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1.
J Thorac Imaging ; Publish Ahead of Print2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33399350

RESUMO

Photon-counting computed tomography (CT) is a developing technology that has the potential to address some limitations of CT imaging and bring about improvements and potentially new applications to this field. Photon-counting detectors have a fundamentally different detection mechanism from conventional CT energy-integrating detectors that can improve dose efficiency, spatial resolution, and energy-discrimination capabilities. In the past decade, promising human studies have been reported in the literature that have demonstrated benefits of this relatively new technology for various clinical applications. In this review, we provide a succinct description of the photon-counting detector technology and its detection mechanism in comparison with energy-integrating detectors in a manner understandable for clinicians and radiologists, introduce benefits and some of the existing challenges present in this technology, and provide an overview of the current status and potential clinical applications of this technology in imaging of the thorax by providing example images acquired with an investigational whole-body photon-counting CT scanner.

2.
J Exp Med ; 218(2)2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33180929

RESUMO

Typhoid Vi vaccines have been shown to be efficacious in children living in endemic regions; however, a widely accepted correlate of protection remains to be established. We applied a systems serology approach to identify Vi-specific serological correlates of protection using samples obtained from participants enrolled in an experimental controlled human infection study. Participants were vaccinated with Vi-tetanus toxoid conjugate (Vi-TT) or unconjugated Vi-polysaccharide (Vi-PS) vaccines and were subsequently challenged with Salmonella Typhi bacteria. Multivariate analyses identified distinct protective signatures for Vi-TT and Vi-PS vaccines in addition to shared features that predicted protection across both groups. Vi IgA quantity and avidity correlated with protection from S. Typhi infection, whereas higher fold increases in Vi IgG responses were associated with reduced disease severity. Targeted antibody-mediated functional responses, particularly neutrophil phagocytosis, were also identified as important components of the protective signature. These humoral markers could be used to evaluate and develop efficacious Vi-conjugate vaccines and assist with accelerating vaccine availability to typhoid-endemic regions.


Assuntos
Febre Tifoide/imunologia , Vacinas Tíficas-Paratíficas/imunologia , Vacinas Conjugadas/imunologia , Adulto , Carga Bacteriana , Humanos , Imunidade Humoral , Imunogenicidade da Vacina , Imunoglobulina G/sangue , Fatores de Tempo , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/farmacologia , Vacinas Conjugadas/farmacologia
3.
Am J Med Genet A ; 185(1): 15-25, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33029936

RESUMO

Biallelic mutations in SNORD118, encoding the small nucleolar RNA U8, cause leukoencephalopathy with calcifications and cysts (LCC). Given the difficulty in interpreting the functional consequences of variants in nonprotein encoding genes, and the high allelic polymorphism across SNORD118 in controls, we set out to provide a description of the molecular pathology and clinical spectrum observed in a cohort of patients with LCC. We identified 64 affected individuals from 56 families. Age at presentation varied from 3 weeks to 67 years, with disease onset after age 40 years in eight patients. Ten patients had died. We recorded 44 distinct, likely pathogenic, variants in SNORD118. Fifty two of 56 probands were compound heterozygotes, with parental consanguinity reported in only three families. Forty nine of 56 probands were either heterozygous (46) or homozygous (three) for a mutation involving one of seven nucleotides that facilitate a novel intramolecular interaction between the 5' end and 3' extension of precursor-U8. There was no obvious genotype-phenotype correlation to explain the marked variability in age at onset. Complementing recently published functional analyses in a zebrafish model, these data suggest that LCC most often occurs due to combinatorial severe and milder mutations, with the latter mostly affecting 3' end processing of precursor-U8.

4.
J Cell Mol Med ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33295687

RESUMO

The metabolic syndrome (MetS) is an escalating problem worldwide, causing left ventricular stiffening, an early characteristic of diastolic dysfunction for which no treatment exists. As diastolic dysfunction and stiffening in MetS patients are associated with increased circulating dipeptidyl peptidase-4 (DPP-4) levels, we investigated whether the clinically approved DPP-4 inhibitor linagliptin reduces left ventricular stiffness in MetS-induced cardiac disease. Sixteen-week-old obese ZSF1 rats, displaying the MetS and left ventricular stiffness, received linagliptin-supplemented or placebo diet for four weeks. Linagliptin significantly reduced obesity, hyperlipidaemia, and hyperglycaemia and improved left ventricular relaxation. This improved relaxation was related to decreased cardiac fibrosis and cardiomyocyte passive stiffness (Fpassive ). The reduced Fpassive was the result of titin isoform switching from the stiff N2B to the more flexible N2BA and increased phosphorylation of total titin and specifically its N2Bus region (S4080 and S3391). Importantly, DPP-4 directly cleaved titin in vitro, resulting in an increased Fpassive , which was prevented by simultaneous administration of linagliptin. In conclusion, linagliptin improves left ventricular stiffness in obese ZSF1 rats by preventing direct DPP4-mediated titin cleavage, as well as by modulating both titin isoform levels and phosphorylation. Reducing left ventricular stiffness by administering linagliptin might prevent MetS-induced early diastolic dysfunction in human.

5.
J Sch Health ; 90(12): 976-984, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33184884

RESUMO

BACKGROUND: The benefits of youth engagement are well documented. In this paper, we examine youth engagement in America's Promise Alliance's Every School Healthy initiative, a part of the Robert Wood Johnson Foundation's Together for Healthy and Successful Schools Initiative (THSS). METHODS: Six community acceleration sites were selected through a competitive grant-making process. Sites were required to describe youth engagement strategies. A case study design was employed to examine how sites conceptualize youth engagement as well as youth engagement strategies employed across 6 sites. Data sources included observations, team member debriefs, and document review. RESULTS: There was variation in how youth engagement and youth voice are conceptualized in educational settings, and readiness for youth engagement. Sites actively solicited and implemented youth engagement resources and strategies. CONCLUSIONS: By failing to engage young people, well-intentioned adults miss important opportunities. Youth engagement presents an exciting opportunity for school leaders, policymakers, and program planners to gain a deeper understanding of the factors that influence individual and community health and wellbeing and, in turn, helps them to develop responsive policies and programs.

6.
J Sch Health ; 90(12): 995-1003, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33184888

RESUMO

BACKGROUND: Whole school, whole community, whole child (WSCC) approaches to education address contexts beyond school that influence young people's academic and life outcomes. These recommended approaches demand mobilization of an array of actors, but such mobilization is challenging. Little research has explored strategies for convening national experts to support local communities. METHODS: This paper presents a case narrative of Every School Healthy (ESH), a grant-funded effort to support organizations/school districts in 6 communities building WSCC initiatives by engaging national youth development organizations as expert advisors to ESH and communities. A thematic analysis of the narrative yielded 3 key learnings. RESULTS: Three themes emerged as key learnings regarding implementation of national-local initiatives: (1) baseline assessment of local communities should be conducted to identify opportunities for maximizing strengths; (2) national organizations must be flexible with the expertise they bring to the initiative; (3) national organizations should prioritize community-cultivated solutions and meet communities where they are. CONCLUSIONS: The 3 themes presented in this case narrative offer insights for effectively mobilizing national organizations to support healthy, equitable school environments at the local level.

7.
J Org Chem ; 85(23): 15660-15666, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33226802

RESUMO

In a recent methodological study investigating the synthesis of N-alkoxyazomethine ylides, an unexpected aminal byproduct was generated during our attempt to isolate O-benzyl-N-((trimethylsilyl)methyl)hydroxylamine. After a strategic investigation, silica gel was discovered to be the cause of the byproduct formation. Through the mechanistic insight from control and trapping experiments, we propose the formation of a methaniminium ion via a novel aza-Peterson reaction, which ultimately triggers a sequential iminium ion cascade sequence. Herein, we discuss the elucidation of this cascade reaction mechanism and the constraints for the byproduct formation.

8.
Sci Total Environ ; : 143323, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33213912

RESUMO

Over 50% of new refuse truck sales have been compressed natural gas (CNG). Compared to diesel, CNG is less expensive on diesel gallon equivalent (dge) basis. This study quantifies the real-world fuel use and tailpipe exhaust emissions from three front- and three side-loader refuse trucks, each with a spark ignition CNG engine, three-way catalyst, and similar gross weight. Measurements were made at 1 Hz using a portable emissions measurement system (PEMS). Inter-cycle and inter-vehicle variability is quantified. Effect of vehicle weight was analyzed and comparisons were made with MOVES predicted cycle average emission rates. In total, about 220,000 s of data covering 490 miles of operation were recorded. The average fuel economy was 1.9 miles per dge. On average the trucks spent 53% of time in idle, which includes trash collection activity. The average speeds were 10 mph and 5 mph, for front- and side-loader trucks, respectively. Overall, compared to side-loader trucks, front-loader trucks had 55% better fuel economy and 60% lower emission rates. Compared to diesel trucks, CNG truck cycle average NOx and PM emission rates, at 1.2 g/mile and 0.006 g/mile respectively, were substantially lower while CO and HC rates, at 29 g/mile and 6 g/mile respectively, were considerably higher. Fuel use and CO2 emissions rates increased by 10% due to increase in truck weight during trash collection, while CO emissions rates increased by up to 30%. Compared to measured values, MOVES estimated cycle average fuel use and CO2 emissions were 25% lower, CO emissions are 70% lower, and NOx emissions were 200% higher. Results from this study can be used to improve solid waste life cycle and tailpipe emission factor models and, when combined with previous studies on diesel refuse trucks, evaluate the effect on fuel use and emissions from adoption of CNG refuse trucks.

9.
BMJ ; 371: m4087, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148535

RESUMO

OBJECTIVE: To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Published studies in Medline from 1 January 2000 to 10 April 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. RESULTS: The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. CONCLUSIONS: Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.


Assuntos
Neoplasias/mortalidade , Neoplasias/terapia , Tempo para o Tratamento , Humanos , Fatores de Risco , Análise de Sobrevida
10.
PLoS Negl Trop Dis ; 14(10): e0008783, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33079959

RESUMO

Enteric fever is a systemic infection caused by Salmonella Typhi or Paratyphi A. In many endemic areas, these serovars co-circulate and can cause multiple infection-episodes in childhood. Prior exposure is thought to confer partial, but incomplete, protection against subsequent attacks of enteric fever. Empirical data to support this hypothesis are limited, and there are few studies describing the occurrence of heterologous-protection between these closely related serovars. We performed a challenge-re-challenge study using a controlled human infection model (CHIM) to investigate the extent of infection-derived immunity to Salmonella Typhi or Paratyphi A infection. We recruited healthy volunteers into two groups: naïve volunteers with no prior exposure to Salmonella Typhi/Paratyphi A and volunteers previously-exposed to Salmonella Typhi or Paratyphi A in earlier CHIM studies. Within each group, participants were randomised 1:1 to oral challenge with either Salmonella Typhi (104 CFU) or Paratyphi A (103 CFU). The primary objective was to compare the attack rate between naïve and previously challenged individuals, defined as the proportion of participants per group meeting the diagnostic criteria of temperature of ≥38°C persisting for ≥12 hours and/or S. Typhi/Paratyphi bacteraemia up to day 14 post challenge. The attack-rate in participants who underwent homologous re-challenge with Salmonella Typhi was reduced compared with challenged naïve controls, although this reduction was not statistically significant (12/27[44%] vs. 12/19[63%]; Relative risk 0.70; 95% CI 0.41-1.21; p = 0.24). Homologous re-challenge with Salmonella Paratyphi A also resulted in a lower attack-rate than was seen in challenged naïve controls (3/12[25%] vs. 10/18[56%]; RR0.45; 95% CI 0.16-1.30; p = 0.14). Evidence of protection was supported by a post hoc analysis in which previous exposure was associated with an approximately 36% and 57% reduced risk of typhoid or paratyphoid disease respectively on re-challenge. Individuals who did not develop enteric fever on primary exposure were significantly more likely to be protected on re-challenge, compared with individuals who developed disease on primary exposure. Heterologous re-challenge with Salmonella Typhi or Salmonella Paratyphi A was not associated with a reduced attack rate following challenge. Within the context of the model, prior exposure was not associated with reduced disease severity, altered microbiological profile or boosting of humoral immune responses. We conclude that prior Salmonella Typhi and Paratyphi A exposure may confer partial but incomplete protection against subsequent infection, but with a comparable clinical and microbiological phenotype. There is no demonstrable cross-protection between these serovars, consistent with the co-circulation of Salmonella Typhi and Paratyphi A. Collectively, these data are consistent with surveillance and modelling studies that indicate multiple infections can occur in high transmission settings, supporting the need for vaccines to reduce the burden of disease in childhood and achieve disease control. Trial registration NCT02192008; clinicaltrials.gov.

12.
Sci Rep ; 10(1): 15701, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973263

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.


Assuntos
Anestésicos/administração & dosagem , Diástole/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Isoflurano/administração & dosagem , Ketamina/administração & dosagem , Xilazina/administração & dosagem , Animais , Diástole/fisiologia , Ecocardiografia , Frequência Cardíaca/fisiologia , Masculino , Obesidade/fisiopatologia , Ratos , Disfunção Ventricular Esquerda/fisiopatologia
13.
PET Clin ; 15(4): 463-475, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32888545

RESUMO

Total-body PET scans will initiate a new era for the PET clinic. The benefits of 40-fold effective sensitivity improvement provide new capabilities to image with lower radiation dose, perform delayed imaging, and achieve improved temporal resolution. These technical features are detailed in the first of this 2-part series. In this part, the clinical impacts of the novel features of total-body PET scans are further explored. Applications of total-body PET scans focus on the real-time interrogation of systemic disease manifestations in a variety of practical clinical contexts. Total-body PET scans make clinical systems biology imaging a reality.

14.
Cardiol Young ; 30(12): 1783-1787, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32951625

RESUMO

OBJECTIVE: Infective endocarditis remains a severe complication associated with a high morbidity and mortality in patients after heart valve replacement. Exploration of the pathogenesis is of high demand and we, therefore, present a competent model that allows studying bacterial adherence and the role of plasma fibrinogen in this process using a new in-house designed low-volume flow chamber. Three cardiac graft tissues used for pulmonary valve replacement have been tested under shear conditions to investigate the impact of surface composition on the adhesion events. METHODS: Tissue pieces of cryopreserved homograft (non-decellularised), decellularised homograft and bovine pericardium patch were investigated for fibrinogen binding. Adherence of Staphylococcus aureus to these graft tissues was studied quantitatively under flow conditions in our newly fabricated chamber based on a parallel plates' modality. The method of counting colony-forming units was reliable and reproducible to assess the propensity of different graft materials for bacterial attachment under shear. RESULTS: Bacterial perfusions over all plasma-precoated tissues identified cryopreserved homograft with the lowest affinity for S. aureus compared to decellularised homograft presenting a significantly higher bacterial adhesion (p < 0.05), which was linked to a more avid fibrinogen binding (p < 0.01). Bovine pericardial patch, as a reference tissue in this study, was confirmed to be the most susceptible tissue graft for the bacterial adhesion, which was in line with our previous work. CONCLUSION: The two studied homograft tissues showed different levels of bacterial attachment, which might be postulated by the involvement of fibrinogen in the adhesion mechanism(s) shown previously for bovine tissues.

15.
Lancet Oncol ; 21(8): 1089-1098, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32758463

RESUMO

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, causing more than 300 000 deaths globally each year. In addition to screening and prevention, effective cancer treatment is needed to reduce cervical cancer mortality. We discuss the role of imaging in cervical cancer management and estimate the potential survival effect of scaling up imaging in several different contexts. METHODS: Using a previously developed microsimulation model of global cancer survival, we estimated stage-specific cervical cancer 5-year net survival in 200 countries and territories. We evaluated the potential survival effect of scaling up treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), and imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single photon emission CT [SPECT]) to the mean level of high-income countries, both individually and in combination. FINDINGS: We estimate global cervical cancer 5-year net survival as 42·1% (95% uncertainty interval [UI] 33·8-48·5). Among individual imaging modalities, expanding MRI would yield the largest 5-year survival gains globally (data are absolute percentage point increase in survival 0·6, 95% UI 0·1-2·1), scaling up ultrasound would yield the largest gains in low-income countries (0·5, 0·0-3·7), expanding CT and x-ray would have the greatest effect in Latin America (0·8, 0·0-3·4) and Oceania (0·4, 0·0-3·2), and expanding PET would yield the largest gains in high-income countries (0·2, 0·0-0·8). Scaling up SPECT did not show major changes in any region. Among individual treatment modalities, scaling up radiotherapy would yield the largest absolute percentage point gains in low-income countries (5·2, 0·3-13·5), and expanding surgery would have the largest effect in lower-middle-income countries (7·4, 0·3-21·1) and upper-middle-income countries (0·8, 0·0-2·9). Estimated survival gains in high-income countries were very modest. However, the gains from expanding any single treatment or imaging modality individually were small across all income levels and geographical settings. Scaling up all treatment modalities could improve global 5-year net survival to 52·4% (95% UI 44·6-62·0). In addition to expanding treatment, improving quality of care could raise survival to 57·5% (51·2-63·5), and the cumulative effect of scaling up all imaging modalities together with expanded treatment and quality of care could improve 5-year net survival for cervical cancer to 62·5% (57·7-67·8). INTERPRETATION: Comprehensive scale-up of treatment, imaging, and quality of care could substantially improve global cervical cancer 5-year net survival, with quality of care and imaging improvements each contributing about 25% of the total potential gains. These findings suggest that a narrow focus on the availability of treatment modalities could forgo substantial survival gains. Investments in imaging equipment, personnel, and quality of care efforts will also be needed to successfully scale up cervical cancer treatment worldwide. FUNDING: Harvard T H Chan School of Public Health and National Cancer Institute.


Assuntos
Saúde Global/estatística & dados numéricos , Análise de Sobrevida , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia , Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Feminino , Humanos , Modelos Estatísticos
16.
J Plast Reconstr Aesthet Surg ; 73(12): 2111-2120, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32747182

RESUMO

BACKGROUND: Prominent ears are the most common congenital abnormality of the head and neck, occurring in 5% of the Caucasian population. Facial disfigurement can cause psychosocial distress, low self-esteem and varying levels of social isolation most notable in school-age children. Although prominent ear correction is the most frequently performed aesthetic operation in children and adolescents, to our knowledge, the relationship between prominent ears and psychological, social and educational issues has not been systematically assessed. PURPOSE OF STUDY: To investigate the psychological, social and educational impact of prominent ears and to examine how prominent ear correction affects health-related quality of life (HRQoL). METHODS: A systematic review was conducted using a protocol registered with PROSPERO and in line with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses statement. A comprehensive search of the literature was conducted using MEDLINE, EMBASE, PyscINFO, HMIC Health Management Information Consortium, Ovid Journals Database, NHS Wales Full-Text Journals and The Cochrane Database. The inclusion criteria stated that any study investigating the association between psychological, social or educational issues, or HRQoL and prominent ears or otoplasty should be incorporated. All studies were reviewed by two authors, with data extracted for the studies finally included. FINDINGS: Fourteen articles were finally included, with a total of 786 patients. Thirteen out of 14 papers analysed the post-operative effect of surgical correction of prominent ears. The most common motivating factor for surgery was bullying, with young males of school age being the worst affected. Prominent ear patients report higher levels of bullying and social problems, and lower levels of physical activity than patients with more severe facial disfigurements. Every study that assessed the psychosocial impact of surgery on prominent ears found a significant benefit to HRQoL. CONCLUSION AND RELEVANCE: Prominent ears pose severe psychological and social issues that should not be underestimated. Surgical correction has consistently been shown to significantly improve HRQoL.


Assuntos
Orelha Externa/cirurgia , Escolaridade , Procedimentos Cirúrgicos Otológicos/psicologia , Autoimagem , Ajustamento Social , Isolamento Social , Adolescente , Bullying , Criança , Orelha Externa/anormalidades , Humanos
17.
Nat Commun ; 11(1): 4080, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796848

RESUMO

Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Artificial intelligence (AI) has the potential to aid in rapid evaluation of CT scans for differentiation of COVID-19 findings from other clinical entities. Here we show that a series of deep learning algorithms, trained in a diverse multinational cohort of 1280 patients to localize parietal pleura/lung parenchyma followed by classification of COVID-19 pneumonia, can achieve up to 90.8% accuracy, with 84% sensitivity and 93% specificity, as evaluated in an independent test set (not included in training and validation) of 1337 patients. Normal controls included chest CTs from oncology, emergency, and pneumonia-related indications. The false positive rate in 140 patients with laboratory confirmed other (non COVID-19) pneumonias was 10%. AI-based algorithms can readily identify CT scans with COVID-19 associated pneumonia, as well as distinguish non-COVID related pneumonias with high specificity in diverse patient populations.


Assuntos
Inteligência Artificial , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Betacoronavirus/isolamento & purificação , Criança , Pré-Escolar , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Aprendizado Profundo , Feminino , Humanos , Imageamento Tridimensional/métodos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto Jovem
18.
PLoS Comput Biol ; 16(8): e1007874, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822340

RESUMO

Shear stress induces directed endothelial cell (EC) migration in blood vessels leading to vessel diameter increase and induction of vascular maturation. Other factors, such as EC elongation and interaction between ECs and non-vascular areas are also important. Computational models have previously been used to study collective cell migration. These models can be used to predict EC migration and its effect on vascular remodelling during embryogenesis. We combined live time-lapse imaging of the remodelling vasculature of the quail embryo yolk sac with flow quantification using a combination of micro-Particle Image Velocimetry and computational fluid dynamics. We then used the flow and remodelling data to inform a model of EC migration during remodelling. To obtain the relation between shear stress and velocity in vitro for EC cells, we developed a flow chamber to assess how confluent sheets of ECs migrate in response to shear stress. Using these data as an input, we developed a multiphase, self-propelled particles (SPP) model where individual agents are driven to migrate based on the level of shear stress while maintaining appropriate spatial relationship to nearby agents. These agents elongate, interact with each other, and with avascular agents at each time-step of the model. We compared predicted vascular shape to real vascular shape after 4 hours from our time-lapse movies and performed sensitivity analysis on the various model parameters. Our model shows that shear stress has the largest effect on the remodelling process. Importantly, however, elongation played an especially important part in remodelling. This model provides a powerful tool to study the input of different biological processes on remodelling.


Assuntos
Hidrodinâmica , Remodelação Vascular , Animais , Circulação Sanguínea , Movimento Celular/fisiologia , Forma Celular , Biologia Computacional , Células Endoteliais/fisiologia , Codorniz/anatomia & histologia , Codorniz/embriologia , Estresse Mecânico
19.
Acad Radiol ; 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32855051

RESUMO

RATIONALE AND OBJECTIVES: The purpose of this study was to investigate the potential of photon-counting CT (PCCT) to improve quantitative image quality for low dose imaging compared to energy-integrating detector CT (EID CT). MATERIALS AND METHODS: An investigational scanner (Siemens, Germany) with PCCT and EID CT subsystems was used to compare image quality performance at four dose levels: 1.7, 2, 4, 6 mGy CTDIvol, all at or below current dose values used for conventional abdominal CT. A CT quality control phantom with a homogeneous section for noise measurements and a section with cylindrical inserts of air (-910 HU), polystyrene (50 HU), acrylic (205 HU), and Teflon (1000 HU) was imaged and characterized in terms of noise, resolution, contrast-to-noise ratio (CNR), and detectability index. A second phantom with a 30 cm diameter was also imaged containing iodine solutions ranging from 0.125 to 8 mg I/mL. CNR of the iodine vials was computed as a function of CT dose and iodine concentration. RESULTS: With resolution unaffected by dose in both PCCT and EID CT, PCCT images exhibited 22.1-24.0% improvement in noise across dose levels evaluated. This noise improvement translated into a 29-41% improvement in CNR and 20-36% improvement in detectability index. For iodine contrast, PCCT images had a higher CNR for all combinations of iodine contrast and dose evaluated. CONCLUSION: For the conditions studied, PCCT exhibited superior image quality compared to EID CT. For iodine detection, PCCT offered a notable advantage with improved CNR at all doses and iodine concentration levels.

20.
Proc Natl Acad Sci U S A ; 117(36): 22281-22292, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32843340

RESUMO

Seawater Mg:Ca and Sr:Ca ratios are biogeochemical parameters reflecting the Earth-ocean-atmosphere dynamic exchange of elements. The ratios' dependence on the environment and organisms' biology facilitates their application in marine sciences. Here, we present a measured single-laboratory dataset, combined with previous data, to test the assumption of limited seawater Mg:Ca and Sr:Ca variability across marine environments globally. High variability was found in open-ocean upwelling and polar regions, shelves/neritic and river-influenced areas, where seawater Mg:Ca and Sr:Ca ratios range from ∼4.40 to 6.40 mmol:mol and ∼6.95 to 9.80 mmol:mol, respectively. Open-ocean seawater Mg:Ca is semiconservative (∼4.90 to 5.30 mol:mol), while Sr:Ca is more variable and nonconservative (∼7.70 to 8.80 mmol:mol); both ratios are nonconservative in coastal seas. Further, the Ca, Mg, and Sr elemental fluxes are connected to large total alkalinity deviations from International Association for the Physical Sciences of the Oceans (IAPSO) standard values. Because there is significant modern seawater Mg:Ca and Sr:Ca ratios variability across marine environments we cannot absolutely assume that fossil archives using taxa-specific proxies reflect true global seawater chemistry but rather taxa- and process-specific ecosystem variations, reflecting regional conditions. This variability could reconcile secular seawater Mg:Ca and Sr:Ca ratio reconstructions using different taxa and techniques by assuming an error of 1 to 1.50 mol:mol, and 1 to 1.90 mmol:mol, respectively. The modern ratios' variability is similar to the reconstructed rise over 20 Ma (Neogene Period), nurturing the question of seminonconservative behavior of Ca, Mg, and Sr over modern Earth geological history with an overlooked environmental effect.

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