Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST—Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial

BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab. METHODS: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg). DISCUSSION: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 201

A complete transition to clean household energy can save one–quarter of the healthy life lost to particulate matter pollution exposure in India

Exposure to fine particulate matter (PM _2.5 ) is a leading contributor to the disease burden in India, largely due to widespread household solid fuel use. The transition from solid to clean fuels in households has the potential to substantially improve public health. India has implemented large initiatives to promote clean fuel access, but how these initiatives will reduce PM _2.5 exposure and the associated health benefits have not yet been established. We quantified the impacts of a transition of household energy from solid fuel use to liquefied petroleum gas (LPG) on public health in India from ambient and household PM _2.5 exposure. We estimate that the transition to LPG would reduce ambient PM _2.5 concentrations by 25%. Reduced exposure to total PM _2.5 results in a 29% reduction in the loss of healthy life, preventing 348 000 (95% uncertainty interval, UI: 284 000–373 000) premature mortalities every year. Achieving these benefits requires a complete transition to LPG. If access to LPG is restricted to within 15 km of urban centres, then the health benefits of the clean fuel transition are reduced by 50%. If half of original solid fuel users continue to use solid fuels in addition to LPG, then the health benefits of the clean fuel transition are reduced by 75%. As the exposure–outcome associations are non–linear, it is critical for air pollution studies to consider the disease burden attributed to total PM _2.5 exposure, and not only the portion attributed to either ambient or household PM _2.5 exposure. Our work shows that a transition to clean household energy can substantially improve public health in India, however, these large public health benefits are dependent on the complete transition to clean fuels for all

Thermodynamics of an ideal generalized gas:II Means of order α\alpha

The property that power means are monotonically increasing functions of their order is shown to be the basis of the second laws not only for processes involving heat conduction but also for processes involving deformations. In an $L$-potentail equilibration the final state will be one of maximum entropy, while in an entropy equilibrium the final state will be one of minimum $L$. A metric space is connected with the power means, and the distance between means of different order is related to the Carnot efficiency. In the ideal classical gas limit, the average change in the entropy is shown to be proportional to the difference between the Shannon and R\'enyi entropies for nonextensive systems that are multifractal in nature. The $L$-potential, like the internal energy, is a Schur convex function of the empirical temperature, which satisfies Jensen's inequality, and serves as a measure of the tendency to uniformity in processes involving pure thermal conduction.Comment: 8 page

Optimizing outcomes for patients with severe haemophilia A

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73864/1/j.1365-2516.2007.01552.x.pd

Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema

<p>Abstract</p> <p>Background</p> <p>It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8⁺T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8⁺T lymphocytes of emphysematous smokers who show evidence of systemic inflammation will have higher expression of cytotoxic molecules.</p> <p>Methods</p> <p>We assessed parameters of systemic inflammation in normal individuals (smokers or non-smokers) and in emphysematous subjects with an active smoking history by measuring serum interleukine-6, C-reactive protein, and tumor necrosis factor. Expression of perforin, granzyme B, and FasL protein by CD8⁺T lymphocytes, CD4⁺T lymphocytes, and natural killer cells were assessed by flow cytometry while perforin, granzyme B, and FasL mRNA expression were measured on purified systemic CD8⁺T lymphocytes by real-time PCR.</p> <p>Results</p> <p>Emphysematous smokers had higher levels of serum interleukine-6 than normal subjects. Even with the presence of systemic inflammation in emphysematous smokers, the percentage of peripheral CD8⁺T lymphocytes, CD4⁺T lymphocytes, and NK cells expressing perforin and granzyme B protein was not different between the three groups.</p> <p>Conclusion</p> <p>Despite evidence of systemic inflammation, peripheral T lymphocytes of emphysematous smokers did not show higher levels of cytotoxic markers, suggesting that increase of activated T lymphocytes in the emphysematous lung may be due to either activation in the lung or specific peripheral recruitment.</p

Changes in lower limb rotation after soft tissue surgery in spastic diplegia: 3-dimensional gait analysis in 28 children

Background and purpose Rotational osteotomies are usually necessary to correct pronounced rotational deformities in ambulant children with cerebral palsy. The effects of soft tissue surgery on such deformities are unclear. In this retrospective study, we determined whether multilevel soft tissue surgery, performed to correct deformities in the sagittal plane, would also have an effect on rotational parameters

Case report and summary of literature: giant perineal keloids treated with post-excisional radiotherapy

BACKGROUND: Keloids are common benign tumors of the dermis, typically arising after insult to the skin. While typically only impinging on cosmesis, large or recurrent keloids may require therapeutic intervention. While no single standardized treatment course has been established, several series report excellent outcomes for keloids with post-surgery radiation therapy. CASE PRESENTATION: We present a patient with a history of recurrent keloids arising in the absence of an ascribed trauma and a maternal familial history of keloid formation, whose physical examination several large perineal keloids of 6-20 cm in the largest dimension. The patient was treated with surgical extirpation and adjuvant radiation therapy. Radiotherapy was delivered to the scar bed to a total dose of 22 Gy over 11 daily fractions. Acute radiotherapy toxicity necessitated a treatment break due to RTOG Grade III acute toxicity (moderate ulceration and skin breakdown) which resolved rapidly during a 3-day treatment break. The patient demonstrated local control and has remained free of local recurrence for more than 2 years. CONCLUSION: Radiotherapy for keloids represents a safe and effective option for post-surgical keloid therapy, especially for patients with bulky or recurrent disease

Patterns of Reproductive Isolation in Toads

Understanding the general features of speciation is an important goal in evolutionary biology, and despite significant progress, several unresolved questions remain. We analyzed an extensive comparative dataset consisting of more than 1900 crosses between 92 species of toads to infer patterns of reproductive isolation. This unique dataset provides an opportunity to examine the strength of reproductive isolation, the development and sex ratios of hybrid offspring, patterns of fertility and infertility, and polyploidization in hybrids all in the context of genetic divergence between parental species. We found that the strength of intrinsic postzygotic isolation increases with genetic divergence, but relatively high levels of divergence are necessary before reproductive isolation is complete in toads. Fertilization rates were not correlated to genetic divergence, but hatching success, the number of larvae produced, and the percentage of tadpoles reaching metamorphosis were all inversely related with genetic divergence. Hybrids between species with lower levels of divergence developed to metamorphosis, while hybrids with higher levels of divergence stopped developing in gastrula and larval stages. Sex ratios of hybrid offspring were biased towards males in 70% of crosses and biased towards females in 30% of crosses. Hybrid females from crosses between closely related species were completely fertile, while approximately half (53%) of hybrid males were sterile, with sterility predicted by genetic divergence. The degree of abnormal ploidy in hybrids was positively related to genetic divergence between parental species, but surprisingly, polyploidization had no effect on patterns of asymmetrical inviability. We discuss explanations for these patterns, including the role of Haldane's rule in toads and anurans in general, and suggest mechanisms generating patterns of reproductive isolation in anurans