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Purpose/objectives: To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. Methods: A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios. Results: Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1 cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival. Conclusion: These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy.
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Immune cells express an incredible variety of proteins; by measuring combinations of these, cell types influencing disease can be precisely identified. We developed terraFlow, a platform that defines cell subsets exhaustively by combinatorial protein expression. Using high-parameter checkpoint-focused and function-focused panels, we studied classical Hodgkin's lymphoma (cHL), where systemic T cells have not been investigated in detail. terraFlow revealed immune perturbations in patients, including elevated activated, exhausted, and interleukin (IL)-17+ phenotypes, along with diminished early, interferon (IFN)γ+, and tumor necrosis factor (TNF)+ T cells before treatment; many perturbations remained after treatment. terraFlow identified more disease-associated differences than other tools, often with better predictive power, and included a non-gating approach, eliminating time-consuming and subjective manual thresholds. It also reports a method to identify the smallest set of markers distinguishing study groups. Our results provide mechanistic support for past reports of immune deficiency in cHL and demonstrate the value of terraFlow in immunotherapy and biomarker studies.
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L-Idose thioglycosides are useful glycosyl donors for the construction of glycosaminoglycan oligosaccharides. When activated with NIS and catalytic TMSOTf in the presence of methanol, the stereoselectivity of O-glycosylation displays an intriguing dependence on the reaction temperature, with an increased preference for formation of the α-glycoside at higher temperatures. Using a combination of vt-NMR spectroscopy and DFT calculations, we show how a simple mechanistic model, based on competing reactions of the iodinated thioglycoside, can explain the main features of the temperature dependence. In this model, the increased selectivity at high temperature is attributed to differences among the entropy and energy terms of the competing reaction pathways. Neighbouring-group participation (giving an intermediate acyloxonium ion) plays an increasingly dominant role as temperature is raised. The general features of this kinetic regime may also apply more broadly to other glycosylations that likewise favour α-glycoside formation at high temperature.
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Amid the growing demand for sustainable pavement solutions and the need to incorporate recycled materials into construction practices, this study explored the viability of using crushed thermal power plant bottom ash as a filler in polymer-modified asphalt concrete mixtures. Conventional lime filler was replaced with bottom ash at varying levels (0%, 25%, 50%, and 75%), and the resulting mixtures were evaluated using several performance tests. The optimal replacement level was determined to be 25%, based on the results of the indirect tensile strength (ITS) test. Comparisons between the control mixture and the 25% bottom ash-modified mixture were conducted using the dynamic modulus test, Cantabro test, Hamburg wheel tracking (HWT) test, and tensile strength ratio (TSR) test. The findings indicate that the 25% bottom ash-modified mixture demonstrated improved performance across multiple parameters. The HWT test showed enhanced rut durability, with a recorded depth of 7.56 mm compared to 8.9 mm for the control mixture. The Cantabro test results revealed lower weight loss percentages for the modified mixture, indicating better abrasion resistance. The dynamic modulus test indicated higher resilience and stiffness in both high- and low-frequency stages. The TSR test highlighted improved moisture resistance, with higher TSR values after 10 wet-drying cycles. These improvements are attributed to the fine particle size and beneficial chemical composition of bottom ash, which enhance the asphalt mixture's density, binder-aggregate adhesion, and overall durability. The results suggest that incorporating 25% crushed bottom ash as a filler in polymer-modified asphalt concrete mixtures is a viable and sustainable approach to improving pavement performance and longevity.
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In this study, we developed a high-performance non-enzymatic electrochemical sensor based on urchin-like CoP3/Cu3P heterostructured nanorods supported on a three-dimensional porous copper foam, namely, CoP3/Cu3P NRs/CF, for the detection of dopamine. Benefiting from the promising intrinsic catalytic activities of CoP3 and Cu3P, urchin-like microsphere structures, and a large electrochemically active surface area for exposing numerous accessible catalytic active sites, the proposed CoP3/Cu3P NRs/CF shows extraordinary electrochemical response towards the electrocatalytic oxidation of dopamine. As a result, the CoP3/Cu3P NRs/CF sensing electrode has a broad detection window (from 0.2 to 2000 µM), low detection limit (0.51 µM), high electrochemical sensitivity (0.0105 mA µM-1 cm-2), excellent selectivity towards dopamine in the coexistence of some interfering species, and good stability for dopamine determination. More importantly, the CoP3/Cu3P NRs/CF catalyst also exhibits excellent catalytic activity, sensitivity, and selectivity for dopamine detection under simulated human body conditions at a physiological pH of 7.25 (0.1 M PBS) at 36.6 °C.
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Cobre , Dopamina , Técnicas Electroquímicas , Nanotubos , Dopamina/análisis , Dopamina/química , Cobre/química , Técnicas Electroquímicas/métodos , Nanotubos/química , Porosidad , Catálisis , Cobalto/química , Electrodos , Límite de Detección , Oxidación-ReducciónRESUMEN
This manuscript presents a comprehensive study on the sustainable optimization of asphalt mixtures tailored for regions prone to flooding. The research addresses the challenges associated with water damage to asphalt pavements by incorporating innovative additives. The study centers on incorporating recycled Low-Density Polyethylene (LDPE) and a tailored Carnauba-Soybean Oil Additive, advancing asphalt mixtures with a Control mix, LDPE (5%) + Control, and LDPE (5%) + 3% Oil + Control. A critical aspect of the research involves subjecting these mixtures to 30 wetting and drying cycles, simulating the conditions prevalent in tropical flood-prone areas. The incorporation of innovative additives in asphalt mixtures has demonstrated significant improvements across various performance parameters. Tensile Strength Ratio (TSR) tests revealed enhanced tensile strength, with the LDPE (5%) + 3% Oil-modified mixture exhibiting an impressive TSR of 85.7%. Dynamic Modulus tests highlighted improved rutting resistance, showcasing a remarkable increase to 214 MPa in the LDPE (5%) with a 3% Oil-modified mixture. The Semi-Circular Bending (SCB) test demonstrated increased fracture resistance and energy absorption, particularly in the LDPE (5%) with 3% Oil-modified mixture. Hamburg Wheel-Tracking (HWT) tests indicated enhanced moisture resistance and superior rutting resistance at 20,000 cycles for the same mixture. Cantabro tests underscored improved aggregate shatter resistance, with the LDPE (5%) + 3% Oil-modified mixture exhibiting the lowest weight loss rate at 9.820%. Field tests provided real-world insights, with the LDPE (5%) + 3% Oil mixture displaying superior stability, a 61% reduction in deflection, and a 256% improvement in surface modulus over the control mixture. This research lays the groundwork for advancing the development of sustainable, high-performance road pavement materials, marking a significant stride towards resilient infrastructure in flood-prone areas.
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Backgrounds/Aims: Socioeconomic determinants of health are incompletely characterized in cholangiocarcinoma (CCA). We assessed how socioeconomic status influences initial treatment decisions and survival outcomes in patients with CCA, additionally performing multiple sub-analyses based on anatomic location of the primary tumor. Methods: Observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results (SEER)-18 Database. In total, 5,476 patients from 2004-2015 with a CCA were separated based on median household income (MHI) into low income (< 25th percentile of MHI) and high income (> 25th percentile of MHI) groups. Seventy-three percent of patients had complete follow up data, and were included in survival analyses. Survival and treatment outcomes were calculated using R-studio. Results: When all cases of CCA were included, the high-income group was more likely than the low-income to receive surgery, chemotherapy, and local tumor destruction modalities. Initial treatment modality based on income differed significantly between tumor locations. Patients of lower income had higher overall and cancer-specific mortality at 2 and 5 years. Non-cancer mortality was similar between the groups. Survival differences identified in the overall cohort were maintained in the intrahepatic CCA subgroup. No differences between income groups were noted in cancer-specific or overall mortality for perihilar tumors, with variable differences in the distal cohort. Conclusions: Lower income was associated with higher rates of cancer-specific mortality and lower rates of surgical resection in CCA. There were significant differences in treatment selection and outcomes between intrahepatic, perihilar, and distal tumors. Population-based strategies aimed at identifying possible etiologies for these disparities are paramount to improving patient outcomes.
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Introduction: Healthcare workers (HCWs) often experience morally challenging situations in their workplaces that may contribute to job turnover and compromised well-being. This study aimed to characterize the nature and frequency of moral stressors experienced by HCWs during the COVID-19 pandemic, examine their influence on psychosocial-spiritual factors, and capture the impact of such factors and related moral stressors on HCWs' self-reported job attrition intentions.Methods: A sample of 1204 Canadian HCWs were included in the analysis through a web-based survey platform whereby work-related factors (e.g. years spent working as HCW, providing care to COVID-19 patients), moral distress (captured by MMD-HP), moral injury (captured by MIOS), mental health symptomatology, and job turnover due to moral distress were assessed.Results: Moral stressors with the highest reported frequency and distress ratings included patient care requirements that exceeded the capacity HCWs felt safe/comfortable managing, reported lack of resource availability, and belief that administration was not addressing issues that compromised patient care. Participants who considered leaving their jobs (44%; N = 517) demonstrated greater moral distress and injury scores. Logistic regression highlighted burnout (AOR = 1.59; p < .001), moral distress (AOR = 1.83; p < .001), and moral injury due to trust violation (AOR = 1.30; p = .022) as significant predictors of the intention to leave one's job.Conclusion: While it is impossible to fully eliminate moral stressors from healthcare, especially during exceptional and critical scenarios like a global pandemic, it is crucial to recognize the detrimental impacts on HCWs. This underscores the urgent need for additional research to identify protective factors that can mitigate the impact of these stressors.
This study explored the nature of moral stressors encountered by health care workers, along with impacts on moral injury and intentions to leave their jobs.Morally distressing encounters were common, with the most prevalent and distressing experiences being organizational or team-based in nature.Findings revealed that severity of moral injury, particularly related to trust violation or betrayal, was a key factor influencing healthcare workers' intentions to leave their jobs.
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COVID-19 , Pandemias , Humanos , Prevalencia , Canadá/epidemiología , Principios Morales , COVID-19/epidemiología , Personal de SaludRESUMEN
PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapéutico , Leucocitos Mononucleares/patología , Neoplasias Encefálicas/genética , Linfocitos T/patología , Glioblastoma/tratamiento farmacológico , Receptores ErbB , Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos Alquilantes/farmacologíaRESUMEN
As mobile and wearable devices continue to grow in popularity, there is strong yet unrealized potential to harness people's mobile sensing data to improve our understanding of their cellular and biologically-based diseases. Breakthrough technical innovations in tumor modeling, such as the three dimensional tumor microenvironment system (TMES), allow researchers to study the behavior of tumor cells in a controlled environment that closely mimics the human body. Although patients' health behaviors are known to impact their tumor growth through circulating hormones (cortisol, melatonin), capturing this process is a challenge to rendering realistic tumor models in the TMES or similar tumor modeling systems. The goal of this paper is to propose a conceptual framework that unifies researchers from digital health, data science, oncology, and cellular signaling, in a common cause to improve cancer patients' treatment outcomes through mobile sensing. In support of our framework, existing studies indicate that it is feasible to use people's mobile sensing data to approximate their underlying hormone levels. Further, it was found that when cortisol is cycled through the TMES based on actual patients' cortisol levels, there is a significant increase in pancreatic tumor cell growth compared to when cortisol levels are at normal healthy levels. Taken together, findings from these studies indicate that continuous monitoring of people's hormone levels through mobile sensing may improve experimentation in the TMES, by informing how hormones should be introduced. We hope our framework inspires digital health researchers in the psychosocial sciences to consider how their expertise can be applied to advancing outcomes across levels of inquiry, from behavioral to cellular.
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Rising traffic volume, heavy loads, and construction activities have raised concerns about expansion joint device damage. This study focuses on developing an innovative expansion joint using polymer-modified rubber asphalt as the filling material to enhance its service life. Styrene-butadiene-styrene (SBS) emerged as a suitable modifier for rubber-modified asphalt, significantly improving elasticity and adhesion. Through the strategic combination of 3- and 2-block linear SBS, the elasticity and adhesion properties were significantly improved, resulting in the formulation of a well-suited polymer-modified rubber asphalt binder. The developed asphalt binder exhibits impressive elastic recovery (61.1% to 66.1%), surpassing commercial products, with enhanced constructability and workability (15% to 21% viscosity reduction). The carefully engineered mastic asphalt mixture showcases self-leveling characteristics at a moderate 210 °C, addressing historical constructability challenges. Settlement is 40% less than traditional hot mix asphalt for surface layers, with improved moisture and stripping resistance, enhancing existing asphalt plug joint durability and workability. Collectively, this novel mixture, comprising polymer-modified rubber and mastic asphalt, showcases the potential to enhance the durability of existing asphalt plug joints while ensuring superior constructability and workability.
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OBJECTIVE: Canadian Armed Forces (CAF) members and Veterans are more likely to experience mental health (MH) conditions, such as posttraumatic stress disorder (PTSD), than the general Canadian population. Previous research suggests that an increasing number of individuals are employing cannabis for MH symptom relief, despite a lack of robust evidence for its effectiveness in treating PTSD. This research aimed to: (1) describe the prevalence of current cannabis use among MH treatment-seeking CAF members and Veterans; and (2) estimate the association between current cannabis use and a number of sociodemographic, military, and MH-related characteristics. METHOD: Using cross-sectional intake data from 415 CAF members and Veterans attending a specialized outpatient MH clinic in Ontario, Canada, between January 2018 and December 2020, we estimated the proportion of CAF members and Veterans who reported current cannabis use for either medical or recreational purposes. We used multivariable logistic regression to estimate adjusted odds ratios for a number of sociodemographic, military, and MH-related variables and current cannabis use. RESULTS: Almost half of the study participants (n = 187; 45.1%) reported current cannabis use. Respondents who reported current cannabis use for medical purposes had a higher median daily dose than those who reported current cannabis use for recreational purposes. The multivariable logistic regression identified younger age, lower income, potentially hazardous alcohol use, and increased bodily pain as statistically significant correlates of current cannabis use among our MH treatment-seeking sample. PTSD severity, depressive severity, sleep quality, and suicide ideation were not statistically associated with current cannabis use. CONCLUSIONS: Almost half of our treatment-seeking sample reported current cannabis use for medical or recreational purposes, emphasizing the importance of screening MH treatment-seeking military members and Veterans for cannabis use prior to commencing treatment. Future research building upon this study could explore the potential impact of cannabis use on MH outcomes.
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Cannabis , Personal Militar , Trastornos por Estrés Postraumático , Veteranos , Humanos , Veteranos/psicología , Salud Mental , Estudios Transversales , Personal Militar/psicología , Trastornos por Estrés Postraumático/psicología , Ontario/epidemiologíaRESUMEN
This research investigates the quantitative impact of incorporating epoxy resin and crumb rubber powder (CRP) into cement asphalt mortar (CAM) for railway track stabilization. The study reveals significant improvements in various key parameters compared to conventional CAM. The modified CAM exhibits a 12.7% reduction in flow time, indicative of enhanced flowability, and a substantial 62.4% decrease in the mixing stability gap, demonstrating superior mixing stability. Additionally, the modified CAM displays remarkable early-age compressive strength, with increases of up to 15.3% compared to traditional CAM formulations. Importantly, the modified CAM showcases robust resistance to challenging environmental conditions, with only a 6.7% strength reduction after exposure to sulfuric acid, highlighting its acid resistance, and exceptional freeze-thaw resistance, with a mere 1.5% strength reduction after undergoing six cycles. In a mock-up test simulating real-world conditions, the modified CAM effectively prevents ballast layer settlement, underscoring its potential to enhance the durability of railway track infrastructure. These quantitative findings not only endorse the practical feasibility of epoxy resin and CRP-enhanced CAM but also suggest its potential to contribute significantly to railway track longevity, reduce maintenance expenditures, and ensure operational reliability.
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Introduction: The COVID-19 pandemic has resulted in heightened moral distress among health care workers (HCWs) worldwide. Past research has shown that effective leadership may mitigate potential for the development of moral distress. However, no research to date has considered the mechanisms by which leadership might have an influence on moral distress. We sought to evaluate longitudinally whether Canadian HCWs' perceptions of workplace support and ethical work environment would mediate associations between leadership and moral distress. Methods: A total of 239 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in a longitudinal online survey. Participants completed measures of organizational and supervisory leadership at baseline and follow-up assessments of workplace support, perceptions of an ethical work environment, and moral distress. Results: Associations between both organizational and supervisory leadership and moral distress were fully mediated by workplace supports and perceptions of an ethical work environment. Discussion: To ensure HCW well-being and quality of care, it is important to ensure that HCWs are provided with adequate workplace supports, including manageable work hours, social support, and recognition for efforts, as well as an ethical workplace environment.
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Colchicine myopathy typically presents acutely to subacutely with progressive limb weakness. The patients may not be on high doses of colchicine but almost always have acute kidney injury. Dehydration from colchicine-induced diarrhoea is often a precipitating factor. The concomitant neurotoxicity may produce mild sensory complaints. This combination of acute neurological symptoms preceded by diarrhoea prompts the diagnosis of Guillain-Barre syndrome (GBS). The absence of cranial nerve deficits, raised creatine kinase and myotonic discharges on electromyogram may help in differentiating this condition from GBS. We describe a clinical sign, myoedema - a mounding phenomenon of muscle that is elicited by percussion and resolves when the patient recovers. It aids in the bedside diagnosis of acute colchicine myopathy as well as distinguish it from other more common causes of acute flaccid paralysis. We also discuss the possible mechanism of colchicine toxicity and the mounding phenomenon.
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Síndrome de Guillain-Barré , Enfermedades Musculares , Enfermedades Neuromusculares , Humanos , Colchicina/efectos adversos , Enfermedades Musculares/inducido químicamente , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/complicaciones , Enfermedades Neuromusculares/inducido químicamente , Síndrome de Guillain-Barré/diagnóstico , Diarrea/inducido químicamenteRESUMEN
Aim: Ovarian cancer is a serious malignancy with high prevalence and mortality. Methods: We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. Results: The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4 cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67 markers. Conclusion: We have successfully isolated and characterized the M4 cell line from a Vietnamese patient with ovarian carcinoma.
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This research addresses the urgent need for sustainable and durable asphalt mixtures by quantitatively investigating the effects of incorporating waste plastic aggregate (WPA) and magnesium-based additives. This study explores WPA content levels of 3%, 5%, and 7% wt of aggregate in combination with a fixed 3% wt epoxy resin content to the asphalt binder, supplemented with the 1.5% wt magnesium-based additive. The novelty of this research lies in its comprehensive analysis of various performance parameters, including deformation strength, indirect tensile strength (ITS), rut depth, and dynamic stability, to assess the impact of WPA, epoxy resin, and the magnesium-based additive on asphalt mixture properties. The results demonstrate significant improvements in key performance aspects with increasing WPA content. The WPA mixtures exhibit enhanced deformation strength, with values of 4.01, 3.7, and 3.32 MPa for 3, 5, and 7% wt WPA content, respectively, compared to the control mixture. Furthermore, the inclusion of WPA and epoxy resin, along with the magnesium-based additive, contributes to improved adhesion, cohesion, and resistance to stripping damage. Notably, the 7% wt WPA mixture showcases exceptional performance, characterized by a final rut depth of 2.66 mm and a dynamic stability of 7519 passes per millimeter, highlighting its superior rutting resistance and load-bearing capacity. This study also reveals the influence of WPA content on ITS and stiffness properties, with the 5% wt WPA mixture achieving an optimal balance between strength and stiffness. Overall, this research highlights the potential of incorporating WPA, epoxy resin, and magnesium-based additives in asphalt mixtures to enhance their performance and durability. By utilizing plastic waste materials and optimizing their combination with epoxy reinforcement, along with the innovative use of magnesium-based additive, the findings contribute to the development of sustainable infrastructure materials and pave the way for further advancements in the field.
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PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Adulto Joven , Adolescente , Persona de Mediana Edad , Estudios Retrospectivos , Colangiocarcinoma/genética , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/patología , BiologíaRESUMEN
PURPOSE: This study used ecological momentary assessment (EMA) to test the association between activity, location, and social company contexts with cancer caregivers' in-the-moment affect to identify precisely when and where to deliver psychological interventions for caregivers. METHODS: Current cancer caregivers (N = 25) received 8 EMA prompts per day for 7 consecutive days. At each prompt, caregivers reported their current positive affect and negative affect, as well as what they were doing, where they were located, and who they were with. Multilevel logistic regressions tested the associations between caregivers' contexts with their own person-mean-centered state (concurrent momentary level) and trait (overall weekly average) positive or negative affect. RESULTS: Caregivers reported lower state negative affect, as well as higher state positive affect, when socializing (ps < .001), when at a public location (ps < .03), and when around their friends, family, spouse/partner, or care recipient (i.e., person with cancer, ps < .02), relative to when not endorsing the context. Caregivers also reported lower state negative affect when eating/drinking or engaging in leisure (ps < .01; but no parallel effects for state positive affect). Caregivers reported higher state negative affect while working, when at their workplace, or when around work colleagues (ps < .001) and lower state positive affect when at home or alone (ps < .03). CONCLUSIONS: Results suggest the pertinence of a behavioral activation framework to mitigate the emotional strain of caregiving. Interventions that facilitate caregivers' ability to socialize with a range of friends and family, including their loved one with cancer, outside of the home may have the strongest positive emotional impact.
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Cuidadores , Neoplasias , Humanos , Neoplasias/terapia , Terapia Conductista , Emociones , AmigosRESUMEN
This study addresses the challenges of overlaying old concrete pavement with asphalt by introducing a new trackless tack coat material containing polymer. The aim is to enhance the durability of asphalt concrete overlay pavement on old cement concrete pavement. It contributes to the development of improved construction techniques for pavement rehabilitation and highlights the need for reliable adhesion performance evaluation based on different spray amounts and surface conditions. Additionally, to evaluate the effect of the adhesion performance based on the spraying amount, a tensile adhesion test was conducted by applying spray amounts of 0.30, 0.45, and 0.60 l/m2 on different surface conditions. The basic and adhesion performances of the polymer-modified tack coat material are evaluated through direct tensile and shear bond strength tests. The test outcomes demonstrated that the newly developed polymer-modified tack coat material had considerably greater adhesion strength compared to the traditional rapid-setting products. Its adhesive strength was 1.68 times higher on concrete and 1.78 times higher on asphalt. The new trackless tack coat material exhibited an adhesion performance of 1.05 MPa in direct tensile strength at 0.45 l/m2, which was 1.21 times higher than the rapid-setting tack coat. Results also confirmed that the new tack coat material exhibits values 1.90 times greater than the conventional rapid-setting tack coat material in shear bond strength, respectively. By simulating the process of separation and re-adhesion of pavement layers caused, the new tack coat material shows a tensile adhesion strength of 63% of the original state, which is advantageous for securing the durability of the pavement. Overall, the newly developed polymer-modified trackless tack coat has been shown to effectively enhance the adhesion performance between pavement layers without process delay, highlighting the potential of the new tack coat material to enhance the durability of asphalt concrete overlay pavement on old cement concrete pavement.