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Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.
Intensive longitudinal data (ILD) collected in mobile health (mHealth) studies contain rich information on the dynamics of multiple outcomes measured frequently over time. Motivated by an mHealth study in which participants self-report the intensity of many emotions multiple times per day, we describe a dynamic factor model that summarizes ILD as a low-dimensional, interpretable latent process. This model consists of (i) a measurement submodel—a factor model—that summarizes the multivariate longitudinal outcome as lower-dimensional latent variables and (ii) a structural submodel—an Ornstein–Uhlenbeck (OU) stochastic process—that captures the dynamics of the multivariate latent process in continuous time. We derive a closed-form likelihood for the marginal distribution of the outcome and the computationally-simpler sparse precision matrix for the OU process. We propose a block coordinate descent algorithm for estimation and use simulation studies to show that it has good statistical properties with ILD. Then, we use our method to analyze data from the mHealth study. We summarize the dynamics of 18 emotions using models with one, two, and three time-varying latent factors, which correspond to different behavioral science theories of emotions. We demonstrate how results can be interpreted to help improve behavioral science theories of momentary emotions, latent psychological states, and their dynamics.
The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
Inspired by laboratory experiments showing internal waves generated by a plume impinging upon a stratified fluid layer (Ansong & Sutherland. 2010 J. Fluid Mech.648, 405–434), we perform large eddy simulations in three dimensions to examine the structure and source of internal waves emanating from the top of a plume that rises vertically into stratification whose strength ranges over two orders of magnitude between different simulations. Provided the plume is sufficiently energetic to penetrate into the stratified layer, internal waves are generated with frequencies in a relatively narrow band moderately smaller than the buoyancy frequency. Through adaptations of ray theory including viscosity and use of dynamic mode decomposition, we show that the waves originate from within the turbulent flow rather than at the turbulent/non-turbulent interface between the fountain top and the surrounding stratified fluid.
North Carolina growers have long struggled to control Italian ryegrass, and recent research has confirmed that some Italian ryegrass biotypes have become resistant to nicosulfuron, glyphosate, clethodim, and paraquat. Integrating alternative management strategies is crucial to effectively control such biotypes. The objectives of this study were to evaluate Italian ryegrass control with cover crops and fall-applied residual herbicides and investigate cover crop injury from residual herbicides. This study was conducted during the fall/winter of 2021–22 in Salisbury, NC, and fall/winter of 2021–22 and 2022–23 in Clayton, NC. The study was designed as a 3 × 5 split-plot in which the main plot consisted of three cover crop treatments (no-cover, cereal rye at 80 kg ha−1, and crimson clover at 18 kg ha−1), and the subplots consisted of five residual herbicide treatments (S-metolachlor, flumioxazin, metribuzin, pyroxasulfone, and nontreated). In the 2021–22 season at Clayton, metribuzin injured cereal rye and crimson clover 65% and 55%, respectively. However, metribuzin injured both cover crops ≤6% in 2022–23. Flumioxazin resulted in unacceptable crimson clover injury of 50% and 38% in 2021–22 and 2022–23 in Clayton and 40% in Salisbury, respectively. Without preemergence herbicides, cereal rye controlled Italian ryegrass by 85% and 61% at 24 wk after planting in 2021–22 and 2022–23 in Clayton and 82% in Salisbury, respectively. In 2021–22, Italian ryegrass seed production was lowest in cereal rye plots at both locations, except when it was treated with metribuzin. For example, in Salisbury, cereal rye plus metribuzin resulted in 39,324 seeds m–2, compared to ≤4,386 seeds m–2 from all other cereal rye treatments. In 2022–23, Italian ryegrass seed production in cereal rye was lower when either metribuzin or pyroxasulfone were used preemergence (2,670 and 1,299 seeds m–2, respectively) compared with cereal rye that did not receive an herbicide treatment (5,600 seeds m–2). cereal rye (Secale cereale L.) and crimson clover (Trifolium incarnatum L.)
Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.
An experiment was conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to evaluate residual herbicide-coated fertilizer for cotton tolerance and Palmer amaranth control. Treatments included acetochlor, atrazine, dimethenamid-P, diuron, flumioxazin, fluometuron, fluridone, fomesafen, linuron, metribuzin, pendimethalin, pyroxasulfone, pyroxasulfone + carfentrazone, S-metolachlor, and sulfentrazone. Each herbicide was individually coated on granular ammonium sulfate (AMS) and top-dressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf cotton. The check plots received the equivalent rate of nonherbicide-treated AMS. Before top-dress, all plots (including the check) were treated with glyphosate and glufosinate to control previously emerged weeds. All herbicides except metribuzin resulted in transient cotton injury. Cotton response to metribuzin varied by year and location. In 2022, metribuzin caused 11% to 39% and 8% to 17% injury at the Clayton and Rocky Mount locations, respectively. In 2023, metribuzin caused 13% to 32% injury at Clayton and 73% to 84% injury at Rocky Mount. Pyroxasulfone (91%), pyroxasulfone + carfentrazone (89%), fomesafen (87%), fluridone (86%), flumioxazin (86%), and atrazine (85%) controlled Palmer amaranth ≥85%. Pendimethalin and fluometuron were the least effective treatments, resulting in 58% and 62% control, respectively. As anticipated, early season metribuzin injury translated into yield loss; plots treated with metribuzin yielded 640 kg ha−1 and were comparable to yields after linuron (790 kg ha−1) was used. These findings suggest that with the exception of metribuzin, residual herbicides coated onto AMS may be suitable and effective in cotton production, providing growers with additional modes of action for late-season control of multiple herbicide–resistant Palmer amaranth.
We use large-eddy simulations to study the penetration of a buoyant plume carrying a passive tracer into a stably stratified layer with constant buoyancy frequency. Using a buoyancy-tracer volume distribution, we develop a method for objectively partitioning plume fluid in buoyancy-tracer space into three regions, each of which corresponds to a coherent region in physical space. Specifically, we identify a source region where undiluted plume fluid enters the stratified layer, a transport region where much of the transition from undiluted to mixed fluid occurs in the plume cap and an accumulation region corresponding to a radially spreading intrusion. This method enables quantification of different measures of turbulence and mixing within each of the three regions, including potential energy and turbulent kinetic energy dissipation rates, an activity parameter and the instantaneous mixing efficiency. We find that the most intense buoyancy gradients lie in a thin layer at the cap of the penetrating plume. This provides the primary stage of mixing between plume and environment and exhibits a mixing efficiency around 50 %. Newly generated mixtures of environmental and plume fluid join the intrusion and experience relatively weak turbulence and buoyancy gradients. As the intrusion spreads radially, environmental fluid surrounding the intrusion is mixed into the intrusion with moderate mixing efficiency. This dominates the volume of environmental fluid entrained into the region containing plume fluid. However, the ‘strongest’ entrainment, as measured by the specific entrainment rate, is largest in the plume cap, where the most buoyant environmental fluid is entrained.
Sample materials such as sediments and soils contain complex mixtures of different carbon-containing compounds. These bulk samples can be split into individual fractions, based on the temperature of thermal decomposition of their components. When coupled with radiocarbon (14C) measurement of the isolated fractions, this approach offers the advantage of directly investigating the residence time, turnover time, source, or age of the different components within a mixed sample, providing important insights to better understand the cycling of carbon in the environment. Several laboratories have previously reported different approaches to separate radiocarbon samples based on temperature in what is a growing area of interest within the research community. Here, we report the design and operation of a new ramped oxidation facility for separation of sample carbon on the basis of thermal resistance at the NEIF Radiocarbon Laboratory in East Kilbride, UK. Our new instrumentation shares some characteristics with the previously-reported systems applying ramped oxidation and/or ramped pyrolysis for radiocarbon measurement, but also has several differences which we describe and discuss. We also present the results of a thorough program of testing of the new system, which demonstrates both the reproducibility of the thermograms generated during sample combustion, and the reliability of the radiocarbon measurements obtained on individual sample fractions. This is achieved through quantification of the radiocarbon background and analysis of multiple standards of known 14C content during standard operation of the instrumentation.
Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.
The mechanics underlying ice–skate friction remain uncertain despite over a century of study. In the 1930s, the theory of self-lubrication from frictional heat supplanted an earlier hypothesis that pressure melting governed skate friction. More recently, researchers have suggested that a layer of abraded wear particles or the presence of quasi-liquid molecular layers on the surface of ice could account for its slipperiness. Here, we assess the dominant hypotheses proposed to govern ice–skate friction and describe experiments conducted in an indoor skating rink aimed to provide observations to test these hypotheses. Our results indicate that the brittle failure of ice under rapid compression plays a strong role. Our observations did not confirm the presence of full-contact water films and are more consistent with the presence of lubricating ice-rich slurries at discontinuous high-pressure zones (HPZs). The presence of ice-rich slurries supporting skates through HPZs merges pressure-melting, abrasion and lubricating films as a unified hypothesis for why skates are so slippery across broad ranges of speeds, temperatures and normal loads. We suggest tribometer experiments to overcome the difficulties of investigating these processes during actual skating trials.
We present an overview of the Middle Ages Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey, a Large Program on the European Southern Observatory Very Large Telescope. MAGPI is designed to study the physical drivers of galaxy transformation at a lookback time of 3–4 Gyr, during which the dynamical, morphological, and chemical properties of galaxies are predicted to evolve significantly. The survey uses new medium-deep adaptive optics aided Multi-Unit Spectroscopic Explorer (MUSE) observations of fields selected from the Galaxy and Mass Assembly (GAMA) survey, providing a wealth of publicly available ancillary multi-wavelength data. With these data, MAGPI will map the kinematic and chemical properties of stars and ionised gas for a sample of 60 massive (${>}7 \times 10^{10} {\mathrm{M}}_\odot$) central galaxies at $0.25 < z <0.35$ in a representative range of environments (isolated, groups and clusters). The spatial resolution delivered by MUSE with Ground Layer Adaptive Optics ($0.6-0.8$ arcsec FWHM) will facilitate a direct comparison with Integral Field Spectroscopy surveys of the nearby Universe, such as SAMI and MaNGA, and at higher redshifts using adaptive optics, for example, SINS. In addition to the primary (central) galaxy sample, MAGPI will deliver resolved and unresolved spectra for as many as 150 satellite galaxies at $0.25 < z <0.35$, as well as hundreds of emission-line sources at $z < 6$. This paper outlines the science goals, survey design, and observing strategy of MAGPI. We also present a first look at the MAGPI data, and the theoretical framework to which MAGPI data will be compared using the current generation of cosmological hydrodynamical simulations including EAGLE, Magneticum, HORIZON-AGN, and Illustris-TNG. Our results show that cosmological hydrodynamical simulations make discrepant predictions in the spatially resolved properties of galaxies at $z\approx 0.3$. MAGPI observations will place new constraints and allow for tangible improvements in galaxy formation theory.
Individuals with treatment-resistant depression (TRD) experience a high burden of illness. Current guidelines recommend a stepped care approach for treating depression, but the extent to which best-practice care pathways are adhered to is unclear.
Aims
To explore the extent and nature of ‘treatment gaps’ (non-adherence to stepped care pathways) experienced by a sample of patients with established TRD (non-response to two or more adequate treatments in the current depressive episode) across three cities in the UK.
Method
Five treatment gaps were considered and compared with guidelines, in a cross-sectional retrospective analysis: delay to receiving treatment, lack of access to psychological therapies, delays to medication changes, delays to adjunctive (pharmacological augmentation) treatment and lack of access to secondary care. We additionally explored participant characteristics associated with the extent of treatment gaps experienced.
Results
Of 178 patients with TRD, 47% had been in the current depressive episode for >1 year before initiating antidepressants; 53% had received adequate psychological therapy. A total of 47 and 51% had remained on an unsuccessful first and second antidepressant trial respectively for >16 weeks, and 24 and 27% for >1 year before medication switch, respectively. Further, 54% had tried three or more antidepressant medications within their episode, and only 11% had received adjunctive treatment.
Conclusions
There appears to be a considerable difference between treatment guidelines for depression and the reality of care received by people with TRD. Future research examining representative samples of patients could determine recommendations for optimising care pathways, and ultimately outcomes, for individuals with this illness.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.
Methods.
The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.
Results.
We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.
Conclusions.
We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
The volume of evidence from scientific research and wider observation is greater than ever before, but much is inconsistent and scattered in fragments over increasingly diverse sources, making it hard for decision-makers to find, access and interpret all the relevant information on a particular topic, resolve seemingly contradictory results or simply identify where there is a lack of evidence. Evidence synthesis is the process of searching for and summarising a body of research on a specific topic in order to inform decisions, but is often poorly conducted and susceptible to bias. In response to these problems, more rigorous methodologies have been developed and subsequently made available to the conservation and environmental management community by the Collaboration for Environmental Evidence. We explain when and why these methods are appropriate, and how evidence can be synthesised, shared, used as a public good and benefit wider society. We discuss new developments with potential to address barriers to evidence synthesis and communication and how these practices might be mainstreamed in the process of decision-making in conservation.
Cognitive Behaviour Therapy (CBT) is an effective psychological intervention for children and young people with anxiety disorders (James et al, 2013). This has led to interest in whether CBT programmes can be widely provided in schools to prevent or ameliorate anxiety symptoms in children.
Objective
Results from school based anxiety prevention trials are encouraging (Neil & Christensen 2009; Fisak, Richard, Mann 2011). Before the widespread use of school based preventive programmes can be advocated methodologically robust evaluations are required to demonstrate that they are effective when transported to everyday settings.
Aim
To undertake a pragmatic randomised controlled trial (RCT) of a universal school based CBT programme (Friends for Life) for children aged 9-10 years of age .
Methods
Three arm RCT comparing Friends for Life delivered by trained health or school leaders with usual school provision (Stallard et al,2012). Primary outcome the Revised Child Anxiety and Depression Scale (RCADS) at 12 month follow-up.
Results
A total of 1362 children from 40 schools participated with 1257 (92%) being re-assessed at follow-up. There was a difference in adjusted mean child report RCADS scores for health-led versus school-led FRIENDS (−3.94, 95%CI −6.41 to −1.47) and health-led FRIENDS versus usual school provision (2.66, 95%CI −5.22 to −0.09). Health-led CBT resulted in greater reductions in symptoms of anxiety than the other two arms (Stallard et al 2014),
Conclusion
Our pragmatic trial demonstrates that universally delivered anxiety prevention programmes can be effective when transported into schools. However, effectiveness varies depending upon who delivers them.
The symptoms of bipolar disorder are sometimes misrecognised for unipolar depression and inappropriately treated with antidepressants. This may be associated with increased risk of developing mania. However, the extent to which this depends on what type of antidepressant is prescribed remains unclear.
Aims
To investigate the association between different classes of antidepressants and subsequent onset of mania/bipolar disorder in a real-world clinical setting.
Methods
Data on prior antidepressant therapy were extracted from 21,012 adults with unipolar depression receiving care from the South London and Maudsley NHS Foundation Trust (SLaM). multivariable Cox regression analysis (with age and gender as covariates) was used to investigate the association of antidepressant therapy with risk of developing mania/bipolar disorder.
Results
In total, 91,110 person-years of follow-up data were analysed (mean follow-up: 4.3 years). The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). The most frequently prescribed antidepressants were SSRIs (35.5%), mirtazapine (9.4%), venlafaxine (5.6%) and TCAs (4.7%). Prior antidepressant treatment was associated with an increased incidence of mania/bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with SSRIs (hazard ratio 1.34, 95% CI 1.18–1.52) and venlafaxine (1.35, 1.07–1.70).
Conclusions
In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Mood instability is an important problem but has received relatively little research attention. Natural language processing (NLP) is a novel method, which can used to automatically extract clinical data from electronic health records (EHRs).
Aims
To extract mood instability data from EHRs and investigate its impact on people with mental health disorders.
Methods
Data on mood instability were extracted using NLP from 27,704 adults receiving care from the South London and Maudsley NHS Foundation Trust (SLaM) for affective, personality or psychotic disorders. These data were used to investigate the association of mood instability with different mental disorders and with hospitalisation and treatment outcomes.
Results
Mood instability was documented in 12.1% of people included in the study. It was most frequently documented in people with bipolar disorder (22.6%), but was also common in personality disorder (17.8%) and schizophrenia (15.5%). It was associated with a greater number of days spent in hospital (B coefficient 18.5, 95% CI 12.1–24.8), greater frequency of hospitalisation (incidence rate ratio 1.95, 1.75–2.17), and an increased likelihood of prescription of antipsychotics (2.03, 1.75–2.35).
Conclusions
Using NLP, it was possible to identify mood instability in a large number of people, which would otherwise not have been possible by manually reading clinical records. Mood instability occurs in a wide range of mental disorders. It is generally associated with poor clinical outcomes. These findings suggest that clinicians should screen for mood instability across all common mental health disorders. The data also highlight the utility of NLP for clinical research.
Disclosure of interest
The authors have not supplied their declaration of competing interest.