An Evaluation Framework for Personalization Strategy Experiment Designs

Online Controlled Experiments (OCEs) are the gold standard in evaluating the effectiveness of changes to websites. An important type of OCE evaluates different personalization strategies, which present challenges in low test power and lack of full control in group assignment. We argue that getting the right experiment setup -- the allocation of users to treatment/analysis groups -- should take precedence of post-hoc variance reduction techniques in order to enable the scaling of the number of experiments. We present an evaluation framework that, along with a few simple rule of thumbs, allow experimenters to quickly compare which experiment setup will lead to the highest probability of detecting a treatment effect under their particular circumstance.Comment: Presented in the AdKDD 2020 workshop, in conjunction with The 26th ACM SIGKDD Conference on Knowledge Discovery and Data Mining, KDD 2020. Main paper: 7 pages, 2 figures, 2 tables, Supplementary document: 6 page

Magma fragmentation:a perspective on emerging topics and future directions

AbstractThe breaking apart of magma into fragments is intimately related to the eruptive style and thus the nature and footprint of volcanic hazards. The size and shape distributions of the fragments, in turn, affect the efficiency of heat transfer within pyroclastic plumes and currents and the settling velocity, and so the residence time, of particles in the atmosphere. Fundamental work relating the glass transition to the fragmentation of magmas remains at the heart of conceptual and numerical models of volcanic eruptions. Current fragmentation criteria, however, do not predict the sizes and shapes of the resulting fragments, or fully account for the multiphase nature of magmas or ways in which magma can break in a fluidal manner or by thermal stress. The pulsatory, non-steady state nature of some eruptions, and related interactions with these fragmentation criteria, also requires further investigation. Here, we briefly review some recent advances in the field of magma fragmentation and provide a perspective on how integrated field, experimental and numerical modelling studies can address key outstanding challenges.</jats:p

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells.

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets

Thy-1 interaction with Fas in lipid rafts regulates fibroblast apoptosis and lung injury resolution.

Thy-1-negative lung fibroblasts are resistant to apoptosis. The mechanisms governing this process and its relevance to fibrotic remodeling remain poorly understood. By using either sorted or transfected lung fibroblasts, we found that Thy-1 expression is associated with downregulation of anti-apoptotic molecules Bcl-2 and Bcl-xL, as well as increased levels of cleaved caspase-9. Addition of rhFasL and staurosporine, well-known apoptosis inducers, caused significantly increased cleaved caspase-3, -8, and PARP in Thy-1-transfected cells. Furthermore, rhFasL induced Fas translocation into lipid rafts and its colocalization with Thy-1. These in vitro results indicate that Thy-1, in a manner dependent upon its glycophosphatidylinositol anchor and lipid raft localization, regulates apoptosis in lung fibroblasts via Fas-, Bcl-, and caspase-dependent pathways. In vivo, Thy-1 deficient (Thy1-/-) mice displayed persistence of myofibroblasts in the resolution phase of bleomycin-induced fibrosis, associated with accumulation of collagen and failure of lung fibrosis resolution. Apoptosis of myofibroblasts is decreased in Thy1-/- mice in the resolution phase. Collectively, these findings provide new evidence regarding the role and mechanisms of Thy-1 in initiating myofibroblast apoptosis that heralds the termination of the reparative response to bleomycin-induced lung injury. Understanding the mechanisms regulating fibroblast survival/apoptosis should lead to novel therapeutic interventions for lung fibrosis

Tests of pattern separation and pattern completion in humans - a systematic review

OBJECTIVE: To systematically review the characteristics, validity and outcome measures of tasks that have been described in the literature as assessing pattern separation and pattern completion in humans. METHODS: Electronic databases were searched for articles. Parameters for task validity were obtained from two reviews that described optimal task design factors to evaluate pattern separation and pattern completion processes. These were that pattern separation should be tested during an encoding task using abstract, never-before-seen visual stimuli, and pattern completion during a retrieval task using partial cues; parametric alteration of the degree of interference of stimuli or degradation of cues should be used to generate a corresponding gradient in behavioral output; studies should explicitly identify the specific memory domain under investigation (sensory/perceptual, temporal, spatial, affect, response, or language) and account for the contribution of other potential attributes involved in performance of the task. A systematic, qualitative assessment of validity in relation to these parameters was performed, along with a review of general validity and task outcome measures. RESULTS: Sixty-two studies were included. The majority of studies investigated pattern separation and most tasks were performed on young, healthy adults. Pattern separation and pattern completion were most frequently tested during a retrieval task using familiar or recognizable visual stimuli and cues. Not all studies parametrically altered the degree of stimulus interference or cue degradation, or controlled for potential confounding factors. CONCLUSION: This review found evidence that some of the parameters for task validity have been followed in some human studies of pattern separation and pattern completion, but no study was judged to have adequately met all the parameters for task validity. The contribution of these parameters and other task design factors towards an optimal behavioral paradigm is discussed and recommendations for future research are made. This article is protected by copyright. All rights reserved

APC-targeted proinsulin expression inactivates insulin-specific memory CD8+ T cells in NOD mice

Type 1 diabetes (T1D) results from T-cell-mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β-cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β-cell destructive effector and memory T-cell responses has the potential to prevent disease progression and recurrence. Targeting antigen expression to antigen-presenting cells inactivates cognate CD8+ effector and memory T-cell responses and has therapeutic potential. Here we investigated this in the context of insulin-specific responses in the non-obese diabetic mouse where genetic immune tolerance defects could impact on therapeutic tolerance induction. Insulin-specific CD8+ memory T cells transferred to mice expressing proinsulin in antigen-presenting cells proliferated in response to transgenically expressed proinsulin and the majority were rapidly deleted. A small proportion of transferred insulin-specific Tmem remained undeleted and these were antigen-unresponsive, exhibited reduced T cell receptor (TCR) expression and H-2Kd/insB15-23 tetramer binding and expressed co-inhibitory molecules. Expression of proinsulin in antigen-presenting cells also abolished the diabetogenic capacity of CD8+ effector T cells. Therefore, destructive insulin-specific CD8+ T cells are effectively inactivated by enforced proinsulin expression despite tolerance defects that exist in diabetes-prone NOD mice. These findings have important implications in developing immunotherapeutic approaches to T1D and other T-cell-mediated autoimmune diseases

Development and delivery of an exercise programme for falls prevention: the Prevention of Falls Injury Trial (PreFIT)

This paper describes the development and implementation of an exercise intervention to prevent falls within The Prevention of Fall Injury Trial (PreFIT), which is a large multi-centred randomised controlled trial based in the UK National Health Service (NHS).Using the template for intervention description and replication (TIDieR) checklist, to describe the rationale and processes for treatment selection and delivery of the PreFIT exercise intervention.Based on the results of a validated falls and balance survey, participants were eligible for the exercise intervention if they were at moderate or high risk of falling.Intervention development was informed using the current evidence base, published guidelines, and pre-existing surveys of clinical practice, a pilot study and consensus work with therapists and practitioners. The exercise programme targets lower limb strength and balance, which are known, modifiable risk factors for falling. Treatment was individually tailored and progressive, with seven recommended contacts over a six-month period. Clinical Trials Registry (ISCTRN 71002650)

17β-Estradiol inhibits proliferation and migration of human vascular smooth muscle cells: similar effects in cells from postmenopausal females and in males

Objectives: Cardiovascular disease is rare in premenopausal women, but increases after the menopause when hormone replacement therapy reduces coronary events. Vascular smooth muscle cell (SMC) proliferation and migration occur in atherosclerosis, restenosis and venous graft disease. We studied the effects of 17β-estradiol on SMC proliferation and migration. Methods: SMC were cultured from saphenous veins of postmenopausal women and age-matched men. Cell growth was determined by 3H-thymidine incorporation and cell counting. Migration of SMC was assessed in 4-well chambers. SMC were seeded in one corner and PDGF-BB in filter paper glued onto the opposite wall. Results: PDGF-BB (5 ng/ml for 24 h) similarly stimulated 3H-thymidine incorporation in female (511 ± 57%; n = 8) and male (528 ± 62%; n = 12) SMC. This was reduced by 17β-estradiol (10−8-10−6 M; female 313 ± 52%; male 337 ± 54%; P < 0.05). PDGF-BB increased the number of SMC (P < 0.0001 at 10 days) obtained from females (153 ± 3%; n = 5) and males (150 ± 4%; n = 5), which was inhibited by 17 β-estradiol (10−6 M; female 134 ± 7%; male 128 ± 5%; P < 0.05). Similar results were obtained with basic fibroblast growth factor. In contrast to 17β-estradiol, another steroid (dexamethasone) had no effects on 3H-thymidine incorporation in these cells stimulated with PDGF-BB. PDGF-BB (0.01-1 ng) stimulated SMC migration (P < 0.05) which was inhibited by 17β-estradiol (10−10-10−6 M; n = 5; P < 0.005). Conclusion: 17β-Estradiol inhibits growth-factor-induced SMC proliferation and migration regardless of gender. These effects of 17β-estradiol may contribute to its cardiovascular protective properties in postmenopausal women during replacement therap