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Disease may be both a cause and consequence of stress, and physiological responses to infectious disease may involve stress coping mechanisms that have important fitness consequences. For example, glucocorticoid and glycemic responses may affect host fitness by altering resource allocation and use in hosts, and these responses may be affected by competing stressors. To better understand the factors that affect host responses to infection, we challenged the immune system of field acclimatized pygmy rattlesnakes, Sistrurus miliarius, with a sterile antigen, lipopolysaccharide (LPS), and measured the glucocorticoid and glycemic response in healthy non-reproductive snakes, snakes afflicted with an emerging mycosis (ophidiomycosis), and pregnant snakes. We hypothesized that LPS challenge would result in a glucocorticoid and glycemic response typical of the vertebrate acute phase response (APR), and therefore predicted that LPS challenge would result in an acute increase in plasma corticosterone (CORT) and a decline in plasma glucose in all individuals. Additionally, we hypothesized that the APR would be attenuated in individuals simultaneously coping with additional challenges to homeostasis (i.e., disease or reproduction). As predicted, immune challenge elicited an acute increase in plasma CORT and a decrease in plasma glucose. Snakes coping with ophidiomycosis and pregnant snakes were able to mount a robust glucocorticoid and hypoglycemic response to LPS challenge, which was contrary to our hypothesis. Our findings clarify directions of causality linking infection, glucocorticoids, and glucose, and emphasize the importance of future research examining the fitness consequences of interactions between stress and disease in wildlife threatened by emerging pathogens.
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Layered metal thio- and selenophosphates (MTPs) are a family of van der Waals gapped materials that exhibit a multitude of functionalities in terms of magnetic, ferroelectric, and optical properties. Despite the recent progress in terms of understanding the material properties of these compounds, the potential of MTPs as a material class yet needs further scrutiny, especially in terms of nonlinear optical properties. Recent reports of efficient low-order harmonic generation and extremely high third-order nonlinear optical properties in MTPs suggest the potential application of these materials in integrated nanophotonics. In this article, we investigate the high-order nonlinear response of bulk and exfoliated thin-film crystals of copper indium thiophosphate (CIPS) to intense mid-infrared fields through experimental and computational studies of high-order harmonic generation (HHG). From a driving laser source with a 3.2 µm wavelength, we generate odd and even harmonics up to the 10th order, exceeding the bandgap of the material. We note conversion efficiencies as high as 10-7 measured for the fifth and seventh harmonics and observe that the harmonic intensities follow a power law scaling with the driving laser intensity, suggesting a perturbative nonlinear optical origin of the observed harmonics for both bulk and thin flakes. Furthermore, first-principles calculations suggest that the generation of the highest harmonic orders results from electron-electron interactions, suggesting a correlation-mediated enhancement of the high-order optical nonlinearity.
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INTRODUCTION: In 1948, the indirect ophthalmoscope revealed full intra-ocular retinoblastoma, documented on paper with coloured pencils. At SickKids, eCancerCareRB (eCCRB) digital drawings and timeline have facilitated patient care, education, and research. METHODS: Each child's eCCRB timeline shows treatments and dates. The SwimmerRB tool presents eCCRB data for research with time "0" start of intervention. Any tumour treatment after the intervention indicates recurrence; no cancer treatments indicate complete response. To further quantify the impact of retinoblastoma on child/family, we arbitrarily assigned a "consequence" score to each standard treatment (i.e., focalâ¯=â¯1, intra-arterial chemotherapyâ¯=â¯3, enucleation last eyeâ¯=â¯30). Retrospective control eCCRB patients were matched to study participants by similar "propensity" scores before time "0." Postintervention scores indicated effectiveness. RESULTS: eCCRB included 700 patients with retinoblastoma treated between 2001 and 2023 at SickKids. SwimmerRB facilitated comparing eCCRB patients treated with single- versus triple-drug intra-arterial chemotherapy. In the phase 1 Chemoplaque Clinical Trial, SwimmerRB analysis compared number of treatments before and after the Chemoplaque. Consequence scores quantitating negative outcomes will be refined by quality-of-life studies including those with lived experience. DEPICT HEALTH (DEPICT) on the cloud-hosted technology will soon replace eCCRB (now-outdated technology), offering digital retinoblastoma care to the world. DISCUSSION: eCCRB (only in SickKids) is the time-tested prototype for DEPICT on the cloud. DEPICT brings digital retinal drawings, timeline, research, and clinical consultation to full view for families as partners in retinoblastoma care. DEPICT will be offered through the International Retinoblastoma Consortium to any site caring for children with retinoblastoma.
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OBJECTIVES: Implementation of an interprofessional program at Princess Margaret Cancer Centre, including nurse-led proactive calls to support patients with gynecologic cancers with malignant bowel obstruction, demonstrated improved outcomes compared with historical controls. The aim of the study was to convert the proactive calls into an electronic monitoring program to assess it's feasibility and scalability in patients with gynecologic cancers with or at risk of malignant bowel obstruction. METHODS: 'My Bowels on Track' smartphone application included weekly/biweekly electronic patient-reported outcomes (PROs), educational materials, and a secure messaging system. Based on PRO answers, an alerting system flagged patients with symptoms or uncompleted PROs. Nurses tracked and called patients on receiving clinical or compliance alerts. The primary objective was to assess adherence (≥70% PRO completion per patient considered an adherent patient) in the first 2 months on the program. A secondary objective was to assess the positive predictive value (PPV) of the alerts to trigger recommendations. RESULTS: Forty patients were enrolled between August 2021 and September 2022. Median age was 64.5 years (range 29-79 years). Primary diagnosis was ovarian (75%), endometrial (17.5%), or cervical (7.5%) cancer, and 92.5% of patients were receiving systemic therapy. Median duration on the program was 55 days (range 8-121 days). The 2-month adherence was 65% (95% CI 50% to 80%) and the overall adherence was 60% (95% CI 43% to 75%). Sixty-five symptom-related alerts (75% severe, 25% moderate) were reported in 60% (24/40) of patients. There were 59 recommendations triggered by the alerts. The PPV of the alerts to trigger actions was 72% (95% CI 58% to 82%). CONCLUSIONS: This pilot electronic malignant bowel obstruction monitoring program with real-time PRO assessment was feasible, and 65% of participants were adherent during the first 2 months on the program. The PRO response-based alerting system flagged concerning symptoms in 60% of participants, with a PPV of 72% to trigger nurse-led actions and/or management recommendations. TRIAL REGISTRATION NUMBER: NCT03260647.
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Neoplasias dos Genitais Femininos , Obstrução Intestinal , Aplicativos Móveis , Smartphone , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos de Viabilidade , Neoplasias dos Genitais Femininos/complicações , Obstrução Intestinal/etiologia , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/terapia , Medidas de Resultados Relatados pelo PacienteRESUMO
Few-cycle, long-wavelength sources for generating isolated attosecond soft x ray pulses typically rely upon complex laser architectures. Here, we demonstrate a comparatively simple setup for generating sub-two-cycle pulses in the short-wave infrared based on multidimensional solitary states in an N2O-filled hollow-core fiber and a two-channel light-field synthesizer. Due to the temporal phase imprinted by the rotational nonlinearity of the molecular gas, the redshifted (from 1.03 to 1.36 µm central wavelength) supercontinuum pulses generated from a Yb-doped laser amplifier are compressed from 280 to 7 fs using only bulk materials for dispersion compensation.
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PURPOSE: The use of virtual care rapidly increased during the COVID-19 pandemic and has persisted as a routine method of care delivery. Much of the literature on virtual care in oncology has focused on solid tumors, and little is known about its application in malignant hematology. METHODS: We performed a retrospective review of patients with hematologic malignancies at Princess Margaret Cancer Centre from October 2019 to March 2021 to determine the use of virtual care during this period, cost-savings associated with virtual visits, and patient satisfaction. Patient satisfaction was assessed using the Your Voice Matters survey, a provincially administered survey to evaluate patient experience. RESULTS: Overall, 12.1% (1,122/9,295) of patients had a virtual visit during the study period (0% from October 2019 to February 2020, 36% from March to August 2020, and 30% from September 2020 to March 2021), of which 36% were in the lymphoma clinic and 46% were in the myeloma clinic. The mean two-way opportunity cost for an in-person visit was $168.00 CAD per person with public transit, and $120.40 CAD per person driving. Responses to the Your Voice Matters survey indicated that patients with a virtual visit reported that physical symptoms were discussed appropriately (mean 4.73/5), and were more likely to ask for a follow-up virtual visit compared with patients with in-person visits (mean 4.50/5 v 3.02/5, respectively; P < .01). CONCLUSION: These findings suggest that virtual care may be a feasible and well-received tool for delivering care to a substantial proportion of patients with hematologic malignancies, while enabling substantial cost-savings to patients.
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COVID-19 , Neoplasias Hematológicas , Mieloma Múltiplo , Humanos , COVID-19/epidemiologia , Pandemias , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Instituições de Assistência Ambulatorial , Mieloma Múltiplo/complicações , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapiaRESUMO
The Mekong River Delta in Vietnam, is concerned by numerous microplastic-related issues such as a lack of wastewater treatment facilities and mismanagement of plastic waste released from agriculture, aquaculture and related activities. This study aimed to examine the presence of microplastics in surface water and sediment by collecting samples from six sites along the Tien River and its distributaries in February 2019. The results showed that the average concentration of microplastics over the entire area was 53.8 ± 140.7 items m-3 in surface water and 6.0 ± 2.0 items g-1 dried weight in sediment, with a predominance of microplastic fibres rather than fragments, respectively 85 % and 98 % in surface water and sediment. In the main flow of surface water, the concentration of microplastics was stable; however, in the sediment, microplastic concentration was affected by the high dynamic flow regime rather than the sources where microplastics are released.
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Microplásticos , Poluentes Químicos da Água , Plásticos , Rios , Água , Vietnã , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodosRESUMO
OBJECTIVES: Hypopharyngeal and laryngeal cancers are aggressive and usually diagnosed at advanced stage with esophagus invasion. Total pharyngolaryngoesophagectomy with gastric pull-up reconstruction has been a common surgery for these cancers but long-term outcomes are still questionable. This study aimed to investigate short-term and long-term outcomes of patients who underwent this surgery. METHODS: Patients with hypopharyngeal or laryngeal cancer invading cervical esophagus who underwent total pharyngolaryngoesphagectomy with gastric pull-up between 2012 and 2016 was included and followed up until 2021. Short-term outcomes were complications and long-term outcomes were overall survival (OS) and disease-free survival (DFS). RESULTS: Fifty patients were included with a mean age of 60.3 years and 94% were male. Pyriform fossa was the most common primary site of tumor (50%), followed by posterior hypopharyngeal wall (18%) and postcricoid region (18%). Mean operating time, postoperative oral intake and hospital stay was 363.1 ± 43.6 minutes, 8.8 ± 3.6 days and 14.2 ± 3.0 days respectively. Complications occurred in 15 patients (30%) without any in-hospital death. During the follow-up period, 17 patients had recurrence and 35 patients died. Median (95% confidence interval [CI]) OS and DFS time were 30 (21-37) and 30 (19-36) months. Five-year OS and DFS probability (95% CI) were 22.6% (12.8-39.7) and 22.7% (12.9-39.8). CONCLUSIONS: Total pharyngolaryngoesophagectomy with gastric pull-up is feasible and safe. However, even with curative surgery and multimodal treatment, advanced pharyngeal or laryngeal cancer with cervical esophagus invasion still has poor survival outcome.
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Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Laríngeas/cirurgia , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/patologia , Mortalidade Hospitalar , Esôfago/cirurgia , Hipofaringe/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Virtual care (VC) visits (telephone or video) and email-based patient communication have been rapidly adopted to facilitate cancer care during the COVID-19 pandemic. Inequities in access and patient experience may arise as these digital health tools become prevalent. OBJECTIVE: We aimed to characterize inequities in access and patient-reported experience following adoption of digital health tools at a tertiary cancer center during the COVID-19 pandemic. METHODS: We designed a cross-sectional study of outpatients with visits from September to December 2020. Patient characteristics and responses to an email-based patient-experience survey were collated. Inequities in access were assessed across three pairs of comparison groups: (1) patients with VC and in-person visits, (2) patients with and without documented email addresses, and (3) responders and nonresponders to the survey. Inequities in patient-reported experience were assessed among survey responders. Demographics were mapped to area-level averages from national census data. Socioeconomic status was mapped to area-level dimensions of the Canadian Index of Multiple Deprivation. Covariate balance between comparison groups was assessed using standardized mean differences (SMDs), with SMD≥0.2 indicating differences between groups. Associations between patient experience satisfaction scores and covariates were assessed using multivariable analyses, with P<.05 indicating statistical significance. RESULTS: Among the 42,194 patients who had outpatient visits, 62.65% (n=26,435) had at least one VC visit and 31.15% (n=13,144) were emailable. Access to VC and email was similar across demographic and socioeconomic indices (SMD<0.2). Among emailable patients, 21.84% (2870/13,144) responded to the survey. Survey responsiveness was similar across indices, aside from a small difference by age (SMD=0.24). Among responders, 24.4% received VC and were similar to in-person responders across indices (SMD<0.2). VC and in-person responders had similar satisfaction levels with all care domains surveyed (all P>.05). Regardless of visit type, patients had variable satisfaction with care domains across demographic and socioeconomic indices. Patients with higher ethnocultural composition scores were less satisfied with the cultural appropriateness of their care (odds ratio [OR] 0.70, 95% CI 0.57-0.86). Patients with higher situational vulnerability scores were less satisfied with discussion of physical symptoms (OR 0.67, 95% CI 0.48-0.93). Patients with higher residential instability scores were less satisfied with discussion of both physical (OR 0.81, 95% CI 0.68-0.97) and emotional (OR 0.86, 95% CI 0.77-0.96) symptoms, and also with the duration of their visit (OR 0.85, 95% CI 0.74-0.98; P=.02). Male patients were more satisfied with how their health care provider had listened to them (OR 1.64, 95% CI 1.11-2.44; P=.01). CONCLUSIONS: Adoption of VC and email can equitably maintain access and patient-reported experience in cancer care across demographics and socioeconomic indices. Existing health inequities among structurally marginalized patients must continue to be addressed to improve their care experience.
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COVID-19 , Neoplasias , Telemedicina , Humanos , Masculino , COVID-19/epidemiologia , Pandemias , Estudos Transversais , Satisfação do Paciente , Canadá , Comunicação , Eletrônica , Neoplasias/terapiaRESUMO
Anthropogenic fibres are an emerging pollutant worldwide. The Can Gio mangrove area is located downstream of the Saigon River, and is characterised by high level of anthropogenic fibres originating from domestic and industrial textile and apparel manufacturing. In this area, biota is thus subjected to a high potential risk of anthropogenic fibre contamination. This study aims to characterise the accumulation of anthropogenic fibres in different tissues, i.e. gills, digestive systems, and remaining tissues, of white clams (Meretrix lyrata) cultivated in the Can Gio beach sand, during a seven-month sampling period. The results showed an average concentration of 3.6 ± 2.1 fibres individual-1 or 2.7 ± 2.4 fibres g-1 ww. Higher fibre accumulation was observed in remaining tissues than in gills and digestive systems, and no temporal variation was observed in all clam tissues. The intake of fibres by humans consuming clams was estimated to be 324 fibres inhabitant-1 yr-1.
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Bivalves , Animais , Cidades , Humanos , Rios , VietnãRESUMO
Few-cycle sources with high average powers are required for applications to attosecond science. Raman-enhanced spectral broadening of Yb-doped laser amplifiers in molecular gases can yield few-cycle pulses, but thermal excitation of vibrational and rotational degrees of freedom may preclude high-power operation. Here we investigate changes in the spectral broadening associated with repetitive laser interactions in an ${{\rm{N}}_2}{\rm{O}}$-filled hollow-core fiber. By comparing experimental measurements of the spectrum associated with each laser pulse to simulations based on a density matrix model, we find that losses in a spectral bandwidth and transmission are largely dominated by thermal excitation of the gas.
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The Red River Delta is considered one of the largest megadelta systems in Asia. The formation of this delta has been controlled by the continent-ocean interaction and sea-level fluctuation during the Cenozoic. In this study, we present a new sequence stratigraphic framework of the Red River Delta based on borehole lithofacies analysis and high resolution seismic data. The Late Pleistocene-Holocene sediments in the coastal zone of the Red River Delta were subdivided into three systems tracts: (1) the lowstand systems tract (LST) is characterized by a Late Pleistocene alluvial silty sand facies complex (arLSTQ1 3b); (2) the transgressive systems tract (TST) is illustrated by the coastal marsh facies complex and the lagoonal greenish-gray clay facies of Early-Middle Holocene (amt, mtTSTQ2 1-2); and (3) the highstand systems tract (HST) is composed of the Middle-Late Holocene deltaic clayish silt facies complex (amhHSTQ2 2-3). The boundaries between these three systems tracts are not isochronous, namely: (1) The LST-HST boundary has been associated with the Würm 2 Glaciation, which occurred at ~40-18 Ka.; (2) The TST-LST boundary is identified by a transgressive erosion surface, whose age ranges from ~12-5 Ka.; and (3) the HST-TST boundary is an unconformity between the submarine deltaic facies complex and the Middle Holocene marine flooding plain.
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Microplastics in atmospheric fallouts from a developing megacity influenced by a tropical monsoon climate were investigated during a year. Three sites were selected according to the surrounding population density, the land use and occupation. The microplastic deposition fluxes varied between of 71-917 items m-2 d-1, for an observation size range of 300-5000 µm. Fibers predominated while fragments were observed occasionally. Unexpectedly, contrary to available scientific literature, deposition fluxes did not vary temporally with rainfall and wind intensity or direction, showing no effect of the tropical climate. Variations were observed between sites and were attributed to their environmental characteristics: population density and occupation space. The median length of fibers also differed between sites and could be related to in-situ fragmentation processes due to occupation space (solid waste treatment facility). Those first results from tropical climate region are showing interesting insights and are opening new perspectives on the understanding of microplastics fate from atmospheric fallouts.
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Microplásticos , Poluentes Químicos da Água , Monitoramento Ambiental , Plásticos/análise , Clima Tropical , Poluentes Químicos da Água/análise , VentoRESUMO
Importance: The coronavirus disease 2019 (COVID-19) pandemic has burdened health care resources and disrupted care of patients with cancer. Virtual care (VC) represents a potential solution. However, few quantitative data support its rapid implementation and positive associations with service capacity and quality. Objective: To examine the outcomes of a cancer center-wide virtual care program in response to the COVID-19 pandemic. Design, Setting, and Participants: This cohort study applied a hospitalwide agile service design to map gaps and develop a customized digital solution to enable at-scale VC across a publicly funded comprehensive cancer center. Data were collected from a high-volume cancer center in Ontario, Canada, from March 23 to May 22, 2020. Main Outcomes and Measures: Outcome measures were care delivery volumes, quality of care, patient and practitioner experiences, and cost savings to patients. Results: The VC solution was developed and launched 12 days after the declaration of the COVID-19 pandemic. A total of 22â¯085 VC visits (mean, 514 visits per day) were conducted, comprising 68.4% (range, 18.8%-100%) of daily visits compared with 0.8% before launch (P < .001). Ambulatory clinic volumes recovered a month after deployment (3714-4091 patients per week), whereas chemotherapy and radiotherapy caseloads (1943-2461 patients per week) remained stable throughout. No changes in institutional or provincial quality-of-care indexes were observed. A total of 3791 surveys (3507 patients and 284 practitioners) were completed; 2207 patients (82%) and 92 practitioners (72%) indicated overall satisfaction with VC. The direct cost of this initiative was CAD$ 202â¯537, and displacement-related cost savings to patients totaled CAD$ 3â¯155â¯946. Conclusions and Relevance: These findings suggest that implementation of VC at scale at a high-volume cancer center may be feasible. An agile service design approach was able to preserve outpatient caseloads and maintain care quality, while rendering high patient and practitioner satisfaction. These findings may help guide the transformation of telemedicine in the post COVID-19 era.
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Assistência Ambulatorial/organização & administração , COVID-19 , Institutos de Câncer/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Oncologia/organização & administração , Telemedicina/organização & administração , Centros de Atenção Terciária/organização & administração , Assistência Ambulatorial/economia , Agendamento de Consultas , Atitude do Pessoal de Saúde , Institutos de Câncer/economia , Redução de Custos , Análise Custo-Benefício , Prestação Integrada de Cuidados de Saúde/economia , Estudos de Viabilidade , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Oncologia/economia , Ontário , Satisfação do Paciente , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Telemedicina/economia , Centros de Atenção Terciária/economia , Fatores de Tempo , Carga de TrabalhoRESUMO
In aquatic environments, assessment of microplastic concentrations is increasing worldwide but environments from developing countries remain under-evaluated. Due to disparities of facilities, financial resources and human resources between countries, protocols of sampling, analysis and observations used in developed countries cannot be fully adapted in developing ones, and required specific adaptations. In Viet Nam, an adapted methodology was developed and commonly adopted by local researchers to implement a microplastic monitoring in sediments and surface waters of 21 environments (rivers, lakes, bays, beaches) of eight cities or provinces. Microplastic concentrations in surface waters varied from 0.35 to 2522 items m-3, with the lowest concentrations recorded in the bays and the highest in the rivers. Fibers dominated over fragments in most environments (from 47% to 97%). The microplastic concentrations were related to the anthropogenic pressure on the environment, pointing out the necessity in a near future to identify the local sources of microplastics.
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Microplásticos , Poluentes Químicos da Água , Cidades , Monitoramento Ambiental , Sedimentos Geológicos , Humanos , Plásticos , Rios , Vietnã , Poluentes Químicos da Água/análiseRESUMO
The field of attosecond science was first enabled by nonlinear compression of intense laser pulses to a duration below two optical cycles. Twenty years later, creating such short pulses still requires state-of-the-art few-cycle laser amplifiers to most efficiently exploit "instantaneous" optical nonlinearities in noble gases for spectral broadening and parametric frequency conversion. Here, we show that nonlinear compression can be much more efficient when driven in molecular gases by pulses substantially longer than a few cycles because of enhanced optical nonlinearity associated with rotational alignment. We use 80-cycle pulses from an industrial-grade laser amplifier to simultaneously drive molecular alignment and supercontinuum generation in a gas-filled capillary, producing more than two octaves of coherent bandwidth and achieving >45-fold compression to a duration of 1.6 cycles. As the enhanced nonlinearity is linked to rotational motion, the dynamics can be exploited for long-wavelength frequency conversion and compressing picosecond lasers.
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Tuberculosis is an uncommon cause of chronic suppurative otitis media. Delay in diagnosis can lead to delayed treatment, resulting in significant complications. We describe a case of tuberculous otitis media with osteomyelitis of the craniofacial bones in a 44-year-old woman with chronic painless suppurative otorrhea, not responding to antibiotics, hearing loss, and facial palsy. Chest X-ray was normal. Computed tomography of the temporal bone showed the destruction of the left zygomatic bone, clivus, and petrous part of the temporal bone. Polymerase chain reaction was positive for Mycobacterium tuberculosis (MTB), and histopathological findings showed caseous necrotizing tissues. Sputum culture was negative for MTB. The patient was successfully treated with surgery and anti-tuberculosis drugs. The polymerase chain reaction is a sensitive, rapid diagnostic tool used to diagnose TB. Surgical approaches and operative biopsy should be considered when the cause of the chronic purulent discharge is still unknown.
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Osteomielite/diagnóstico , Otite Média Supurativa/diagnóstico por imagem , Otite Média Supurativa/microbiologia , Tuberculose/complicações , Adulto , Antituberculosos/uso terapêutico , Doença Crônica , Feminino , Humanos , Mycobacterium tuberculosis/genética , Osteomielite/microbiologia , Otite Média Supurativa/tratamento farmacológico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológicoRESUMO
Significant efforts are being made to develop artificial intelligence technologies for health settings. In a health system that has been notoriously slow to adopt innovative technologies, it is important to consider the implementation of a new technology early in the development stage, especially one that will have added challenges of trust and transparency. To facilitate this process, an implementation framework for artificial intelligence technologies in clinical settings has been created.
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Inteligência Artificial , Atenção à SaúdeRESUMO
A modular facile route has been developed to synthesize functionalized 2,5-di(thiophen-2-yl)-1-H-arylpyrroles from readily available starting materials. These units are compatible with various polymerization conditions and are versatile building blocks for conjugated polymers. The polymers show high thermal stability and solubility in a number of solvents. Characterization of the polymers reveals a correlation between molecular packing, controllable by polymer design, and charge carrier mobility.
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Tumor-associated macrophages (TAMs) are heterogeneous and can adopt a spectrum of activation states between pro-inflammatory and pro-tumorigenic in response to the microenvironment. We have previously shown that TTI-621, a soluble SIRPαFc fusion protein that blocks the CD47 "do-not-eat" signal, promotes tumor cell phagocytosis by IFN-γ-primed macrophages. To assess the impact of CD47 blockade on diverse types of macrophages that are found within the tumor microenvironment, six different polarized human macrophage subsets (M(-), M(IFN-γ), M(IFN-γ+LPS), M(IL-4), M(HAGG+IL-1ß), M(IL-10 + TGFß)) with distinct cell surface markers and cytokine profiles were generated. Blockade of CD47 using TTI-621 significantly increased phagocytosis of lymphoma cells by all macrophage subsets, with M(IFN-γ), M(IFN-γ+LPS) and M(IL-10 + TGFß) macrophages having the highest phagocytic response. TTI-621-mediated phagocytosis involves macrophage expression of both the low- and high-affinity Fcγ receptors II (CD32) and I (CD64), respectively. Moreover, macrophages with lower phagocytic capabilities (M(-), M(IL-4), M(HAGG+IL-1ß)) could readily be re-polarized into highly phagocytic macrophages using various cytokines or TLR agonists. In line with the in vitro study, we further demonstrate that TTI-621 can trigger phagocytosis of tumor cells by diverse subsets of isolated mouse TAMs ex vivo. These data suggest that TTI-621 may be efficacious in triggering the destruction of cancer cells by a diverse population of TAMs found in vivo and support possible combination approaches to augment the activity of CD47 blockade.