Patterns of joint involvement in juvenile idiopathic arthritis and prediction of disease course: A prospective study with multilayer non-negative matrix factorization.

BACKGROUND: Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories. METHODS AND FINDINGS: We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom onset. Twenty-one patients had systemic arthritis, 300 oligoarthritis, 125 rheumatoid factor (RF)-negative polyarthritis, 16 RF-positive polyarthritis, 37 psoriatic arthritis, 78 enthesitis-related arthritis (ERA), and 63 undifferentiated arthritis. At diagnosis, we observed global hierarchical groups of co-involved joints. To characterize these patterns, we developed sparse multilayer non-negative matrix factorization (NMF). Model selection by internal bi-cross-validation identified seven joint patterns at presentation, to which all 640 discovery patients were assigned: pelvic girdle (57 patients), fingers (25), wrists (114), toes (48), ankles (106), knees (283), and indistinct (7). Patterns were distinct from clinical subtypes (P \u3c 0.001 by χ2 test) and reproducible through external data set validation on a 119-patient, prospectively collected independent validation cohort (reconstruction accuracy Q2 = 0.55 for patterns; 0.35 for groups). Some patients matched multiple patterns. To determine whether their disease outcomes differed, we further subdivided the 640 discovery patients into three subgroups by degree of localization-the percentage of their active joints aligning with their assigned pattern: localized (≥90%; 359 patients), partially localized (60%-90%; 124), or extended ( CONCLUSIONS: Multilayer NMF identified patterns of joint involvement that predicted disease trajectory in children with arthritis. Our hierarchical unsupervised approach identified a new clinical feature, degree of localization, which predicted outcomes in both cohorts. Detailed assessment of every joint is already part of every musculoskeletal exam for children with arthritis. Our study supports both the continued collection of detailed joint involvement and the inclusion of patterns and degrees of localization to stratify patients and inform treatment decisions. This will advance pediatric rheumatology from counting joints to realizing the potential of using data available from uncovering patterns of joint involvement

Shakeout in the Early Commercial Airframe Industry

The commercial airframe industry in the US experienced a shakeout from the early 1930s into the post‐Second World War period. Unlike shakeouts in automobiles, tyres, or televisions, the commercial airframe industry\u27s early life cycle was affected by external factors, particularly government demand. Using newly digitized data on all planes introduced in the commercial market between 1926 and 1965, we find that commercial airframe manufacturers with bomber contracts during the Second World War were more likely to have postwar market share than firms without such contracts, controlling for plane characteristics and other forms of government contracting. We attribute the effect of bomber contracts to advantages in R&D learning capacity acquired by firms with military airframe contracts. Despite low (or zero) initial presence in the commercial market, these learning capacity advantages allowed such firms to survive the early period of the shakeout, and later to thrive

LI Jianmin“ Silk Sutures: Trachea Surgery in Sixteenth-Century China

本文は、李建民「明代《外科正宗・救自刎断喉法》考釈」(『九州学林』32、香港城市大学中国文化中心、2013)の翻訳である。著者の李建民氏(台湾 中央研究院歴史語言研究所)は中国医学史を専門とし、著書に『死生之域-周秦漢脈学之源流』(2000)『生命史学-従医療看中国歴史』(2005)『旅行者的史学-中国医学史的旅行』(2009)『華佗隠蔵的手術-外科的中国医学史』(2011)等、また日本語による論文に「考古学上の発見と任脈学説の新認識」(荒川緑訳、『中国-社会と文化』18、2003)がある。本文は中医史のうちでも「手術史」という注目されることの少ない分野に焦点を当てたもので、その研究に当たっては、中医史の主流をなす内科的枠組からも、また西洋医学との安直な比較からも距離を置き、むしろ不連続でしばしば突発的でさえある諸事例をそれ自体として扱う「先例」分析法を適用すべきことを提唱する。なお紙幅の都合上、後記および注の一部を割愛した

Genetic architecture distinguishes systemic juvenile idiopathic arthritis from other forms of juvenile idiopathic arthritis: Clinical and therapeutic implications

Objectives Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA. Using genomic approaches, we sought to gain novel insights into the pathophysiology of sJIA and its relationship with other forms of JIA. Methods We performed a genome-wide association study of 770 children with sJIA collected in nine countries by the International Childhood Arthritis Genetics Consortium. Single nucleotide polymorphisms were tested for association with sJIA. Weighted genetic risk scores were used to compare the genetic architecture of sJIA with other JIA subtypes. Results The major histocompatibility complex locus and a locus on chromosome 1 each showed association with sJIA exceeding the threshold for genome-wide significance, while 23 other novel loci were suggestive of association with sJIA. Using a combination of genetic and statistical approaches, we found no evidence of shared genetic architecture between sJIA and other common JIA subtypes. Conclusions The lack of shared genetic risk factors between sJIA and other JIA subtypes supports the hypothesis that sJIA is a unique disease process and argues for a different classification framework. Research to improve sJIA therapy should target its unique genetics and specific pathophysiological pathways

Perceived and objective neighborhood support for outside of school physical activity in South African children.

The neighborhood environment has the potential to influence children's participation in physical activity. However, children's outdoor play is controlled by parents to a great extent. This study aimed to investigate whether parents' perceptions of the neighborhood environment and the objectively measured neighborhood environment were associated with children's moderate-to-vigorous intensity physical activity (MVPA) outside of school hours; and to determine if these perceptions and objective measures of the neighborhood environment differ between high and low socio-economic status (SES) groups.In total, 258 parents of 9-11 year-old children, recruited from the South African sample of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE), completed a questionnaire concerning the family and neighborhood environment. Objective measures of the environment were also obtained using Geographic Information Systems (GIS). Children wore an Actigraph (GT3X+) accelerometer for 7 days to measure levels of MVPA. Multilevel regression models were used to determine the association between the neighborhood environment and MVPA out of school hours.Parents' perceptions of the neighborhood physical activity facilities were positively associated with children's MVPA before school (β = 1.50 ± 0.51, p = 0.003). Objective measures of neighborhood safety and traffic risk were associated with children's after-school MVPA (β = -2.72 ± 1.35, p = 0.044 and β = -2.63 ± 1.26, p = 0.038, respectively). These associations were significant in the low SES group (β = -3.38 ± 1.65, p = 0.040 and β = -3.76 ± 1.61, p = 0.020, respectively), but unrelated to MVPA in the high SES group.This study found that several of the objective measures of the neighborhood environment were significantly associated with children's outside-of-school MVPA, while most of the parents' perceptions of the neighborhood environment were unrelated

"Potentialities or Possibilities": Towards Quantum Information Science?

The use of quantum concepts and formalisms in the information sciences is assessed through an analysis of published literature. Five categories are identified: use of loose analogies and metaphors between concepts in quantum physics and library/information science; use of quantum concepts and formalisms in information retrieval; use of quantum concepts and formalisms in studying meaning and concepts; quantum social science, in areas adjacent to information science; and the qualitative application of quantum concepts in the information disciplines. Quantum issues have led to demonstrable progress in information retrieval and semantic modelling, with less clear-cut progress elsewhere. Whether there may be a future “quantum turn” in the information sciences is debated, the implications of such a turn are considered, and a research agenda outlined

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial

Extent: 5p.Background: Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes. The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes. Methods/Design: Design: Multicentred randomised, controlled trial. Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies. Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice. Outcome assessors will be blinded to the allocated treatment group. Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age). Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed). Discussion This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.Jodie M Dodd, Deborah A Turnbull, Andrew J McPhee, Gary Wittert, Caroline A Crowther and Jeffrey S Robinso