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Biology subjects

Heywood, J.

Publications and source records attributed to Heywood, J..

2 recordsLinked to original sources

Segmenting accelerometer data from daily life with unsupervised machine learning

PurposeAccelerometers are increasingly used to obtain valuable descriptors of physical activity for health research. The cut-points approach to segment accelerometer data is widely used in physical activity research but requires resource expensive calibration studies and does not make it easy to explore the information that can be gained for a variety of raw data metrics. To address these limitations, we present a data-driven approach for segmenting and clustering the accelerometer data using unsupervised machine learning.\n\nMethodsThe data used came from five hundred fourteen-year-old participants from the Millennium cohort study who wore an accelerometer (GENEActiv) on their wrist on one weekday and one weekend day. A Hidden Semi-Markov Model (HSMM), configured to identify a maximum of ten behavioral states from five second averaged acceleration with and without addition of x, y, and z-angles, was used for segmenting and clustering of the data. A cut-points approach was used as comparison.\n\nResultsTime spent in behavioral states with or without angle metrics constituted eight and five principal components to reach 95% explained variance, respectively; in comparison four components were identified with the cut-points approach. In the HSMM with acceleration and angle as input, the distributions for acceleration in the states showed similar groupings as the cut-points categories, while more variety was seen in the distribution of angles.\n\nConclusionOur unsupervised classification approach learns a construct of human behavior based on the data it observes, without the need for resource expensive calibration studies, has the ability to combine multiple data metrics, and offers a higher dimensional description of physical behavior. States are interpretable from the distributions of observations and by their duration.

epidemiology

Targeting regulatory T cells with Interleukin-2 treatment in type 1 diabetes: a response-adaptive, non-randomised, open-label trial of repeat doses of Aldesleukin (DILfrequency)

BackgroundType 1 diabetes (T1D) results from loss of immune regulation leading to the development of autoimmunity to pancreatic beta-cells, involving autoreactive T effector cells (Teffs). Regulatory T cells (Tregs), that prevent autoimmunity, require Interleukin-2 (IL-2) for maintenance of immunosuppressive functions and, alterations in the IL-2 pathway predispose to T1D. Using an adaptive trial design we aimed to determine the optimal regimen of aldesleukin (recombinant human IL-2) to physiologically enhance Tregs while limiting expansion of autoreactive Teffs.\n\nMethodsDILfrequency is a single-center, non-randomised, open-label, response-adaptive study of participants aged 18 to 70 years with T1D. The initial learning phase allocated 12 participants to six different predefined dose-frequency regimens. Then, three cohorts of 8 participants were sequentially allocated dose-frequencies, based on repeated interim analyses of all accumulated trial data. The co-primary endpoints were percentage change in Tregs, Teffs and, CD25 ( subunit of the IL-2 receptor) expression by Tregs, from baseline to steady state. Trial registration ISRCTN40319192 and ClinicalTrials.gov (NCT02265809).\n\nFindings115 participants were assessed between November 17th 2014 and May 22nd 2016, 38 participants were enrolled with 36 completing treatment. The optimal regimen to maintain a steady state increase in Tregs of 30% and CD25 expression of 25% without Teff expansion is 0.26 x 106 IU/m2 (95% CI (-0.007 to 0.485)) every 3 days (1.3 to 4.4). Tregs and CD25 were dose-frequency responsive, while Teffs were not. The commonest adverse event was injection site reaction (464/694 events), with a single participant developing transient eosinophilia at the highest dose (0.47 x 106 IU/m2).\n\nInterpretationThis response-adaptive trial defined a well-tolerated aldesleukin regimen that specifically induces Treg expansion that can now be trialled to treat T1D.\n\nFundingSir Jules Thorn Trust, Wellcome, JDRF, SNSF, NIHR

clinical trials