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Designing for longevity and neutrality: Investigating how the Swedish children’s clothing industry implements circular economy principles
No full textAs research has well established, the fashion industry has a significant and growing waste problem. In response, experts argue that our clothing needs to have a longer life. However, not all items of clothing can be used for a long period of time. Children’s clothing, for example, can quickly become obsolete, creating a waste issue. To explore this issue further, we examine the Swedish children’s wear market and how designing for the circular economy can address this market segment’s unique sustainability challenges. Rather than centering on a consumer perspective, we investigate the role of design in supporting the transition to a more circular children’s clothing industry. As a key contribution, this article demonstrates that there are more circular design strategies available than prior research has explicitly mentioned. In particular, we show how design for longevity and design for neutrality can help to overcome some of the sustainability challenges facing the industry
Defining Trajectories of Response in Psoriasis Patients Treated with Biologic Therapies
No full textBACKGROUND: The effectiveness and cost-effectiveness of biologic therapies for psoriasis are significantly compromised by variable treatment responses. Thus, more precise management of psoriasis is needed.OBJECTIVES: We aim to identify subgroups of psoriasis patients treated with biologic therapies, based on changes in their disease activity over time, that may better inform patient management.METHODS: Here we apply latent class mixed modelling, to identify trajectory-based patient subgroups from longitudinal, routine clinical data on disease severity, as measured by the Psoriasis Area and Severity Index (PASI), from 3546 patients in the British Association of Dermatologists Biologics and Immunomodulators Register, as well as in an independent cohort of 2889 subjects pooled across four clinical trials. RESULTS: We discovered four, discrete classes of global response trajectories, each characterised in terms of time to response, size of effect and relapse. Each class was associated with differing clinical characteristics, e.g. Body Mass Index, baseline PASI, and prevalence of different manifestations. Our results were verified in a second cohort of clinical trials subjects, where similar trajectories following initiation of biologic therapy were identified. Further, we found differential associations of the genetic marker HLA-C*06:02 between our registry-identified trajectories. CONCLUSION: These subgroups, defined by change in disease over time, may be indicative of distinct endotypes driven by different biological mechanisms and may help inform the management of patients with psoriasis. Future work will aim to further delineate these mechanisms by extensively characterising the subgroups with additional molecular and pharmacological data. <br/
High penetrance of myeloid neoplasia with diverse clinical and cytogenetic features in three siblings with a familial GATA2 deficiency
No full textPathogenic germ-line variants in GATA2 (GATA2 deficiency) can cause childhood myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and can be associated with distinct clinical syndromic features. However, penetrance and genotype-phenotype correlations are incompletely understood. Here we report on the clinically diverse features of three siblings affected by GATA2c.1021_1031del over an 18-year period, all initially presenting in childhood and adolescence with MDS and AML with monosomy 7 (-7), and one also with monosomy trisomy 8 (+8).The siblings inherited a GATA2c.1021_1031del from their father who remains asymptomatic in his sixth decade. The two younger sisters are well after unrelated haematopoietic stem cell transplantation (HSCT), while the first boy died of severe chronic lung disease after sibling HSCT from his youngest sister, who subsequently also developed GATA2-deficiency associated MDS. This family illustrates high penetrance with variable genotype/phenotype correlation within one generation with GATA2-deficiency. We surmise that the lung disease post sibling HSCT was alsocaused by the GATA2-deficiency. The experience with this family underlines the necessity for GATA2 analysis in all apparently sporadic childhood and teenage MDS and AML with -7 or +8 also in the absence of a family history or other clinical features, and rigorous genetic testing in siblings. Moreover, our findings support the arguments for pre-emptive HSCT in variant-carrying siblings
Associations of loneliness and social isolation with physical and mental health among adolescents and young adults
No full textAims: The present study investigates whether loneliness and social isolation are associated with poor physical and mental health among adolescents and young adults and whether age and gender play a role in the associations of loneliness and social isolation with mental and physical health. Methods: This study used cross-sectional self-report data from the 2017 Danish Health and Morbidity Surveys entitled "How are you?" (n = 19,890, M = 22.6 years). Results: Logistic regression analyses showed that loneliness and social isolation were independently associated with poor physical and mental health. Loneliness was associated with increased odds of asthma, migraine, osteoarthritis, rheumatoid arthritis, hypertension, slipped disc/back pain, tinnitus, long-term mental illness, depressive symptomatology, anxiety symptomatology and alcohol problems. Social isolation was associated with decreased odds of having migraine, osteoarthritis and alcohol problems, and an increased risk of long-term mental illness and depressive symptomatology. Small age and gender differences were detected. Conclusions: In adolescents and young adults, loneliness and social isolation were associated with poor mental health and loneliness with poor physical health. These findings highlight the need for targeted prevention and intervention initiatives to alleviate loneliness and social isolation
Diagrammatic Summaries for Neural Architectures
No full textThis paper advocates for diagrammatic summary publications for machine learning system architecture papers. We review existing diagram-centric scholarly practices, and summarise relevant studies on neural network system architecture diagrams. We subsequently propose three opportunities: Diagram guidelines, diagrammatic system summary publications, and the community creation of a formal diagram standards, which could be integrated with existing LaTeX + PDF publication processes
Modelling finger propagation in elasto-rigid channels
No full textWe conduct a theoretical study of a two-phase-fluid-structure interaction problem in which air is driven at constant volume flux into a liquid-filled Hele-Shaw channel whose upper boundary is an elastic sheet. A depth-averaged model in the frame of reference of the advancing air-liquid interface is used to investigate the steady and unsteady interface propagation modes via numerical simulation. In slightly collapsed channels, the steadily-propagating interface adopts a shape that is similar to the classic Saman{ Taylor finger in rigid Hele-Shaw cells. As the level of initial collapse increases the induced gradients in channel depth alter the morphology of the propagating finger and promote a variety of instabilities from tip-splitting to small-scale fingering on the curved interface, in qualitative agreement with experiments. The model has a complex solution structure with a wide range of stable and unstable, steady and time-periodic modes, many of which have similar driving pressures. We find good quantitative agreement between our model and the experimental data of Ducloue et al. (J. Fluid Mech. vol. 819, 2017, p 121) for the finger width, sheet profile and finger pressure, provided that corrections to account for the presence of liquid films on the upper and lower walls of the channel are included in the model
Relationship Between Metabolic Toxicity and Efficacy of Everolimus in Patients With Neuroendocrine Tumors: A Pooled Analysis From the Randomized, Phase 3 RADIANT-3 and RADIANT-4 Trials
No full textBACKGROUND: Hyperglycemia and hypercholesterolemia are class effects of mTOR inhibitors such as everolimus. This post hoc pooled analysis assessed the potential impact of these events on the efficacy of everolimus.METHODS: Patients with advanced, low-, or intermediate-grade pancreatic, GI, or lung NETs received either everolimus 10 mg/day orally or placebo in the RADIANT-3 and RADIANT-4 trials. A landmark PFS analysis by central review was performed on patients treated for at least 16 weeks (N = 308 [n = 200/412]) and according to the occurrence of any-grade AEs within this treatment period.RESULTS: The overall PFS with everolimus from the pooled analysis was 11.4 months (95% CI, 11.01-13.93 months), consistent with the findings of RADIANT-3 and RADIANT-4. Overall, 19.1% and 9.8% of patients in RADIANT-3 and 11.9% and 6.4% of patients in RADIANT-4 developed any-grade (regardless of study drug) hyperglycemia and hypercholesterolemia, respectively. The duration of everolimus exposure was longer in patients who developed these AEs vs patients without these AEs. Overall, 308 patients were exposed to treatment for at least 16 weeks (hyperglycemia [n = 39 of 269] and hypercholesterolemia [n = 20 of 288]). No association was observed between the development of these AEs and PFS (with/without hyperglycemia [18.8 months/14.1 months] and hypercholesterolemia [14.1 months/14.8 months]. CONCLUSIONS: Although limitations apply because of the small number of AEs observed, there was no significant impact of these AEs on PFS, suggesting a similar efficacy in the presence or absence of these events.<br/
Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines
No full textWe report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) amacrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product. The two molecular machines participate in the synthesis of a product that is beyond the capability ofindividual small-molecule machines, in a manner reminiscent of the ligation and post-translational modification of proteins in biology
The fetal umbilical artery Doppler as a tool for universal third trimester screening: a systematic review and meta-analysis of diagnostic test accuracy.
No full textThe objective of this study was to investigate the accuracy of universal third trimester umbilical artery (UA) Doppler to predict adverse pregnancy outcome at term. We searched Medline, EMBASE, the Cochrane library and ClinicalTrials.gov from inception to October 2020 and we also analyzed previously unpublished data from a prospective cohort study of nulliparous women, the Pregnancy Outcome Prediction (POP) study. We included studies that performed a third-trimester ultrasound scan in unselected, low or mixed risk populations, excluding studies which only included high risk pregnancies. Meta-analysis was performed using the hierarchal summary receiver operating characteristic curve (HSROC) analysis and bivariate logit-normal models. We identified 13 studies (including the POP study) involving 67,764 pregnancies which met our inclusion criteria. The overall quality was variable and only six studies (N= 5777 patients) blinded clinicians to the UA Doppler result. The summary sensitivity and positive likelihood ratio (LR) for small for gestational age (SGA; birthweight <10th centile) were 21.7% (95% CI 13.2-33.6%) and 2.65 (95% CI 1.89-3.72) respectively. The summary positive LR for NICU admission and metabolic acidosis were 1.35 (95% CI 0.93-1.97) and 1.34 (95% CI 0.86-2.08) respectively. The results were similar in the POP study: associations with SGA (positive LR 2.66 [95% CI 2.11-3.36]) and severe SGA (birthweight <3rd centile; positive LR 3.27 [95% CI 2.29-4.68]) but no statistically significant association with neonatal morbidity. We conclude that third trimester UA Doppler has moderate predictive accuracy for small for gestational age but not for indicators of neonatal morbidity in unselected and low risk pregnancies
Mechanisms underlying the association of chronic obstructive pulmonary disease with heart failure
No full textBackground: Chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF), independent of shared risk factors. The underlying pathophysiological mechanism is unknown. Objectives: To determine why COPD is associated with HF. Specifically, whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalisation for HF and death in COPD and whether COPD and smoking are associated with myocardial inflammation. Methods: A prospective, multicentre, longitudinal cohort study of 572 patients undergoing cardiac magnetic resonance imaging (MRI), including 450 patients with COPD and 122 age- and sex-matched patients, with median (interquartile range) 726 (492-1160) day follow-up. Multivariable analysis examined the relationship between COPD and myocardial fibrosis, measured using cardiac MRI. Cox regression examined the relationship between myocardial fibrosis and outcomes; primary endpoint: composite of hospitalisation for HF or all-cause mortality; secondary endpoints: hospitalisation for HF and all-cause mortality. Fifteen patients with COPD, 15 current smokers and 15 healthy volunteers underwent evaluation for myocardial inflammation, including ultrasmall superparamagnetic particles of iron oxide MRI. Results: COPD was independently associated with myocardial fibrosis (p<0.001). Myocardial fibrosis was independently associated with the primary outcome (hazard ratio (HR) 1.14; 95% confidence interval 1.08-1.20; p<0.001), hospitalisation for HF (HR 1.25 [1.14-1.36]); p<0.001) and all-cause mortality. Myocardial fibrosis was associated with outcome measurements more strongly than any other variable. Acute and stable COPD were associated with myocardial inflammation. Conclusions: The association between COPD, myocardial inflammation and myocardial fibrosis, and the independent prognostic value of myocardial fibrosis, elucidate a potential pathophysiological link between COPD and HF