified and standard O2 therapy in acute severe asthmatics of any age. These findings and accompanying screening data show that a large RCT of O2 therapy is feasible. However, challenges associated with randomisation and data collection should be addressed in any future trial design.
Journal Article
Cost-conscious generation of multiplexed short-read DNA libraries for whole-genome sequencing
Massively parallel, second-generation short-read DNA sequencing has become an integral tool in biology for genomic studies. Offering highly accurate base-pair resolution at the most competitive price, the technology has become widespread. However, high-throughput generation of multiplexed DNA libraries can be costly and cumbersome. Here, we present a cost-conscious protocol for generating multiplexed short-read DNA libraries using a bead-linked transposome from Illumina. We prepare libraries in high-throughput with small reaction volumes that use 1/50 th the amount of transposome compared to Illumina DNA Prep tagmentation protocols. By reducing transposome usage and optimising the protocol to circumvent magnetic bead-based clean-ups between steps, we reduce costs, labour time and DNA input requirements. Developing our own dual index primers further reduced costs and enables up to nine 96-well microplate combinations. This facilitates efficient usage of large-scale sequencing platforms, such as the Illumina NovaSeq 6000, which offers up to three terabases of sequencing per S4 flow cell. The protocol presented substantially reduces the cost per library by approximately 1/20 th compared to conventional Illumina methods.
Journal Article
Bladder Pain Syndrome: Rapid Evidence Review
Bladder pain syndrome is a chronic condition characterized by bladder pain associated with other urologic symptoms. It is a diagnosis of exclusion. Initial evaluation of suspected bladder pain syndrome includes a thorough history, physical examination, urinalysis, and urine culture, with cystoscopy reserved for further assessment. Symptom diaries help clarify the diagnosis, identify common triggers for flare-ups, and guide behavioral management strategies. Treatment begins with behavior and lifestyle modification and pelvic floor physical therapy. If this is inadequate, oral medications (eg, gabapentinoids, amitriptyline, antihistamines), intravesical instillation therapies, or procedural therapies (eg, neuromodulation) can be offered. Pain should be assessed at baseline and throughout the treatment course. Optimal treatment is multimodal, individualized, and multidisciplinary, frequently involving referral to urology or urogynecology specialists.
Journal Article
The impact of an electronic medical record nudge on reducing testing for hospital-onset Clostridioides difficile infection
To determine the effect of an electronic medical record (EMR) nudge at reducing total and inappropriate orders testing for hospital-onset Clostridioides difficile infection (HO-CDI).
An interrupted time series analysis of HO-CDI orders 2 years before and 2 years after the implementation of an EMR intervention designed to reduce inappropriate HO-CDI testing. Orders for C. difficile testing were considered inappropriate if the patient had received a laxative or stool softener in the previous 24 hours.
Four hospitals in an academic healthcare network.
All patients with a C. difficile order after hospital day 3.
Orders for C. difficile testing in patients administered a laxative or stool softener in <24 hours triggered an EMR alert defaulting to cancellation of the order (\"nudge\").
Of the 17,694 HO-CDI orders, 7% were inappropriate (8% prentervention vs 6% postintervention; P < .001). Monthly HO-CDI orders decreased by 21% postintervention (level-change rate ratio [RR], 0.79; 95% confidence interval [CI], 0.73-0.86), and the rate continued to decrease (postintervention trend change RR, 0.99; 95% CI, 0.98-1.00). The intervention was not associated with a level change in inappropriate HO-CDI orders (RR, 0.80; 95% CI, 0.61-1.05), but the postintervention inappropriate order rate decreased over time (RR, 0.95; 95% CI, 0.93-0.97).
An EMR nudge to minimize inappropriate ordering for C. difficile was effective at reducing HO-CDI orders, and likely contributed to decreasing the inappropriate HO-CDI order rate after the intervention.
Journal Article