Beyond spatial and temporal averages: ecological responses to extreme events may be exacerbated by local disturbances

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Genetic alterations in lymphoblastic leukaemia / lymphoma – a practical guide to WHO HAEM5

\ua9 2024 the author(s), published by De Gruyter.We present a practical guide for analyzing the genetic aspects of lymphoblastic leukaemia/lymphoma according to the 5th edition of the World Health Organization (WHO) classification of haematolymphoid neoplasms (WHO-HAEM5) issued in 2024. The WHO-HAEM5 acknowledges the increasing importance of genetics in the diagnosis of lymphoid neoplasia. Classification is based on the established genetic subtypes according to cell lineage, with precursor cell neoplasms followed by mature malignancies. This guide describes those genetic abnormalities in acute precursor B- and T-cell neoplasms required for risk stratification, and for treatment, providing diagnostic algorithms under the headings of ‘essential’ and ‘desirable’ diagnostic criteria

Sequential Extensions of Causal and Evidential Decision Theory

Moving beyond the dualistic view in AI where agent and environment are separated incurs new challenges for decision making, as calculation of expected utility is no longer straightforward. The non-dualistic decision theory literature is split between causal decision theory and evidential decision theory. We extend these decision algorithms to the sequential setting where the agent alternates between taking actions and observing their consequences. We find that evidential decision theory has two natural extensions while causal decision theory only has one.Comment: ADT 201

The potential health impact of restricting less-healthy food and beverage advertising on UK television between 05.30 and 21.00 hours: A modelling study

BACKGROUND: Restrictions on the advertising of less-healthy foods and beverages is seen as one measure to tackle childhood obesity and is under active consideration by the UK government. Whilst evidence increasingly links this advertising to excess calorie intake, understanding of the potential impact of advertising restrictions on population health is limited. METHODS AND FINDINGS: We used a proportional multi-state life table model to estimate the health impact of prohibiting the advertising of food and beverages high in fat, sugar, and salt (HFSS) from 05.30 hours to 21.00 hours (5:30 AM to 9:00 PM) on television in the UK. We used the following data to parameterise the model: children's exposure to HFSS advertising from AC Nielsen and Broadcasters' Audience Research Board (2015); effect of less-healthy food advertising on acute caloric intake in children from a published meta-analysis; population numbers and all-cause mortality rates from the Human Mortality Database for the UK (2015); body mass index distribution from the Health Survey for England (2016); disability weights for estimating disability-adjusted life years (DALYs) from the Global Burden of Disease Study; and healthcare costs from NHS England programme budgeting data. The main outcome measures were change in the percentage of the children (aged 5-17 years) with obesity defined using the International Obesity Task Force cut-points, and change in health status (DALYs). Monte Carlo analyses was used to estimate 95% uncertainty intervals (UIs). We estimate that if all HFSS advertising between 05.30 hours and 21.00 hours was withdrawn, UK children (n = 13,729,000), would see on average 1.5 fewer HFSS adverts per day and decrease caloric intake by 9.1 kcal (95% UI 0.5-17.7 kcal), which would reduce the number of children (aged 5-17 years) with obesity by 4.6% (95% UI 1.4%-9.5%) and with overweight (including obesity) by 3.6% (95% UI 1.1%-7.4%) This is equivalent to 40,000 (95% UI 12,000-81,000) fewer UK children with obesity, and 120,000 (95% UI 34,000-240,000) fewer with overweight. For children alive in 2015 (n = 13,729,000), this would avert 240,000 (95% UI 65,000-530,000) DALYs across their lifetime (i.e., followed from 2015 through to death), and result in a health-related net monetary benefit of £7.4 billion (95% UI £2.0 billion-£16 billion) to society. Under a scenario where all HFSS advertising is displaced to after 21.00 hours, rather than withdrawn, we estimate that the benefits would be reduced by around two-thirds. This is a modelling study and subject to uncertainty; we cannot fully and accurately account for all of the factors that would affect the impact of this policy if implemented. Whilst randomised trials show that children exposed to less-healthy food advertising consume more calories, there is uncertainty about the nature of the dose-response relationship between HFSS advertising and calorie intake. CONCLUSIONS: Our results show that HFSS television advertising restrictions between 05.30 hours and 21.00 hours in the UK could make a meaningful contribution to reducing childhood obesity. We estimate that the impact on childhood obesity of this policy may be reduced by around two-thirds if adverts are displaced to after 21.00 hours rather than being withdrawn

Fusion of green fluorescent protein to the C-terminus of granulysin alters its intracellular localization in comparison to the native molecule

The engineering of green fluorescent protein (GFP) fusion constructs in order to visibly tag a protein of interest has become a commonly used cell biology technique. Although caveats to this approach are obvious, literature reports in which the chimeric molecule behaves differently than the native molecule are scant. This brief report describes one such case. Granulysin, a small lytic and antimicrobial protein produced by cytotoxic lymphocytes, traffics to the regulated secretory system and is subsequently released from cells upon proper stimulus. In an attempt to elucidate mechanisms by which it accumulates in and is released from cytolytic granules, GFP was fused to the C-terminus of granulysin and expressed in an NK cell line. A control construct expressing the native protein was similarly expressed. The data demonstrate that, while the fusion protein is expressed and secreted, its subcellular localization is altered in comparison to native granulysin. Thus, the addition of GFP to the C-terminus of granulysin obscures the signal(s) that cytotoxic lymphocytes use to sort it to the regulated secretory pathway despite its normal biosynthesis and secretion. This example is offered as a cautionary account for other researchers who contemplate using this technology

MMS observations of electron-scale filamentary currents in the reconnection exhaust and near the X line

© 2016. American Geophysical Union. All Rights Reserved.We report Magnetospheric Multiscale observations of macroscopic and electron-scale current layers in asymmetric reconnection. By intercomparing plasma, magnetic, and electric field data at multiple crossings of a reconnecting magnetopause on 22 October 2015, when the average interspacecraft separation was ~10km, we demonstrate that the ion and electron moments are sufficiently accurate to provide reliable current density measurements at 30ms cadence. These measurements, which resolve current layers narrower than the interspacecraft separation, reveal electron-scale filamentary Hall currents and electron vorticity within the reconnection exhaust far downstream of the X line and even in the magnetosheath. Slightly downstream of the X line, intense (up to 3μA/m2) electron currents, a super-Alfvénic outflowing electron jet, and nongyrotropic crescent shape electron distributions were observed deep inside the ion-scale magnetopause current sheet and embedded in the ion diffusion region. These characteristics are similar to those attributed to the electron dissipation/diffusion region around the X line

The mass distribution of the unusual merging cluster Abell 2146 from strong lensing

Abell 2146 consists of two galaxy clusters that have recently collided close to the plane of the sky, and it is unique in showing two large shocks on $\textit{Chandra X-ray Observatory}$ images. With an early stage merger, shortly after first core passage, one would expect the cluster galaxies and the dark matter to be leading the X-ray emitting plasma. In this regard, the cluster Abell 2146-A is very unusual in that the X-ray cool core appears to lead, rather than lag, the brightest cluster galaxy (BCG) in their trajectories. Here we present a strong-lensing analysis of multiple-image systems identified on $\textit{Hubble Space Telescope}$ images. In particular, we focus on the distribution of mass in Abell 2146-A in order to determine the centroid of the dark matter halo. We use object colours and morphologies to identify multiple-image systems; very conservatively, four of these systems are used as constraints on a lens mass model. We find that the centroid of the dark matter halo, constrained using the strongly lensed features, is coincident with the BCG, with an offset of ≈2 kpc between the centres of the dark matter halo and the BCG. Thus from the strong-lensing model, the X-ray cool core also leads the centroid of the dark matter in Abell 2146-A, with an offset of ≈30 kpc.JEC acknowledges support from The University of Texas at Dallas, and NASA through a Fellowship of the Texas Space Grant Consortium. Based on observations made with the NASA/ESA HST, obtained through programme 12871 through the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. Additional funding supporting JEC, LJK, and DIC came from a grant from the Space Telescope Science Institute under the same programme 12871. Additional funding supporting JEC and LJK came from a grant from the National Science Foundation, number 1517954. This work was supported in part by World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan, and JSPS KAKENHI Grant Number 26800093 and 15H05892

Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5–15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%). CRLF2-r co-occurred with primary chromosomal rearrangements but the majority (111/161, 69%) had B-other ALL. Copy number alteration (CNA) profiles were similar to B-other ALL, although CRLF2-r patients harbored higher frequencies of IKZF1 (60/138, 43% vs. 77/1351, 24%) and BTG1 deletions (20/138, 15% vs. 3/1351, 1%). There were significant differences in CNA profiles between IGH-CRLF2 and P2RY8-CRLF2 patients: IKZF1 (25/35, 71% vs. 36/108, 33%, P < .001), BTG1 (11/35, 31% vs. 10/108, 9%, P =.004), and ADD3 deletions (9/19, 47% vs. 5/38, 13%, P =.008). A novel gene fusion, USP9X-DDX3X, was discovered in 10/54 (19%) of patients. Pathway analysis of the mutational profile revealed novel involvement for focal adhesion. Although the functional relevance of many of these abnormalities are unknown, they likely activate additional pathways, which may represent novel therapeutic targets

Using knowledge brokers to facilitate the uptake of pediatric measurement tools into clinical practice: a before-after intervention study

<p>Abstract</p> <p>Background</p> <p>The use of measurement tools is an essential part of good evidence-based practice; however, physiotherapists (PTs) are not always confident when selecting, administering, and interpreting these tools. The purpose of this study was to evaluate the impact of a multifaceted knowledge translation intervention, using PTs as knowledge brokers (KBs) to facilitate the use in clinical practice of four evidence-based measurement tools designed to evaluate and understand motor function in children with cerebral palsy (CP). The KB model evaluated in this study was designed to overcome many of the barriers to research transfer identified in the literature.</p> <p>Methods</p> <p>A mixed methods before-after study design was used to evaluate the impact of a six-month KB intervention by 25 KBs on 122 practicing PTs' self-reported knowledge and use of the measurement tools in 28 children's rehabilitation organizations in two regions of Canada. The model was that of PT KBs situated in clinical sites supported by a network of KBs and the research team through a broker to the KBs. Modest financial remuneration to the organizations for the KB time (two hours/week for six months), ongoing resource materials, and personal and intranet support was provided to the KBs. Survey data were collected by questionnaire prior to, immediately following the intervention (six months), and at 12 and 18 months. A mixed effects multinomial logistic regression was used to examine the impact of the intervention over time and by region. The impact of organizational factors was also explored.</p> <p>Results</p> <p>PTs' self-reported knowledge of all four measurement tools increased significantly over the six-month intervention, and reported use of three of the four measurement tools also increased. Changes were sustained 12 months later. Organizational culture for research and supervisor expectations were significantly associated with uptake of only one of the four measurement tools.</p> <p>Conclusions</p> <p>KBs positively influenced PTs' self-reported knowledge and self-reported use of the targeted measurement tools. Further research is warranted to investigate whether this is a feasible, cost-effective model that could be used more broadly in a rehabilitation setting to facilitate the uptake of other measurement tools or evidence-based intervention approaches.</p

Moody Music Generator: Characterising Control Parameters Using Crowdsourcing.

Abstract. We characterise the expressive effects of a music generator capable of varying its moods through two control parameters. The two control parameters were constructed on the basis of existing work on va-lence and arousal in music, and intended to provide control over those two mood factors. In this paper we conduct a listener study to determine how people actually perceive the various moods the generator can produce. Rather than directly attempting to validate that our two control param-eters represent arousal and valence, instead we conduct an open-ended study to crowd-source labels characterising different parts of this two-dimensional control space. Our aim is to characterise perception of the generator’s expressive space, without constraining listeners ’ responses to labels specifically aimed at validating the original arousal/valence moti-vation. Subjects were asked to listen to clips of generated music over the Internet, and to describe the moods with free-text labels. We find that the arousal parameter does roughly map to perceived arousal, but that the nominal “valence ” parameter has strong interaction with the arousal parameter, and produces different effects in different parts of the con-trol space. We believe that the characterisation methodology described here is general and could be used to map the expressive range of other parameterisable generators.