Search

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 ± 14 years) with H215O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)—compared to the rest condition—were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor–cerebellar structures, reflecting their role in mediating sequence control. [Copyright &y& Elsevier]

In core-collapse supernovae, titanium-44 (44Ti) is produced in the innermost ejecta, in the layer of material directly on top of the newly formed compact object. As such, it provides a direct probe of the supernova engine. Observations of supernova 1987A (SN1987A) have resolved the 67.87- and 78.32--kilo--electron volt emission lines from decay of 44Ti produced in the supernova explosion. These lines are narrow and redshifted with a Doppler velocity of ~700 kilometers per second, direct evidence of large-scale asymmetry in the explosion. [ABSTRACT FROM AUTHOR]

Background: Radiation Therapy Oncology Group (RTOG) 0515 is a Phase II prospective trial designed to quantify the impact of positron emission tomography (PET)/computed tomography (CT) compared with CT alone on radiation treatment plans (RTPs) and to determine the rate of elective nodal failure for PET/CT-derived volumes.Methods: Each enrolled patient underwent definitive radiation therapy for non-small-cell lung cancer (≥ 60 Gy) and had two RTP datasets generated: gross tumor volume (GTV) derived with CT alone and with PET/CT. Patients received treatment using the PET/CT-derived plan. The primary end point, the impact of PET/CT fusion on treatment plans was measured by differences of the following variables for each patient: GTV, number of involved nodes, nodal station, mean lung dose (MLD), volume of lung exceeding 20 Gy (V20), and mean esophageal dose (MED). Regional failure rate was a secondary end point. The nonparametric Wilcoxon matched-pairs signed-ranks test was used with Bonferroni adjustment for an overall significance level of 0.05.Results: RTOG 0515 accrued 52 patients, 47 of whom are evaluable. The follow-up time for all patients is 12.9 months (2.7-22.2). Tumor staging was as follows: II = 6%; IIIA = 40%; and IIIB = 54%. The GTV was statistically significantly smaller for PET/CT-derived volumes (98.7 vs. 86.2 mL; p < 0.0001). MLDs for PET/CT plans were slightly lower (19 vs. 17.8 Gy; p = 0.06). There was no significant difference in the number of involved nodes (2.1 vs. 2.4), V20 (32% vs. 30.8%), or MED (28.7 vs. 27.1 Gy). Nodal contours were altered by PET/CT for 51% of patients. One patient (2%) has developed an elective nodal failure.Conclusions: PET/CT-derived tumor volumes were smaller than those derived by CT alone. PET/CT changed nodal GTV contours in 51% of patients. The elective nodal failure rate for GTVs derived by PET/CT is quite low, supporting the RTOG standard of limiting the target volume to the primary tumor and involved nodes. [ABSTRACT FROM AUTHOR]

Around 42% of individuals with cancer experience distress. Acceptance and commitment therapy (ACT) can reduce distress, but effects are small, and mechanisms unclear. This review aimed to identify associations between ACT processes and distress in cancer. Search terms included cancer, ACT processes, self-compassion, and distress. Six online databases and grey literature were searched until March 2022. Of 6555 papers screened, 108 studies were included with 17,195 participants. Five meta-analyses of 77 studies were conducted. Random effects meta-analyses of correlations revealed higher scores on flexible processes (acceptance, present moment awareness, self-compassion) were associated with lower distress ( r pooled  = -0.24, -0.39, -0.48, respectively); whilst higher scores on inflexible processes (experiential avoidance, cognitive fusion) were associated with higher distress ( r pooled  = 0.58, 0.57, respectively). Meta-analyses displayed moderate-to-high heterogeneity with most studies assessed as low risk of bias. Meta-regressions revealed no significant moderators (stage, time since diagnosis, gender and age). This review provides a theoretically aligned evidence base for associations between ACT processes and distress in cancer, supporting elements of ACT theory and providing targeted directions for intervention development. Due to limited evidence, future research should focus on self-as-context, values and committed action and conduct mediation analysis in controlled trials of ACT processes on distress in cancer.

Background: Individuals with transfusion-dependent β-thalassemia (TDT) experience symptoms and functional impacts that reduce their health-related quality of life. However, EQ-5D-derived health utility index scores in TDT often indicate good HRQoL, suggesting the EQ-5D may not adequately capture the impact of TDT. This study explored the disease and treatment burden of TDT and examined the appropriateness of the EQ-5D-5L descriptive system (DS) in measuring HRQoL in TDT., Methods: Adults with TDT in the United Kingdom, United States, and France completed a background questionnaire and EQ-5D-5L DS, followed by 60-minute semi-structured interviews on symptoms and HRQoL impacts of TDT (concept elicitation) and appropriateness of EQ-5D-5L DS (cognitive debrief). Transcribed interviews were analyzed using thematic and content analyses. The relationship between TDT symptoms and impacts were summarized in a conceptual model. EQ-5D-5L DS was mapped to concepts identified in the qualitative data to assess its capture of HRQoL concepts. Participants' EQ-5D-5L DS scores were compared to their qualitative descriptions for each dimension to assess their concordance., Results: Thirty participants in the United States (n = 14 [46.7%]), United Kingdom. (n = 12 [40.0%]), and France (n = 4 [13.3%]) completed the study (73.3% female; mean age = 28.4 years [standard deviation (SD) = 5.1]; mean annual red blood cell transfusion [RBCT] frequency = 18.4 [SD = 7.6]). Participants reported TDT symptoms and impacts on HRQoL, all fluctuating across the RBCT cycle. EQ-5D-5L DS did not fully capture 11 of 16 (68.8%) HRQoL concepts reported. Most participants (n = 20/27 [74.1%]) reported that EQ-5D-5L DS did not capture important aspects of living with TDT, and 42.9% (n = 12/28) reported negative/neutral overall impressions of EQ-5D-5L DS. The highest degree of discordance between participants' qualitative data and EQ-5D-5L DS dimension scores was observed with mobility (42.3%) and self-care (34.6%), where the qualitative descriptions relating to these dimensions were worse than their quantitative scores., Conclusion: Current findings suggest that EQ-5D-5L DS lacks content validity and the derived health utility index score may not fully represent the burden of disease in TDT., (© 2024. The Author(s).)

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug's safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11-16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3-15.4%), neutropenia was 7.1% (95% CI, 4.6-10.4%), and anemia was 11.3% (95% CI, 8.0-15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.

Competing Interests: K.S.-F. is the owner of CellTrend producing ELISA kits for the determination of antibodies against GPCR.

Background and Aims: Chronic inflammation and autoimmunity contribute to cardiovascular (CV) disease. Recently, autoantibodies (aAbs) against the CXC-motif-chemokine receptor 3 (CXCR3), a G protein-coupled receptor with a key role in atherosclerosis, have been identified. The role of anti-CXCR3 aAbs for CV risk and disease is unclear., Methods: Anti-CXCR3 aAbs were quantified by a commercially available enzyme-linked immunosorbent assay in 5000 participants (availability: 97.1%) of the population-based Gutenberg Health Study with extensive clinical phenotyping. Regression analyses were carried out to identify determinants of anti-CXCR3 aAbs and relevance for clinical outcome (i.e. all-cause mortality, cardiac death, heart failure, and major adverse cardiac events comprising incident coronary artery disease, myocardial infarction, and cardiac death). Last, immunization with CXCR3 and passive transfer of aAbs were performed in ApoE(-/-) mice for preclinical validation., Results: The analysis sample included 4195 individuals (48% female, mean age 55.5 ± 11 years) after exclusion of individuals with autoimmune disease, immunomodulatory medication, acute infection, and history of cancer. Independent of age, sex, renal function, and traditional CV risk factors, increasing concentrations of anti-CXCR3 aAbs translated into higher intima-media thickness, left ventricular mass, and N-terminal pro-B-type natriuretic peptide. Adjusted for age and sex, anti-CXCR3 aAbs above the 75th percentile predicted all-cause death [hazard ratio (HR) (95% confidence interval) 1.25 (1.02, 1.52), P = .029], driven by excess cardiac mortality [HR 2.51 (1.21, 5.22), P = .014]. A trend towards a higher risk for major adverse cardiac events [HR 1.42 (1.0, 2.0), P = .05] along with increased risk of incident heart failure [HR per standard deviation increase of anti-CXCR3 aAbs: 1.26 (1.02, 1.56), P = .03] may contribute to this observation. Targeted proteomics revealed a molecular signature of anti-CXCR3 aAbs reflecting immune cell activation and cytokine-cytokine receptor interactions associated with an ongoing T helper cell 1 response. Finally, ApoE(-/-) mice immunized against CXCR3 displayed increased anti-CXCR3 aAbs and exhibited a higher burden of atherosclerosis compared to non-immunized controls, correlating with concentrations of anti-CXCR3 aAbs in the passive transfer model., Conclusions: In individuals free of autoimmune disease, anti-CXCR3 aAbs were abundant, related to CV end-organ damage, and predicted all-cause death as well as cardiac morbidity and mortality in conjunction with the acceleration of experimental atherosclerosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dysautonomia tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2 vaccination of healthy controls ( N = 89; 71 females; mean/median age: 39/49 years) were compared with corresponding values of PACVS-affected persons ( N = 191; 159 females; mean/median age: 40/39 years) exhibiting chronic fatigue/dysautonomia (≥three symptoms for ≥five months after the last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases in 11 receptor antibodies (by 25-50%, p < 0.0001), increases in two receptor antibodies (by 15-25%, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly ( p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p < 0.0001) by increased Angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/mL, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/mL, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/mL, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers.

Introduction: Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease., Objectives: To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease., Methodology: To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019., Results: There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; n = 556), followed by patients with primary sclerosing cholangitis (PSC; n = 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P  < 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P  = 0.02, P  < 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P  < 0.001)., Conclusion: Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The rapid evolution of new SARS-CoV-2 variants poses a continuing threat to human health. Vaccination has become the primary therapeutic intervention. The goal of the current work was the construction of immunogenic virus-like particles (VLPs). Here, we describe a human cell line for cost-efficient and scalable production of immunogenic SARS-CoV-2 VLPs. The modular design of the VLP-production platform facilitates rapid adaptation to new variants. Methods: The N, M-, and E-protein genes were integrated into the genome of Expi293 cells (ExpiVLP&#95;MEN). Subsequently, this cell line was further modified for the constitutive expression of the SARS-CoV-2 spike protein. The resulting cell line (ExpiVLP&#95;SMEN) released SARS-CoV-2 VLP upon exposure to doxycycline. ExpiVLP&#95;SMEN cells were readily adapted for VLP production in a 5 L bioreactor. Purified VLPs were quantified by Western blot, ELISA, and nanoparticle tracking analysis and visualized by electron microscopy. Immunogenicity was tested in mice. Results: The generated VLPs contained all four structural proteins, are within the size range of authentic SARS-CoV-2 virus particles, and reacted strongly and specifically with immunoserum from naturally infected individuals. The VLPs were stable in suspension at 4 °C for at least 10 weeks. Mice immunized with VLPs developed neutralizing antibodies against lentiviruses pseudotyped with the SARS-CoV-2 spike protein. The flexibility of the VLP-production platform was demonstrated by the rapid switch of the spike protein to a new variant of concern (BA.1/Omicron). The present study describes an efficient, scalable, and adaptable production method of immunogenic SARS-CoV-2 VLPs with therapeutic potential.

Objective: To describe the clinical presentation, diagnostic imaging findings, surgical technique, histopathological diagnosis, and postoperative outcome in 3 cats with extensive vaginal masses., Animals: Medical records of cats diagnosed with vaginal masses that had a bilateral pubic and ischial osteotomy and vaginectomy between 2004 and 2022 were retrospectively reviewed. Three cats met the inclusion criteria., Clinical Presentation: Histopathological diagnosis included T-cell-rich B-cell lymphoma (n = 1), mycetoma (1), and vaginal polyp (1). Diagnostic imaging included CT (n = 2) and MRI (1), and tumor length/width/height percentages in relation to the pelvic dimensions were 53% X 62% X 63% (case 1), 50% X 100% X 60% (case 2), and 150% X 120% X 120% (case 3). A bilateral pubic and ischial osteotomy was performed in all 3 cases., Results: All 3 cases developed mild pelvic-limb splaying postoperatively; all resolved within 8 weeks, and 2 cases fully resolved within 14 days. Two of the 3 cases presented with mild stranguria postoperatively, which resolved fully in both cases., Clinical Relevance: Vaginal neoplasia, either malignant or benign, is infrequently reported in cats in the veterinary literature. Bilateral pubic and ischial osteotomy for resection of vaginal masses in cats is a successful surgical approach, offering good exposure for resection of large vaginal masses, with minimal postoperative complications.

G protein-coupled receptors (GPCR) are involved in various physiological and pathophysiological processes. Functional autoantibodies targeting GPCRs have been associated with multiple disease manifestations in this context. Here we summarize and discuss the relevant findings and concepts presented in the biennial International Meeting on autoantibodies targeting GPCRs (the 4th Symposium), held in Lübeck, Germany, 15-16 September 2022. The symposium focused on the current knowledge of these autoantibodies' role in various diseases, such as cardiovascular, renal, infectious (COVID-19), and autoimmune diseases (e.g., systemic sclerosis and systemic lupus erythematosus). Beyond their association with disease phenotypes, intense research related to the mechanistic action of these autoantibodies on immune regulation and pathogenesis has been developed, underscoring the role of autoantibodies targeting GPCRs on disease outcomes and etiopathogenesis. The observation repeatedly highlighted that autoantibodies targeting GPCRs could also be present in healthy individuals, suggesting that anti-GPCR autoantibodies play a physiologic role in modeling the course of diseases. Since numerous therapies targeting GPCRs have been developed, including small molecules and monoclonal antibodies designed for treating cancer, infections, metabolic disorders, or inflammatory conditions, anti-GPCR autoantibodies themselves can serve as therapeutic targets to reduce patients' morbidity and mortality, representing a new area for the development of novel therapeutic interventions., (Copyright © 2023. Published by Elsevier B.V.)

This study measures patient's concordance between clinical reference pathways with survival or cost among a population-based cohort of colon cancer patients applying a continuous measure of concordance. The primary hypothesis is that a higher concordance score with the clinical pathway is significantly associated with longer survival or lower cost. The study informs whether patient's adherence to a defined clinical pathway is beneficial to patients' outcomes or health system. An externally determined clinical pathway for colon cancer was used to identify treatment nodes in colon cancer care. Using observational data up to 2019, the study generated a continuous measure of pathway concordance. The study measured whether incremental improvements in pathway concordance were associated with survival and treatment costs. Concordance between patients' reference pathways and their observed trajectories of care was highly statistically associated with survivorship [hazard ratio: 0.95 (95% confidence interval, CI, 0.95-0.96)], showing that adherence to the clinical pathway was associated with a lower mortality rate. An increase in concordance was statistically significantly associated with a decrease in health system cost. When patients' care followed the clinical pathway, survival outcomes were better and total health system costs were lower in this cohort. This finding creates a compelling case for further research into understanding the barriers to pathway concordance and developing interventions to improve outcomes and help providers implement best practice care where appropriate., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care.)

Background: Breast cancer is the most common cancer among women, but most cancer registries do not capture recurrences. We estimated the incidence of local, regional, and distant recurrences using administrative data., Methods: Patients diagnosed with stage I-III primary breast cancer in Ontario, Canada from 2013 to 2017 were included. Patients were followed until 31/Dec/2021, death, or a new primary cancer diagnosis. We used hospital administrative data (diagnostic and intervention codes) to identify local recurrence, regional recurrence, and distant metastasis after primary diagnosis. We used logistic regression to explore factors associated with developing a distant metastasis., Results: With a median follow-up 67 months, 5,431/45,857 (11.8%) of patients developed a distant metastasis a median 23 (9, 42) months after diagnosis of the primary tumor. 1086 (2.4%) and 1069 (2.3%) patients developed an isolated regional or a local recurrence, respectively. Patients with distant metastatic disease had a median overall survival of 15.4 months (95% CI 14.4-16.4 months) from the time recurrence/metastasis was identified. In contrast, the median survival for all other patients was not reached. Patients were more likely to develop a distant metastasis if they had more advanced stage, greater comorbidity, and presented with symptoms (p < 0.0001). Trastuzumab halved the risk of recurrence [OR 0.53 (0.45-0.63), p < 0.0001]., Conclusion: Distant metastasis is not a rare outcome for patients diagnosed with breast cancer, translating to an annual incidence of 2132 new cases (17.8% of all breast cancer diagnoses). Overall survival remains high for patients with locoregional recurrences, but was poor following a diagnosis of a distant metastasis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Precise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage of Drosophila neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here, we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale. We are releasing aligned images of 74,000 such adult central nervous systems. An anticipated use of this resource is to bridge the gap between neurons identified by electron or light microscopy. Identifying individual neurons that make up each GAL4 expression pattern improves the prediction of split-GAL4 combinations targeting particular neurons. To this end, we have made the images searchable on the NeuronBridge website. We demonstrate the potential of NeuronBridge to rapidly and effectively identify neuron matches based on morphology across imaging modalities and datasets., Competing Interests: GM, AN, ZD, GD, KF, TG, JH, YH, NI, JJ, LJ, RJ, KL, BM, BY, CZ, JC, CG, HO, KR, RS, YA, GC, BD, EE, JG, MI, DK, WK, LM, RM, SN, GR, GS, TW, OM No competing interests declared, (© 2023, Meissner et al.)

In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. https://bit.ly/3pqM9Vv., Competing Interests: Conflict of Interest: T. Bahmer reports grants from BMBF (unrestricted research grant for the German Center for Lung Research (DZL) and National Pandemic Cohort Network (NAPKON) – Coordinating Study Site for population-based cohort platform); lecture fees from Novartis, AstraZeneca, and Chiesi; support for attending the American Thoracic Society Conference from Chiesi; and advisory board participation with GlaxoSmithKline, Boehringer Ingelheim, Roche and AstraZeneca, outside the submitted work. D. Frank reports grants from DFG (467267736), BMBF and DZHK; consulting fees and support for attending meetings from Edwards Lifesciences and Medtronic; lecture honoraria from Edwards Lifesciences, Medtronic, Astra Zeneca, Pfizer, BMS, Novartis, Bayer and Abbott; and participation on advisory boards with BMS, Boehringer Ingelheim, Daiichi Sankyo, outside the submitted work. A.Z. Rosenberg reports grants from the NIH (NIDDK and NHLBI) outside the submitted work. CellTrend is owned by K. Schulze-Forster; CellTrend produces ELISA kits for the determination of antibodies against GPCR. G. Riemekasten reports consulting fees from CellTrend GmbH outside the submitted work. S. Schreiber reports consulting fees from Abbvie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Prevention Bio, Protagonist and Falk, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2022.)

A key in controlling the SARS-CoV-2 pandemic is the assessment of the immune status of the population. We explored the utility of SARS-CoV-2 virus-like particles (VLPs) as antigens to detect specific humoral immune reactions in an enzyme-linked immunosorbent assay (ELISA). For this purpose, SARS-CoV-2 VLPs were produced from an engineered cell line and characterized by Western blot, ELISA, and nanoparticle tracking analysis. Subsequently, we collected 42 serum samples from before the pandemic (2014), 89 samples from healthy subjects, and 38 samples from vaccinated subjects. Seventeen samples were collected less than three weeks after infection, and forty-four samples more than three weeks after infection. All serum samples were characterized for their reactivity with VLPs and the SARS-CoV-2 N- and S-protein. Finally, we compared the performance of the VLP-based ELISA with a certified in vitro diagnostic device (IVD). In the applied set of samples, we determined a sensitivity of 95.5% and a specificity of 100% for the certified IVD. There were seven samples with an uncertain outcome. Our VLP-ELISA demonstrated a superior performance, with a sensitivity of 97.5%, a specificity of 100%, and only three uncertain outcomes. This result warrants further research to develop a certified IVD based on SARS-CoV-2 VLPs as an antigen.

Clinical pathways are standardized processes that outline the steps required for managing a specific disease. However, patient pathways often deviate from clinical pathways. Measuring the concordance of patient pathways to clinical pathways is important for health system monitoring and informing quality improvement initiatives. In this paper, we develop an inverse optimization-based approach to measuring pathway concordance in breast cancer, a complex disease. We capture this complexity in a hierarchical network that models the patient's journey through the health system. A novel inverse shortest path model is formulated and solved on this hierarchical network to estimate arc costs, which are used to form a concordance metric to measure the distance between patient pathways and shortest paths (i.e., clinical pathways). Using real breast cancer patient data from Ontario, Canada, we demonstrate that our concordance metric has a statistically significant association with survival for all breast cancer patient subgroups. We also use it to quantify the extent of patient pathway discordances across all subgroups, finding that patients undertaking additional clinical activities constitute the primary driver of discordance in the population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Older adults with cancer may not receive the same opportunities for treatment as younger patients. In this retrospective population-based cohort study, we explored whether age was an independent predictor of receiving specialist consultation and treatment., Methods: Patients age 45-99 were identified from the Ontario Cancer Registry having a primary solid tumor diagnosed between 01/Jan/2010 and 31/Dec/2019. We used logistic regression adjusted sociodemographic and clinical characteristics to compare the likelihood of consultation or receipt of treatment using linear splines at critical ages of 65, 80, and 90 years., Results: A total 168,232 (42%), 165,205 (41%), 57,360 (14%), and 7810 (2%) patients were diagnosed age 45-64, 65-79, 80-89, and 90-99, respectively. The likelihood of surgical consultation decreased as patients reached 65 years [adjusted odds ratio (aOR) 0.86 (0.84-0.89)], which decreased further among octogenarians [aOR 0.63 (0.59-0.67)]. Similar results were observed for consultation with a medical oncologist and radiation oncologist. Receipt of surgery also decreased with age. Three-month post-operative mortality was higher among older patients [aRR 1.38 (1.26-1.50) per 10 years, p < 0.0001], an effect that remained similar as patients reached age 65 + years of age (p = 0.09 for change). For stage I patients, 3-month post-operative survival was high across all age groups, ranging from 99.8% in 45-64 year-olds, 99.4% in 65-79 year-olds, and 98.1% among octogenarians and nonagenarians (lung, colorectal, breast, cervical cancer patients)., Conclusion: Older patients were less likely to have specialist consultations. More comprehensive data collection on clinical factors and referral patterns is needed to improve care for elderly cancer patients., Competing Interests: Conflicts of interest Dr. Ines B. Menjak has some consultancy/honoraria for companies related to lung cancer: Amgen, Astrazeneca. Honoraria for speaking from BMS and Astrazeneca. Education funding from Takeda, Astrazeneca, BMS. All other coauthors have no conflicts to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Most patients with Post COVID Syndrome (PCS) present with a plethora of symptoms without clear evidence of organ dysfunction. A subset of them fulfills diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Symptom severity of ME/CFS correlates with natural regulatory autoantibody (AAB) levels targeting several G-protein coupled receptors (GPCR). In this exploratory study, we analyzed serum AAB levels against vaso- and immunoregulatory receptors, mostly GPCRs, in 80 PCS patients following mild-to-moderate COVID-19, with 40 of them fulfilling diagnostic criteria of ME/CFS. Healthy seronegative (n=38) and asymptomatic post COVID-19 controls (n=40) were also included in the study as control groups. We found lower levels for various AABs in PCS compared to at least one control group, accompanied by alterations in the correlations among AABs. Classification using random forest indicated AABs targeting ADRB2, STAB1, and ADRA2A as the strongest classifiers (AABs stratifying patients according to disease outcomes) of post COVID-19 outcomes. Several AABs correlated with symptom severity in PCS groups. Remarkably, severity of fatigue and vasomotor symptoms were associated with ADRB2 AAB levels in PCS/ME/CFS patients. Our study identified dysregulation of AAB against various receptors involved in the autonomous nervous system (ANS), vaso-, and immunoregulation and their correlation with symptom severity, pointing to their role in the pathogenesis of PCS., Competing Interests: The authors declare that HH and KS-F are managing directors of CellTrend. CellTrend holds together with Charité a patent for the diagnostic use of AABs against ADRB2. CS has a consulting agreement with CellTrend. FP reports grants from the Guthy Jackson Charitable Foundation, during the conduct of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MD declared a past co-authorship with the author YS., (Copyright © 2022 Sotzny, Filgueiras, Kedor, Freitag, Wittke, Bauer, Sepúlveda, Mathias da Fonseca, Baiocchi, Marques, Kim, Lange, Plaça, Luebber, Paulus, De Vito, Jurisica, Schulze-Forster, Paul, Bellmann-Strobl, Rust, Hoppmann, Shoenfeld, Riemekasten, Heidecke, Cabral-Marques and Scheibenbogen.)

Objective: To determine contributions and functions of autoantibodies (Abs) directed to the angiotensin receptor type 1 (AT1R), which are suggested to be involved in the pathogenesis of AT1R Abs-related diseases such as systemic sclerosis (SSc)., Methods: C57BL/6J mice were immunised with membrane-embedded human AT1R or empty membrane as control. Mice deficient for CD4 + or CD8 + T cells and B cells were immunised with membrane-embedded AT1R or an AT1R peptide proposed to be a dominant T cell epitope. A monoclonal (m)AT1R Ab was generated by hybridoma technique and transferred into C57BL/6J and AT1Ra/b knockout mice. The induced phenotype was examined by histology, immunohistochemistry, immunofluorescence, apoptosis assay and ELISA. In vitro, Abs responses towards AT1R were measured in cells of different origins and species., Results: AT1R-immunised mice developed perivascular skin and lung inflammation, lymphocytic alveolitis, weak lung endothelial apoptosis and skin fibrosis accompanied by Smad2/3 signalling, not present in controls or mice deficient for CD4 + T and B cells. The AT1R peptide 149-172 provoked lung inflammation. Application of the mAT1R Ab induced skin and lung inflammation, not observed in AT1Ra/b knockout mice. In vitro, AT1R Abs activated rat cardiomyocytes and human monocytes, enhanced angiotensin II-mediated AT1R activation in AT1R-transfected HEK293 cells via AT1R binding and mAT1R Ab-activated monocytes mediated the induction of profibrotic markers in dermal fibroblasts., Conclusion: Our immunisation strategy successfully induced AT1R Abs, contributing to inflammation and, possibly, to fibrosis via activation of AT1R. Therefore, AT1R Abs are valuable targets for future therapies of SSc and other AT1R Ab-related diseases., Competing Interests: Competing interests: HH is the owner and GR is an advisor of the company CellTrend GmbH, which produced the ME and the tests for the detection of AT1R Abs. IS and GW are shareholders of Berlin Cures GmbH, where the rat cardiomyocyte assay was performed., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a "second breast cancer event") using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm's diagnostic accuracy against a manual patient record review ( n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm's performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures.

Clinical cancer pathways help standardize healthcare delivery to optimize patient outcomes and health system costs. However, population-level measurement of concordance between standardized pathways and actual care received is lacking. Two measures of pathway concordance were developed for a simplified colon cancer pathway map for Stage II-III colon cancer patients in Ontario, Canada: a cumulative count of concordant events (CCCE) and the Levenshtein algorithm. Associations of concordance with patient survival were estimated using Cox proportional hazards models adjusted for patient characteristics and time-dependent cancer-related activities. Models were compared and the impact of including concordance scores was quantified using the likelihood ratio chi-squared test. The ability of the measures to discriminate between survivors and decedents was compared using the C-index. Normalized concordance scores were significantly associated with patient survival in models for cancer stage-a 10% increase in concordance for Stage II patients resulted in a CCCE score adjusted hazard ratio (aHR) of death of 0.93, 95% CI 0.88-0.98 and a Levenshtein score aHR of 0.64, 95% CI 0.60-0.67. A similar relationship was found for Stage III patients-a 10% increase in concordance resulted in a CCCE aHR of 0.85, 95% CI 0.81-0.88 and a Levenshtein aHR of 0.78, 95% CI, 0.74-0.81. Pathway concordance can be used as a tool for health systems to monitor deviations from established clinical pathways. The Levenshtein score better characterized differences between actual care and clinical pathways in a population, was more strongly associated with survival and demonstrated better patient discrimination., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

We propose Rhythmic Relating for autism: a system of supports for friends, therapists, parents, and educators; a system which aims to augment bidirectional communication and complement existing therapeutic approaches. We begin by summarizing the developmental significance of social timing and the social-motor-synchrony challenges observed in early autism. Meta-analyses conclude the early primacy of such challenges, yet cite the lack of focused therapies. We identify core relational parameters in support of social-motor-synchrony and systematize these using the communicative musicality constructs: pulse ; quality ; and narrative . Rhythmic Relating aims to augment the clarity, contiguity, and pulse-beat of spontaneous behavior by recruiting rhythmic supports (cues, accents, turbulence) and relatable vitality; facilitating the predictive flow and just-ahead-in-time planning needed for good-enough social timing. From here, we describe possibilities for playful therapeutic interaction, small-step co-regulation, and layered sensorimotor integration. Lastly, we include several clinical case examples demonstrating the use of Rhythmic Relating within four different therapeutic approaches (Dance Movement Therapy, Improvisational Music Therapy, Play Therapy, and Musical Interaction Therapy). These clinical case examples are introduced here and several more are included in the Supplementary Material (Examples of Rhythmic Relating in Practice). A suite of pilot intervention studies is proposed to assess the efficacy of combining Rhythmic Relating with different therapeutic approaches in playful work with individuals with autism. Further experimental hypotheses are outlined, designed to clarify the significance of certain key features of the Rhythmic Relating approach., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Daniel, Wimpory, Delafield-Butt, Malloch, Holck, Geretsegger, Tortora, Osborne, Schögler, Koch, Elias-Masiques, Howorth, Dunbar, Swan, Rochat, Schlochtermeier, Forster and Amos.)

Objectives: To describe the clinical presentation, management and outcome of cases presenting with intrathoracic wooden skewers originating from the abdominal gastrointestinal tract., Materials and Methods: Clinical records of dogs presented and treated for an intrathoracic wooden skewer were reviewed from June to August 2020. Data included signalment, clinical presentation, duration of clinical signs, haematological and biochemical abnormalities, diagnostic imaging findings, surgical procedure, postoperative complications and outcome., Results: Eleven dogs were included in the study. In all cases, the foreign body was identified as a wooden skewer. The most common clinical signs were anorexia/hyporexia (n=7), vomiting/regurgitation (n=7), lethargy (n=6), pyrexia (n=4) and gait abnormalities/lameness (n=3). CT correctly identified a wooden skewer in all cases when performed (n=7). A coeliotomy combined with transdiaphragmatic thoracotomy was performed in six of 11 cases (55%), a coeliotomy combined with median sternotomy in four of 11 cases (36%) and a median sternotomy alone was performed in one case. Foreign bodies penetrated from the stomach (n=10) or the duodenum (n=1). Intrathoracic trauma was most commonly identified to the lungs (n=3) and pericardium (n=3). Complications occurred in three of 11 cases (27%), two minor and one resulting in death. Ten of the 11 cases (91%) survived to discharge. Long-term outcome was available for seven of 11 cases (66%), all of them excellent., Clinical Significance: Despite the challenges of managing wooden skewers penetrating the thoracic cavity from the abdominal gastrointestinal tract, the majority of the patients are stable to undergo diagnostic procedures, surgical exploration and management with low morbidity and excellent short- and long-term prognosis., (© 2022 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Background: In Ontario, patients with breast cancer typically receive their diagnoses through the Ontario Breast Screening Program (OBSP) after an abnormal screen, through screening initiated by a primary care provider or other referring physician, or through follow-up of symptoms by patients' primary care providers. We sought to explore the association of the route to diagnosis (screening within or outside the OBSP or via symptomatic presentation) with use of OBSP-affiliated breast assessment sites (O-BAS), wait times until diagnosis or treatment, health care use and overall survival for patients with breast cancer., Methods: In this retrospective cohort study, we used the Ontario Cancer Registry to identify adults (aged 18-105 yr) who received a diagnosis of breast cancer from 2013 to 2017. We excluded patients if they were not Ontario residents or had missing age or sex, or who died before diagnosis. We used logistic regression to evaluate factors associated with categorical variables (whether patients were or were not referred to an OBAS, whether patients were screened or symptomatic) and Cox proportional hazards regression to identify factors associated with all-cause mortality., Results: Of 51 460 patients with breast cancer, 42 598 (83%) received their diagnoses at an O-BAS. Patients whose cancer was first detected through the OBSP were more likely than symptomatic patients to be given a diagnosis at an O-BAS (adjusted odds ratio 1.68, 95% confidence interval [CI] 1.57 to 1.80). Patients screened by the OBSP were given their diagnoses 1 month earlier than symptomatic patients, but diagnosis at an O-BAS did not affect the time until either diagnosis or treatment. Patients referred to an O-BAS had significantly better overall survival than those who were not referred (adjusted hazard ratio 0.73, 95% CI 0.66 to 0.80)., Interpretation: Patients screened through the OBSP were given their diagnoses earlier than symptomatic patients and were more likely to be referred to an O-BAS, which was associated with better survival. Our findings suggest that individuals with signs and symptoms of breast cancer would benefit from similar referral processes, oversight and standards to those used by the OBSP., Competing Interests: Competing interests: Steven Habbous, Esha Homenauth, Andriana Barisic, Sharmilaa Kandasamy, Vicky Majpruz, Katharina Forster, Marta Yurcan, Anna Chiarelli, Claire Holloway and Andrea Eisen are employees or consultants of Ontario Health (Cancer Care Ontario), which funds the Ontario Breast Screening Program. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Purpose: This literature review examines the provision of an education on pharmacologically active complementary and alternative medicines (CAMs), to people with cancer, their carers and oncology health professionals., Methods: A search of the published literature between 2000 and 2020, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, was conducted. The search retrieved 1121 studies, 1080 were excluded based on their title or abstract and 26 articles were excluded based on their text. One article was retrieved from the reference lists of the included articles and in total fifteen studies met the inclusion criteria. This review utilised Medical Education Research Quality Instrument (MERSQI) to evaluate the quality of the included studies. Four key outcomes were utilised for analysis and recommendations for future education and/or research were generated. The recommendations were graded according to the Strength of Recommendation Taxonomy (SORT)., Results: This review consistently found that people with cancer, their carers and oncology health professionals derived benefit from a pharmacologically active CAM education and recommends that this population receives one. Conversely, the review found many education formats utilised and no consensus on the most successful methods., Conclusion: Future research should examine who a CAM education should be delivered to, what type of delivery platform is most accessible and useful, and the features of the education that most increase CAM knowledge. The popularity of CAMs amongst people with cancer and the potential dangers associated with their use necessitates further research into how best to communicate CAMs to this population., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity., (© 2022. The Author(s).)

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

Objectives: To describe the outcome and complications associated with the use of caudal superficial epigastric axial pattern flaps in dogs and cats., Material and Methods: Multicentre retrospective review and descriptive study of clinical records of dogs and cats having undergone caudal superficial epigastric axial pattern flaps between 2007 and 2020. Data retrieved included signalment, aetiology of surgical defect, tumour type, presence/absence of clean surgical margins, presence/absence of post-operative wound infection, use of peri- and post-operative antibiotics, duration of anaesthesia, duration of surgery, presence and duration of hypothermia, presence and duration of hypotension, presence/absence of post-operative surgical drain and length of caudal superficial epigastric axial pattern flap. The incidence of complications and outcomes were documented., Results: Seventy cases met the inclusion criteria; 51 dogs and 19 cats. In dogs, 67% of cases developed complications (59% minor, 8% major) and 33% had uneventful wound healing. In cats, 53% of cases developed complications, (47% minor, 5% major) and 47% had uneventful wound healing. In dogs, the percentage of cases experiencing dehiscence, necrosis, seroma, oedema and post-operative infection was 31%, 29%, 26%, 26% and 16% respectively. In cats, this was 26%, 16%, 11%, 0% and 5% respectively. A good overall outcome was seen in 77% of dogs and 79% of cats. A poor overall outcome was seen in 4% of dogs and 0% of cats., Clinical Significance: Caudal superficial epigastric axial pattern flaps are traditionally thought more robust than other flaps, yet complication rates remain high, despite a high overall success rate., (© 2021 British Small Animal Veterinary Association.)

Background: Pegfilgrastim is a covalently bound conjugate of filgrastim and mono-methoxypolyethylene glycol with a longer half-life., Study Design and Methods: We report on phase II prospective monocentric trial examining the feasibility of stem cell mobilization with 12 mg single dose pegfilgrastim in related donors. The objectives were to determine the optimal collection day, defined as CD34+ concentration in peripheral blood (PB) >50 cells/μl, the number of donors collected with single leukapheresis, and the peak level of pegfilgrastim in donor-serum. Furthermore, the cell composition of grafts was assessed and compared to published data., Results: The results included about 28 matched related donors. The median pegfilgrastim serum level remained >200 ng/mL for 48 hours before declining, with the maximal measured concentration of 259.49 ng/ml 24 h after application. The median white blood cell count and CD34 count in PB peaked on day four with 52.6 (range 22.8-85.0) Gpt/l and 66.25 (range 22.9-136.6) cells/μl, respectively. A CD34+ count >50 cells/μl on day four was detected in 75% of donors. 79% of the donors underwent a single collection. Conventional filgrastim was administered additionally in two donors, due to insufficient CD 34+ concentration in PB. 89% of donors showed CD34+ yields ≥4 (median 6.5, range 4.6-14.5) × 10/kg body weight of the recipient. All grafts were administered without rejections., Discussion: The results of this trial showed that stem cell mobilization with pegfilgrastim is a feasible, and attractive option. This is the first trial presenting the kinetics of pegfilgrastim serum levels in healthy donors., (© 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Complementary and alternative medicine (CAM) usage amongst cancer patients is high globally and in Australia. CAM use in cancer care has the ability to increase chemotherapy toxicity or cause sub-therapy due to altered metabolism as well as increase a patient's bleeding risk. Furthering these risks, people with cancer are largely obtaining their CAM use information from non-evidence-based sources. This study aimed to determine whether the implementation of a CAM education influenced decision-making with regard to CAM usage amongst cancer patients. Twenty people with cancer were recruited for participation in this study. The aims of this study were achieved by surveying patients via questionnaire, both prior to and following receiving an evidence-based CAM education, in either or both written or audiovisual format. This exploratory study found, consistent with the literature, that the majority of participants were obtaining their CAM use information from non-evidenced-based sources. Additionally, it found that the participants wanted more CAM use information and that they demonstrated some altered decision-making after receiving evidenced-based information. On the post-educational questionnaire, the number of participants that stated that they would use CAMs decreased by almost 14%, and some participants made CAM use decisions in accordance with the information provided in the resources. Furthermore, a small increase in CAM knowledge was demonstrated, and it was reported that the resource had prompted them to look further into CAM information. Lastly, the participants in this study found the resource to be mostly useful and helpful and preferred the animated video to the written information., (© 2020. American Association for Cancer Education.)

Importance: Esophageal cancer remains one of the most deadly cancers, ranking sixth highest among cancers leading to the greatest years of life lost., Objective: To determine how patients with esophageal cancer are diagnosed and treated in Ontario's regionalized thoracic surgery centers., Design, Setting, and Participants: This cohort study included patients diagnosed with esophageal cancer between January 1, 2010, and December 31, 2018, identified from the Ontario Cancer Registry, in a single-payer health care system with regionalization of thoracic surgery in the province of Ontario, Canada., Exposures: Exposures included incidence of esophageal cancer and stage at diagnosis; time from the first health care visit until treatment; and the use of specialist consultations, endoscopic ultrasonography, positron emission tomography and computed tomography, endomucosal resection, esophagectomy, neoadjuvant therapy, adjuvant therapy, radiation alone, and chemotherapy alone or in combination with other treatment., Main Outcomes and Measures: Outcome measures included wait times, health care use, treatment, and overall survival. Data were analyzed from March 2020 to February 2021., Results: There were 10 364 patients (mean [SD] age, 68.3 [11.9] years; 7876 men [76%]) identified during the study period. The incidence of esophageal cancer increased over the study period from 1041 in 2010 to 1309 in 2018, which was driven by a 30% increase in the number of adenocarcinomas. The time from first health care encounter to start of treatment was a median 93 days (interquartile range, 56-159 days). Endoscopic ultrasonography was observed for 12% of patients, and positron emission tomography and computed tomography (CT) in 45%. Use of endoscopic mucosal resection was observed for 8% of patients with stage 0 to I disease. A total of 114 of 547 patients (21%) receiving endoscopic resection had a subsequent esophagectomy. Only 2778 patients (27%) had consultations with a thoracic surgeon, a medical oncologist, and a radiation oncologist, whereas 1514 patients (15%) did not see any of these specialists. Of 3047 patients who had an esophagectomy, those receiving neoadjuvant therapy had better overall survival (median survival, 36 months; 95% CI, 32-39 months) than patients who received esophagectomy alone (median survival, 27 months; 95% CI, 24-30 months) or those who received esophagectomy with adjuvant therapy (median survival, 36 months; 95% CI, 32-44 months) despite significant early mortality (log-rank P < .001). There was significant variation in treatment modality across hospitals: esophagectomy ranged from 5% to 39%; esophagectomy after neoadjuvant therapy ranged from 33% to 93%; and esophagectomy followed by adjuvant therapy ranged from 0 to 34% (P < .001). Perioperative mortality was higher at 30 days for patients receiving esophagectomy at low-volume centers (odds ratio [OR], 3.66; 95% CI, 2.01-6.66) and medium-volume centers (OR, 2.07; 95% CI, 1.33-3.23) compared with high-volume centers (P < .001). A longer wait time until treatment was associated with better overall survival (median overall survival was 15 to 17 days vs 5 to 8 days for patients who received treatment earlier than 30 days vs 30 days or longer after diagnosis; P < .001)., Conclusions and Relevance: The results of this cohort study suggest that despite regionalization, there was significant regional variability in volumes at designated centers and in the evaluation and treatment course for patients with esophageal cancer across Ontario.

Forecasting which dyads will develop mutually supportive relationships is an important applied and basic research question. Applying psychometric theory to the design of forecasting studies shows that agreement between dyad members about their relationship (relational reciprocity) sets an upper limit for forecasting accuracy by determining the reliability of measurement. To test this, we estimated relational reciprocity in Study 1. Participants in seven samples (six student and one military; N = 504; N dyads = 766) rated each other on support-related constructs in round-robin designs. Relational reciprocity was very low, undermining reliability. Formulas from psychometric theory predicted that forecasting supportive dyads would be practically impossible. To test this, we had participants in Study 2 complete a measure for matching dyads derived from recent theory. As predicted, supportive matches could not be forecast with acceptable precision. Theoretically, this falsifies some predictions of recent social-support theory. Practically, it remains unclear how to translate basic social-support research into effective interventions.

A key method for studying articulatory planning at different levels of phonological organization is masked-onset priming. In previous work using that paradigm the dependent variable has been acoustic response time (RT). We used electromagnetic articulography to measure articulatory RTs and the articulatory properties of speech gestures in non-word production in a masked-onset priming experiment. Initiation of articulation preceded acoustic response onset by 199 ms, but the acoustic lag varied by up to 63 ms, depending on the phonological structure of the target. Onset priming affected articulatory response latency, but had no effect on gestural duration, inter-gestural coordination, or articulatory velocity. This is consistent with an account of the masked-onset priming effect in which the computation from orthography of an abstract phonological representation of the target is initiated earlier in the primed than in the unprimed condition. We discuss the implications of these findings for models of speech production and the scope of articulatory planning and execution.

There is a global rise in skin cancer incidence, resulting in an increase in patient care needs and healthcare costs. To optimize health care planning, costs, and patient care, Ontario Health developed a provincial skin cancer plan to streamline the quality of care. We conducted a systematic review and a grey literature search to evaluate the definitions and management of skin cancer within other jurisdictions, as well as a provincial survey of skin cancer care practices, to identify care gaps. The systematic review did not identify any published comprehensive skin cancer management plans. The grey literature search revealed skin cancer plans in isolated regions of the United Kingdom (U.K.), National Institute for Health and Care Excellence (NICE) guidelines for skin cancer quality indicators and regional skin cancer biopsy clinics, and wait time guidelines in Australia and the U.K. With the input of the Ontario Cancer Advisory Committee (CAC), unique definitions for complex and non-complex skin cancers and the appropriate cancer services were created. A provincial survey of skin cancer care yielded 44 responses and demonstrated gaps in biopsy access. A skin cancer pathway map was created and a recommendation was made for regional skin cancer biopsy clinics. We have created unique definitions for complex and non-complex skin cancer and a skin cancer pathways map, which will allow for the implementation of both process and performance metrics to address identified gaps in care.

Introduction: Diagnostic assessment programs (DAPs) were implemented in Ontario, Canada, to improve the efficiency of the lung cancer care continuum. We compared the efficiency and effectiveness of care provided to patients in DAPs relative to usual care (non-DAPs)., Methods: Lung cancer patients diagnosed between 2014 and 2016 were identified from the Ontario Cancer Registry. Using administrative databases, we identified various health-care encounters 6 months before diagnosis until the start of treatment and compared utilization patterns, timing, and overall survival between DAP and non-DAP patients., Results: DAP patients were younger ( P < 0.0001), had fewer comorbidities ( P = 0.0006), and were more likely to have early-stage disease (36% vs. 25%) than non-DAP patients. Although DAP patients had a similar time until diagnosis as non-DAP patients, the time until treatment was 8.5 days shorter for DAP patients. DAP patients were more likely to receive diagnostic tests and specialist consultations and less likely to have duplicate chest imaging. DAP patients were more likely to receive brain imaging. Among early-stage lung cancers, brain imaging was high (74% for DAP and 67% for non-DAP), exceeding guideline recommendations. After adjustment for clinical and demographic factors, DAP patients had better overall survival than non-DAP patients (hazard ratio [HR]: 0.79 [0.76-0.82]), but this benefit was lost after adjusting for emergency presentation (HR: 0.96 [0.92-1.00]). A longer time until treatment was associated with better overall survival., Conclusion: DAPs provided earlier treatment and better access to care, potentially improving survival. Quality improvement opportunities include reducing unnecessary or duplicate testing and characterizing patients who are diagnosed emergently., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Thoracic Medicine.)

Background: Although intracranial metastatic disease (IMD) is a frequent complication of cancer, most cancer registries do not capture these cases. Consequently, a data-gap exists, which thwarts system-level quality improvement efforts. The purpose of this investigation was to determine the real-world burden of IMD., Methods: Patients diagnosed with a non-CNS cancer between 2010 and 2018 were identified from the Ontario Cancer Registry. IMD was identified by scanning hospital administrative databases for cranial irradiation or coding for a secondary brain malignancy (ICD-10 code C793)., Results: 25,478 of 601,678 (4.2%) patients with a diagnosis of primary cancer were found to have IMD. The median time from primary cancer diagnosis to IMD was 5.2 (0.7, 15.4) months and varied across disease sites, for example, 2.1 months for lung, 7.3 months for kidney, and 22.8 months for breast. Median survival following diagnosis with IMD was 3.7 months. Lung cancer accounted for 60% of all brain metastases, followed by breast cancer (11%) and melanoma (6%). More advanced stage at diagnosis and younger age were associated with a higher likelihood of developing IMD ( P < .0001). IMD was also associated with triple-negative breast cancers and ductal histology ( P < .001), and with small-cell histology in patients with lung cancer ( P < .0001). The annual incidence of IMD was 3,520, translating to 24.2 per 100,000 persons., Conclusion: IMD represents a significant burden in patients with systemic cancers and is a significant cause of cancer mortality. Our findings support measures to actively capture incidents of brain metastasis in cancer registries., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)