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On the persistence of discourse predictions:The facilitative effect of discourse markers diminishes in the presence of intervening material
No full textThe current study investigates for how long readers maintain expectations about an upcoming discourse relation. We use the pair of discourse markers On the one hand (OT1H) and On the other hand (OTOH) to test the facilitative effect of OT1H on the processing of OTOH and the sensitivity of this effect to the presence of intervening material. Results from a story continuation study indicate that intervening material slightly weakens the effect of OT1H on offline representations of the discourse. Results from a self-paced reading and two eye-tracking studies suggest that the presence of intervening material diminishes the facilitative effect of OT1H in online processing. These results support memory-based models of processing by showing that discourse dependencies, while they are built as fine-grained representations, are not unbounded in real-time processing
The evolution of serious health-related suffering from 1990 to 2021:an update to The Lancet Commission on global access to palliative care and pain relief
No full textBACKGROUND: The Lancet Commission on global access to palliative care and pain relief introduced the concept of serious health-related suffering (SHS) to measure the worldwide dearth of palliative care. This Article provides an extended analysis of SHS from 1990 to 2021 and the corresponding global palliative care need.METHODS: This Article is the first to apply the SHS 2·0 method published in 2024, incorporating prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study to improve non-decedent estimates that account for country-level epidemiological variation; adjusting for non-decedent double counting of HIV/AIDS, cancer, cerebrovascular disease, and dementia; improving the non-decedent estimates for cancer using survivorship data from the Global Cancer Observatory and for HIV/AIDS incorporating access to antiretroviral therapy; differentiating by sex; considering more specific age groups allowing for better estimates, especially in children; and adding endocrine, metabolic, blood, and immune disorders to the health conditions causing SHS. We describe SHS trends globally and within country income groups, differentiating among decedents and non-decedents, by health conditions, sex, and across child and adult age groups.FINDINGS: The SHS global burden increased by 74% between 1990 and 2021 to almost 73·5 million individuals, with population growth accounting for only half of that increase. Low-income and middle-income countries (LMICs) accounted for 80% of SHS, with an increase of 83% from 1990 to 2021 compared with a 46% increase in high-income countries (HICs). Between 1990 and 2021, the decedent burden increased by 35%, whereas SHS in non-decedents more than doubled, accounting for 63% of SHS by 2021. The proportion of SHS from communicable diseases declined, especially in LMICs; however, the absolute number stayed relatively stable and even increased from 2019 to 2021 with the start of the COVID-19 pandemic. SHS from non-communicable diseases drastically increased, led by cancer (excluding leukaemia), cardiovascular diseases, and dementia in HICs. HIV/AIDS continued to be a major contributor, accounting for a substantial share of SHS in sub-Saharan Africa. The share of SHS in children decreased from 25% of SHS in 1990 to 14% in 2021 and accounted for 33% of SHS in low-income countries, compared with 2% in HICs. In 2021, SHS in low-income countries was concentrated in female individuals aged 20-49 years (affecting 59% of this population); in HICs, SHS was concentrated in female individuals aged 70 years and older (affecting 54% of this population and probably related to dementia).INTERPRETATION: SHS and the associated need for palliative care is a major and persistent but not insurmountable challenge for health systems worldwide. Our findings highlight the urgency to both reduce the avoidable SHS burden through prevention and treatment, and guarantee comprehensive, universal access to palliative care as an equity and health system imperative, especially in LMICs.FUNDING: University of Miami, USA; Cancer Pain Relief Committee; Medical Research Council; GDS.</p
Separation of luminance and contrast modulation in steady-state visual evoked potentials
No full textNeurons in the retina and early visual cortex respond primarily to local luminance contrast rather than overall luminance energy. The distinction between luminance and contrast processing is revealed in its most striking form by the contrast asynchrony paradigm: two discs with bright and dark surrounds modulate in luminance. When the discs modulate at 3–6 Hz, there is a percept of antiphase flicker even though the luminance modulation of the patches is in phase. To establish the neural basis of this perceptual phenomenon, we conducted a study using steady-state visual evoked potentials (SSVEPs) aiming to identify specific contrast and luminance signals. Deconstructing contrast asynchrony into its constituent elements, we displayed eight discs modulating sinusoidally from dark to bright on one of three backgrounds (bright, midgray, dark). In the first experiment, disc modulation and background luminances spanned a narrow range (30–34 cd/m) to avoid VEP saturation (Weber contrast 15.5%) at two frequencies: 3 Hz, falling inside the contrast asynchrony temporal range, and 7.14 Hz, falling outside this range. In the second experiment, luminances and contrasts spanned a large range (0–64 cd/m) at three frequencies (3, 5, 7.14 Hz) to evaluate the degree to which VEP response non-linearities would affect observed data patterns. With lower contrast modulation at 3 Hz, SSVEP amplitudes and phases correspond to the temporal signatures of contrast — not luminance — modulation. However, at higher frequencies and/or contrasts, this orderly pattern was largely replaced by more complex patterns that no longer directly corresponded to the luminance or contrast of the stimulus
Social workers’ views and experiences of self-care practices:A qualitative interview study
No full textSelf-care is increasingly advocated as necessary for improving social workers’ wellbeing. However, it remains a contested term, with limited understanding of social workers’ views and experiences of what it constitutes in practice. This qualitative study employed semi-structured interviews with nine social workers from three local authorities in Scotland. Informed by vulnerability theory, a six-phase thematic analysis was applied to explore social workers’ views and experiences of self-care practices. Three key themes emerged: (1) understanding and conceptualizing self-care, illustrating practitioners’ perceptions of self-care as individualized, multifaceted strategies aimed at both personal wellbeing and professional efficacy, with heightened awareness since COVID-19; (2) the implementation paradox, highlighting fundamental tensions between acknowledging professional vulnerability and managing organizational demands, workload pressures, and insufficient institutional support; and (3) toward sustainable self-care practice, identifying pathways through deliberate individual practices, organizational support, educational preparation, and culturally-sensitive policies. Public health policymakers and healthcare organizations should prioritize structural reforms to enhance workforce resilience, thereby improving service quality, practitioner wellbeing, and overall public health outcomes
Capturing everyday parental feeding practices and eating behaviors of 3- to 5-year-old children with avid eating behavior:Ecological momentary assessment feasibility and acceptability study
Get PDFBackground: The wide use of smartphones offers large-scale opportunities for real-time data collection methods such as ecological momentary assessment (EMA) to assess how fluctuations in contextual and psychosocial factors influence parents’ feeding practices and feeding goals, particularly when feeding children with high food approaches.Objective: The main objectives of this study were to (1) assess parents/caregivers’ compliance with EMA procedures administered through a smartphone app and (2) estimate the criterion validity of the EMA to capture children’s eating occasions and parents’ feeding practices. Participant adherence, technological challenges, and data quality were used to provide an overview of the real-time dynamics of parental mood, feeding goals, and contextual factors during eating occasions. Methods: Parents in the United Kingdom with a child aged 3 to 5 years who exhibit avid eating behavior were invited to participate in a 10-day EMA study using a smartphone app. Of the 312 invited participants, 122 (39%) parents initiated the EMA study, of which 118 (96.7%) completed the full EMA period and the follow-up feasibility and acceptability survey. Results: Of those parents who completed the EMA study, 104 (87.4%) parents provided at least 7 “full” days of data (2 signal surveys and 1 event survey), despite 51 parents (43.2%) experiencing technical difficulties. The parents received notifications for morning surveys (69.9% response rate), 3 daily mood surveys (78.7% response rate), and an end-of-day survey (84.6% response rate) on each of the 10 days. Over the EMA period, a total of 2524 child eating/food request surveys were self-initiated by the participants on their smartphones, an average of 2.1 times per day per parent (SD 0.18; min=1.7, max=2.3). The majority of parents felt that the surveys made them more aware of their feelings (105/118, 89%) and activities (93/118, 79%). The frequency of daily food requests estimated by parents at baseline was significantly correlated with the frequency of food requests reported daily during the EMA period (r=0.483, P<.001). However, the number of daily food requests per day estimated at baseline (mean 4.5, SD 1.5) was significantly higher than the number of food requests reported per day during the EMA period (mean 3.7, SD 1.1), (t116=18.8, P<.001). Conclusions: This paper demonstrates the feasibility of employing EMA to investigate the intricate interplay between parental mood, feeding goals, contextual factors, and feeding practices with children exhibiting an avid eating behavior profile. However, the use of EMA needs to be carefully developed and tested with parents’ involvement to ensure successful data collection.</p
Acute LPS exposure enhances susceptibility to peripheral prion infection
Get PDFAfter peripheral infections, the initial accumulation of prions within secondary lymphoid tissues is essential for the transmission of disease to the brain. Macrophages are considered to sequester or destroy prions, but little was known of their impact on disease susceptibility after a peripheral infection. Inflammation in the peritoneal cavity can trigger the macrophage disappearance reaction, whereby the macrophages are temporarily contained within cellular aggregates on the mesothelium. We studied the impact of the bacterial lipopolysaccharide (LPS)-mediated macrophage disappearance reaction on susceptibility to an intraperitoneal prion infection. Intraperitoneal LPS injection significantly enhanced prion disease susceptibility approximately 100X when given 24-3 h before infection. The effects on disease susceptibility coincided with the reduced abundance of macrophages within the peritoneal cavity at the time of infection and the enhanced early accumulation of prions in the spleen. This suggests that the reduced recoverable abundance of macrophages in the peritoneal cavity following acute LPS-treatment, increased disease susceptibility by enhancing the initial propagation of the prions from site of exposure (peritoneal cavity) to the spleen from where they subsequently spread to the brain. Further studies may help identify novel macrophage-targeted treatments that can reduce susceptibility to peripherally acquired prion infections.</p
snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses
Get PDFPoor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences. MS lesion subtypes had different cellular compositions but surprisingly similar cell-type gene expression patterns both within and across patients, suggesting global changes. Most gene expression variability was instead explained by patient effects, allowing us to stratify patients and describe the different pathological processes occurring between patient subgroups. Future mapping of these brain molecular profiles with blood and/or CSF profiles from living MS patients will allow precision medicine approaches anchored in patient-specific pathological processes.</p
Incidence, severity, risk factors and outcomes of SARS-CoV-2 reinfections during the Omicron period:a systematic review and meta-analysis
Get PDFBACKGROUND: Our previous systematic review estimated the cumulative incidence of SARS-CoV-2 reinfections as 1.16% (95% CI = 1.01-1.33%) during the pre-Omicron period. The Omicron variant that emerged in November 2021 was significantly genetically distinct from the previous SARS-CoV-2 variants and thus, more transmissible and posed an increased risk of SARS-CoV-2 reinfections in the population. We, therefore, conducted a fresh systematic review and meta-analysis to estimate the SARS-CoV-2 reinfection burden during the Omicron period.METHODS: We searched CINAHL, Medline, Global Health, Embase, and WHO COVID-19 in October 2023 for studies reporting the SARS-CoV-2 reinfection incidence during the Omicron period. The quality of the included studies was assessed using the Joanna Briggs Institute checklists. Random effects meta-analyses were conducted to estimate the incidence, and requirement of hospitalisation of SARS-CoV-2 reinfections. Symptomatic severity of reinfections and case fatality rates were analysed narratively.RESULTS: Thirty-six studies were included. The reinfection cumulative incidence during the Omicron period was 3.35% (95% CI = 1.95-5.72%) based on data from 28 studies. The cumulative incidence was higher in 18-59-year-old adults (6.62% (95% CI = 3.22-13.12%)) compared to other age groups and in health care workers (9.88% (95% CI = 5.18-18.03%)) compared to the general population (2.48% (95% CI = 1.34-4.54%)). We estimated about 1.81% (95% CI = 0.18-15.87%) of the reinfected cases required hospitalisation based on limited and highly variable data.CONCLUSIONS: There was an increased risk of reinfections during the Omicron period compared to the pre-Omicron period. The incidence was higher in 18-59-year-old adults and health care workers and generally less severe during the Omicron period. However, data were limited on disease severity and long-term outcomes.REGISTRATION: PROSPERO: CRD42023482598.</p
A model of the mechanisms underpinning unconventional aqueous humor outflow
Get PDFPURPOSE: To develop a mathematical model of the unconventional outflow pathway.METHODS: The unconventional pathway is modeled as having two key components: the uveo-vortex and the trans-scleral pathways. The uveo-vortex pathway is modeled using Starling's law and the trans-scleral flow using predominately hydrostatic forces. We include transcytosis from the choriocapillaris (CC) and collapsibility of the suprachoroidal space (SCS) as particular features. There is considerable uncertainty in a number of model parameter values, and we identify the most significant ones using sensitivity analysis.RESULTS: The model successfully generates a fluid flow from anterior to posterior in the choroidal tissue and the SCS, which also demonstrates many of the known physiological features, including the insensitivity of the unconventional flow to fluctuations in the IOP, albumin removal by the trans-scleral flow, and the CC as a net absorber of fluid from, and supplier of albumin to, the choroidal tissue. The model supports the two previously proposed mechanisms of the action of prostaglandin F2α analogues.CONCLUSIONS: We have developed a theoretical model of the unconventional aqueous outflow pathway that successfully captures its physiological features and elucidates the actions of prostaglandin F2α analogues and other drugs.</p
Development of a diagnostic checklist to identify functional cognitive disorder versus other neurocognitive disorders
Get PDFBACKGROUND: Functional cognitive disorder (FCD) poses a diagnostic challenge due to its resemblance to other neurocognitive disorders and limited biomarker accuracy. We aimed to develop a new diagnostic checklist to identify FCD versus other neurocognitive disorders.METHODS: The clinical checklist was developed through mixed methods: (1) a literature review, (2) a three-round Delphi study with 45 clinicians from 12 countries and (3) a pilot discriminative accuracy study in consecutive patients attending seven memory services across the UK. Items gathering consensus were incorporated into a pilot checklist. Item redundancy was evaluated with phi coefficients. A briefer checklist was produced by removing items with >10% missing data. Internal validity was tested using Cronbach's alpha. Optimal cut-off scores were determined using receiver operating characteristic curve analysis.RESULTS: A full 11-item checklist and a 7-item briefer checklist were produced. Overall, 239 patients (143 FCD, 96 non-FCD diagnoses) were included. The checklist scores were significantly different across subgroups (FCD and other neurocognitive disorders) (F(2, 236)=313.3, p<0.001). The area under the curve was excellent for both the full checklist (0.97, 95% CI 0.95 to 0.99) and its brief version (0.96, 95% CI 0.93 to 0.98). Optimal cut-off scores corresponded to a specificity of 97% and positive predictive value of 91% for identifying FCD. Both versions showed good internal validity (>0.80).CONCLUSIONS: This pilot study shows that a brief clinical checklist may serve as a quick complementary tool to differentiate patients with neurodegeneration from those with FCD. Prospective blind large-scale validation in diverse populations is warranted.Cite Now.</p
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