Measurement of compulsive exercise is important for the study of eating pathology in individuals who regularly participate in sport and exercise. The current study examined the factor structure, ...internal consistency and validity of the compulsive exercise test (CET) in regular exercisers. Participants were recruited via the internet and from sport clubs (n = 313 adults; M = 32 years; 57% female). A three-factor model for the CET was supported which included the weight control exercise, avoidance and rule-driven behaviour, and mood improvement subscales (fit statistics for the three-factor model: χ
2
SB
=
4.39; CFI = .95; NNFI = .94, RMSEA = .100, 95% CI: .093-.110, AIC = 656.92). The subscales lack of exercise enjoyment and exercise rigidity were not retained. All factors demonstrated acceptable internal consistency with Cronbach's α = .77 to .91. The weight control exercise and avoidance and rule-driven behaviour subscales were significantly related to eating disorder symptoms. Given the association between CET subscales and eating disorder symptoms, the CET three-factor model may be informative when assessing eating pathology in individuals who regularly exercise.
Optimal energy goals for adult, obese critically ill surgical patients are unclear. To date, there has been little data comparing feeding regimens for obese and non-obese critically ill surgical ...patients and the effect on outcomes. The objective was to compare the effect of hypoenergetic and euenergetic feeding goals in critically ill obese patients on outcomes, including infection, intensive care unit length of stay, and mortality. We hypothesized that hypoenergetic feeding of patients with premorbid obesity (body mass index ≥ 30 kg•m−2) during critical illness does not affect clinical outcomes. Post hoc analyses were performed on critically ill surgical patients enrolled in a randomized controlled trial. Patients were randomized to receive 25-30 kcal•kg−1•d−1 (105-126 kJ.kg−1•d−1, euenergetic) or 12.5-15 kcal•kg−1•d−1 (52-63 kJ.kg−1 •d−1, hypoenergetic), with equal protein allocation (1.5 g•kg−1•d−1). The effect of feeding regimen on outcomes in obese and nonobese patients were assessed. Of the 83 patients, 30 (36.1%) were obese (body mass index ≥ 30 kg•m−2). Average energy intake differed based on feeding regimen (hypoenergetic: 982±61 vs euenergetic: 1338±92 kcal•d−1, P = .02). Comparing obese and nonobese patients, there was no difference in the percentage acquiring an infection (66.7% 20/30 vs 77.4% 41/53, P = .29), intensive care unit length of stay (16.4±3.7 vs 14.3±0.9 days, P = .39), or mortality (10% 3/30 vs 7.6% 4/53, P = .7). Within the subset of obese patients, the percentage acquiring an infection (hypoenergetic: 78.9% 15/19 vs euenergetic: 45.5% 5/11, P = .11) was not affected by the feeding regimen. Within the subset of nonobese patients, there was a trend toward more infections in the euenergetic group (hypoenergetic: 63.6% 14/22 vs euenergetic: 87.1% 27/31, P = .05). Hypoenergetic feeding does not appear to affect clinical outcomes positively or negatively in critically ill patients with premorbid obesity.
As per the 2017 WHO fact sheet, Coronary Artery Disease (CAD) is the primary cause of death in the world, and accounts for 31% of total fatalities. The unprecedented 17.6 million deaths caused by CAD ...in 2016 underscores the urgent need to facilitate proactive and accelerated pre-emptive diagnosis. The innovative and emerging Machine Learning (ML) techniques can be leveraged to facilitate early detection of CAD which is a crucial factor in saving lives. The standard techniques like angiography, that provide reliable evidence are invasive and typically expensive and risky. In contrast, ML model generated diagnosis is non-invasive, fast, accurate and affordable. Therefore, ML algorithms can be used as a supplement or precursor to the conventional methods. This research demonstrates the implementation and comparative analysis of K Nearest Neighbor (k-NN) and Random Forest ML algorithms to achieve a targeted "At Risk" CAD classification using an emerging set of 35 cytokine biomarkers that are strongly indicative predictive variables that can be potential targets for therapy. To ensure better generalizability, mechanisms such as data balancing, repeated k-fold cross validation for hyperparameter tuning, were integrated within the models. To determine the separability efficacy of "At Risk" CAD versus Control achieved by the models, Area under Receiver Operating Characteristic (AUROC) metric is used which discriminates the classes by exhibiting tradeoff between the false positive and true positive rates.
A total of 2 classifiers were developed, both built using 35 cytokine predictive features. The best AUROC score of .99 with a 95% Confidence Interval (CI) (.982,.999) was achieved by the Random Forest classifier using 35 cytokine biomarkers. The second-best AUROC score of .954 with a 95% Confidence Interval (.929,.979) was achieved by the k-NN model using 35 cytokines. A p-value of less than 7.481e-10 obtained by an independent t-test validated that Random Forest classifier was significantly better than the k-NN classifier with regards to the AUROC score. Presently, as large-scale efforts are gaining momentum to enable early, fast, reliable, affordable, and accessible detection of individuals at risk for CAD, the application of powerful ML algorithms can be leveraged as a supplement to conventional methods such as angiography. Early detection can be further improved by incorporating 65 novel and sensitive cytokine biomarkers. Investigation of the emerging role of cytokines in CAD can materially enhance the detection of risk and the discovery of mechanisms of disease that can lead to new therapeutic modalities.
BackgroundAdvanced lung cancer kills 90% of patients within a decade, underscoring an urgent need for improved early detection and prevention technologies. T cell responses are initiated and ...dysregulated during early carcinogenesis in vivo, providing a potential basis for immune-focused early cancer detection and interception. Here we examined cross-tissue T cell dynamics during human and murine lung squamous carcinogenesis to assess their utility in lung cancer early detection and immune-interception.MethodsOver a decade ago we initiated a clinical autofluorescence bronchoscopy surveillance program at University College London, to longitudinally monitor preinvasie pulmonary neoplasia in respiratory patients with a smoking history. We deeply profiled the immune and genomic landscape in rarely analysed, laser-captured, preinvasive bronchial biopsies and paired PBMCs from over 100 patients using either spectral cytometry, scRNAseq, TCRseq and/or WES. In parallel, we generated and immune-profiled an N-nitroso-tris-chloroethylurea (NTCU)-induced mouse model that replicated the histopathology and immune landscape of progressive human central airway neoplasia.ResultsOur scRNAseq data demonstrate an extensive remodelling of MHCII signalling networks during lung squamous (LUSC) carcinogenesis; patterned by loss of MHCII on basal airway epithelium, gain on B-cells and cDC2s and concomitant expansion of highly suppressive Basic Leucine Zipper ATF-Like Transcription Factor-expressing (BATF+) Treg cells (BATF+Tregs). BATF+Treg signatures significantly increased during LUSC carcinogenesis in independent bulk RNAseq from over 100 biopsies and defined immunotherapy failure and truncated survival in stage I LUSC. We recapitulated these data in the NTCU mouse model, wherein BATF+ Tregs gradually accumulated in preinvasive and invasive lesions and could be intercepted via PI3Kδ inhibition, which prevented lung tumours in 50% of mice.BATF+Tregs in the tissue shared TCRs with activated Tregs in the blood during early-stage lung cancer, prompting us to profile PBMCs from 107 patients via high-dimensional cytometry and deep TCRseq. Activated Treg frequencies and global TCR metrics were comparable between healthy individuals and those with low grade pulmonary neoplasia. However, we observed a dramatic increase in circulating activated Tregs and cancer-associated or total clonal TCR expansion in patients with high grade neoplasia (50% average risk of LUSC development) and stage Ia lung cancer. Preliminary multivariate regression models showed that liquid immune metrics outperformed clinical variables in classification of high vs low grade neoplasia and forecasted significantly increased risk of future LUSC diagnosis.ConclusionsThese data provide a roadmap for harnessing CD4 T cell differentiation as a basis for the early detection and precision immune-interception of lung cancer.Ethics ApprovalAll studies used are ethically approved, the PI is Professor Sam Janes.Reference numbers for approval are1. REC 01/0148, REC 20/SC/0128, REC 18/SC/051,All participants gave informed consent.
Infant and early childhood mental health consultation (IECMHC) is a national model with proven positive outcomes for children, teachers and classrooms, as well as effectively addressing racial ...inequity in preschool suspension and expulsion rates. This paper discusses recent efforts in the Maryland IECMHC program to deeply and systematically address equity and increase consultant capacity to understand and address racial inequity within early childhood settings.
Background
Regional lymph node metastasis (RLNM) occurs infrequently in patients with soft tissue sarcoma (STS), although certain STS subtypes have a higher propensity for RLNM. The identification of ...RLNM has significant implications for staging and prognosis; however, the precise impact of node-positive disease on patient survival remains a topic of controversy. Although the benefits of sentinel lymph node biopsy (SLNB) are well documented in patients with melanoma and breast cancer, whether this procedure offers a benefit in STS is controversial.
Methods
A systematic literature search was performed and articles reviewed to determine if SLNB in patients with extremity/truncal STS impacts disease-free or overall survival.
Results
Six studies were included. Rates of sentinel lymph node positivity were heterogeneous (range 4.3–50%). The impact of SLNB on patient outcomes remains unclear. The overall quality of available evidence was low, as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system.
Conclusions
The literature addressing the impact of nodal basin evaluation on the staging and management of patients with extremity/truncal STS is confounded by heterogeneous patient cohorts and clinical practices. Multicenter prospective studies are warranted to determine the true incidence of RLNM and whether SLNB could benefit patients with clinically occult RLNM at diagnosis.
Autistic adolescents who experience anxiety face unique challenges. Cognitive-behavioural therapy is an evidence-based treatment for anxiety in Autistic children, yet there is less evidence for ...adaptations of these CBT group interventions for adolescent populations.
This study evaluated the efficacy of the Cool Kids Autism Spectrum Disorder Anxiety program in reducing anxiety in Autistic adolescents. Forty-nine Autistic adolescents with clinically significant anxiety (ages 12–18; IQ > 70) were randomly assigned to the intervention condition or waitlist.
There were reductions in anxiety severity for the intervention group compared to waitlist, in diagnostic status, clinical severity, and parent ratings. Post-treatment, 72% of participants in the intervention group showed remission of their primary anxiety disorder diagnosis compared to 31.6% of the waitlist.
The Cool Kids ASD Anxiety Program may be effective for reducing clinical anxiety in Autistic adolescents, and future studies should replicate these findings with additional consideration of the role of parents in treatment outcomes.
•This trial evaluated a group-based cognitive-behavioural therapy program compared to waitlist control.•After treatment, 72% of people no longer had anxiety disorders, compared to only 30% of people on the waitlist.•There were also improvements in other symptoms of mental ill-health, and these benefits persisted 6 months after treatment.
Parental preconception exposures to built and natural outdoor environments could influence pregnancy and birth outcomes either directly, or via a range of health-related behaviours and conditions. ...However, there is no existing review summarising the evidence linking natural and built characteristics, such as air and noise pollution, walkability, greenness with pregnancy and birth outcomes. Therefore, the planned scoping review aims to collate and map the published literature on parental preconception exposures to built and natural outdoor environments and adverse pregnancy and birth outcomes. We will search electronic databases (MEDLINE, EMBASE, Scopus) to identify studies for inclusion. Studies will be included if they empirically assess the relationship between maternal and paternal preconception exposures to physical natural and built environment features that occur outdoors in the residential neighbourhood and adverse pregnancy and birth outcomes. Two reviewers will independently screen titles and abstracts, and then the full text. Data extraction and assessment of study quality will be performed by one researcher and checked by a second researcher. Results will be summarised in a narrative synthesis, with additional summaries presented as tables and figures. The scoping review will be disseminated via a peer-reviewed publication, at academic conferences, and published on a website.
Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report ...SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean SD anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL 6.2 vs 4555.3 U/mL 5.4, p <0.0001; 26.8 days 95% CI 26.2 - 27.5 vs 47.6 days 45.5 - 49.8, p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL 5.0 vs 784.0 U/mL 3.5, p <0.0001; 35.9 days 34.9 - 36.8 vs 58.0 days 55.0 - 61.3, p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.
Abstract
Background
Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized ...prevalences of prolonged symptoms 3 months post–SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron).
Methods
This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system–based symptoms, and ≥3 symptoms across variants among participants with a positive (“COVID-positive”) or negative SARS-CoV-2 test (“COVID-negative”) at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status.
Results
The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants.
Conclusions
Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms.
Clinical Trials Registration. NCT04610515.
This prospective study including 2402 SARS-CoV-2–positive participants noted more severe fatigue and ≥3 symptoms at 3 months after acute illness in the pre-Delta cohort compared with Delta and Omicron. However, this was no longer significant after accounting for vaccination status.
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