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Objective: To analyze the burden of cardiovascular disease (CVD) attributed to low physical activity (LPA) and its changing trends in China from 1990 to 2019. Methods: On the basis of the province results of the Study of Global Burden of Disease 2019 in China, we described the distribution of CVD death and disability-adjusted life year (DALY) attributed to LPA by sex, age and province. Joinpoint 4.9.1.0 was used to calculate the average annual percentage change. Results: In 2019, the number of CVD deaths and DALY attributed to LPA in people aged ≥25 years were 0.127 million and 1.863 million person-years in China, respectively, The age-standardized mortality rate (ASMR) and standardized DALY rate of CVD attributed to LPA were slightly higher in men than in women, and much higher in ischemic heart disease patients than in ischemic stroke patients. The ASMR (8.85/100 000) and the standardized DALY rate (112.34/100 000) of CVD attributed to LPA in China in 2019 showed no obvious change compared with 1990, while decreased in the last decade. The largest increases in the mortality rate and DALY rate were observed in people aged ≥75 years from 1990 to 2019 (26.89%, 15.61%), but the mortality rate and DALY rate in people aged 60-74 years showed a decreasing trend. The mortality rate and DALY rate in men aged 25- 44 years showed the largest increases (37.50%, 35.49%), while women aged ≥75 years had the largest increases (31.00%, 18.02%). In 2019, the highest ASMR and standardized DALY rate of CVD attributed to LPA were found in Jilin, Inner Mongolia and Hebei. The largest increases were found in Qinghai (182.41%, 154.70%), Gansu (181.29%, 152.77%), and Chongqing (132.01%, 102.79%) and the largest decreases were found in Beijing (59.11%, 62.09%), Macau (41.89%, 39.37%) and Guangdong (36.93%, 40.72%) from 1990 to 2019. Conclusion: The disease burden of CVD attributed to LPA in China was quite high and showed gender, age and area specific differences.
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Doenças Cardiovasculares , Isquemia Miocárdica , Masculino , Humanos , Feminino , Doenças Cardiovasculares/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , China/epidemiologia , Pequim , Efeitos Psicossociais da DoençaRESUMO
Objective: To study the risk factors of adverse pregnancy outcomes for the diagnosis and treatment of pregnancy after cesarean section complicated with placenta previa. Methods: A national multicenter retrospective study was conducted to select a total of 747 pregnant women with the third trimester singleton pregnancy after cesarean section complicated with placenta previa from 12 tertiary hospitals in January 1st to December 31st, 2018. The risk factors of severe adverse outcomes [hysterectomy, intraoperative blood loss ≥1 000 ml, intraoperative diagnosis of placenta accreta spectrum disorders (PAS)] in pregnant women with second pregnancy complicated with placenta previa after cesarean section were investigated by logistic regression analysis. The roles of prenatal ultrasonography and magnetic resonance imaging (MRI) in the prediction of PAS and severe adverse outcomes were observed. According to whether vascular intervention was performed (uterine artery embolization or abdominal aortic balloon occlusion), the pregnant women were divided into the blocked group and the unblocked group, and the maternal and infant perinatal outcomes between the two groups were compared. Results: (1) General information: the hysterectomy rate of 747 pregnant women with second pregnancy complicated with placenta previa after cesarean section was 10.4% (78/747), the intraoperative blood loss ≥1 000 ml in 55.8% (417/747), and PAS was confirmed in 47.5% (355/747). The incidence of uterine rupture was 0.8% (6/747). (2) Analysis of risk factors for severe adverse outcomes: based on binary unconditioned logistic regression univariate and multivariate analysis, the risk factors for hysterectomy were the mode of vascular embolization and intraoperative blood loss. The probability of hysterectomy with uterine artery embolization was 5.319 times higher than that with abdominal aortic balloon occlusion (95%CI: 1.346-21.018). The risk factors of intraoperative blood loss ≥1 000 ml were the number of cesarean section delivery, ultrasonography indicated PAS and suspected PAS, intraoperative PAS and complete placenta previa. The risk factors for intraoperative PAS were uterine scar thickness, ultrasonography indicated PAS and suspected PAS, MRI indicated PAS and suspected PAS, and complete placenta previa. (3) The roles of ultrasonography and MRI in predicting PAS: the sensitivity and specificity of ultrasonography in predicting PAS were 47.5% and 88.4%; the kappa value was 0.279 (P<0.001), with fair agreement. The sensitivity and specificity of MRI to predict PAS were 79.2% and 97.8%, respectively. The kappa value was 0.702 (P<0.001), indicating a good agreement. The intraoperative blood loss and hysterectomy rate of pregnant women with PAS indicated by ultrasonography and MRI were significantly higher than those with PAS only by ultrasonography or MRI. (4) Influence of vascular occlusion on pregnancy outcome: there were no significant differences in intraoperative blood loss and incidence of intraoperative bleeding ≥1 000 ml between the blocked group and the unblocked group (all P>0.05). There was no significant difference in intraoperative blood loss between the pregnant women with abdominal aortic balloon occlusion, uterine artery embolization and those without occlusion (P=0.409). The hysterectomy rate of pregnant women with uterine artery embolization was significantly higher than those with abdominal aortic balloon occlusion [39.3% (22/56) vs 10.0% (5/50), P=0.001]. Conclusions: In the third trimester of pregnancy with placenta previa after cesarean section, MRI examination has better consistency in predicting PAS than ultrasonography examination. Ultrasonography examination combined with MRI examination could effectively predict the hysterectomy rate and intraoperative blood loss. Vascular occlusion could not reduce the amount of intraoperative blood loss. The hysterectomy rate of pregnant women with uterine artery embolization is higher than those with abdominal aortic balloon occlusion.
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Placenta Acreta , Placenta Prévia , Gravidez , Lactente , Feminino , Humanos , Cesárea , Placenta Acreta/cirurgia , Placenta Prévia/cirurgia , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Gestantes , Fatores de RiscoRESUMO
Objective: To develop a venous thromboembolism (VTE) risk assessment scale for adult burn patients and to test its reliability and validity. Methods: The scale research method and multi-center cross-sectional survey method were used. Based on the results of literature analysis method and brain-storming method, the letter questionnaire for experts was formulated. Then 27 experts (9 doctors of burn department, 9 vascular surgeons, and 9 nurses) were performed with two rounds of correspondences by Delphi method, and the reliability of the experts was analyzed. The weight of each item was determined by optimal sequence diagram method and expert importance evaluation to form the VTE Risk Assessment Scale for Adult Burn Patients. A total of 223 adult burn inpatients, who were admitted to 5 tier â ¢ grade A general hospitals including the Affiliated Hospital of Southwest Medical University, West China Hospital of Sichuan University, the Affiliated Hospital of North Sichuan Medical College, Nanchong Central Hospital, and the Second People's Hospital of Yibin City from October 1st 2019 to January 1st 2020, were selected as respondents by convenience sampling method. The first assessment was performed with the VTE Risk Assessment Scale for Adult Burn Patients within 24 hours of admission of patients, and real-time assessment was performed as the patients' condition and treatment changed. The highest value was taken as the result. Correlation coefficient method and critical ratio method were used for item analysis; Cronbach's α coefficient was used to test the internal consistency of scale; content validity index was used to analyze the content validity of the scale, and receiver's operating characteristic (ROC) curve was drawn to test the predictive validity of the scale. Data were statistically analyzed with chi-square test, Pearson correlation analysis, independent sample t test, and Z test. Results: As four questionnaires in the first round of correspondence were rejected as unqualified, and another 4 experts were selected for the 2 rounds of correspondence. Most of them were aged 41 to 50 years with postgraduate degrees, engaging in the current profession for 11 to 30 years, and all of them had professional titles of associate senior or above. The scale, constructed through literature analysis, group brainstorming, and two rounds of correspondence, includes 3 primary items and 50 secondary items. In the first round of correspondence, the recovery rate of valid questionnaires and the ratio with expert opinions were 85.2% (23/27) and 47.8% (11/23), respectively. In the second round of correspondence, the recovery rate of valid questionnaires and the ratio with expert opinions were 100% (27/27) and 11.1% (3/27), respectively. The average collective authority coefficients of experts were both 0.90 in the 2 rounds of correspondence. The mean values of importance assignment, full score rate, and selection rate above 4 were 4.21, 52.5%, and 77.2%, respectively, in the first round of correspondence, and 4.28, 45.2%, and 85.8%, respectively, in the second round of correspondence. The mean coefficients of variation and the mean value of Kendall's coefficient of harmony for each item were 0.21 and 0.30 in the first round of correspondence, respectively, and 0.16 and 0.36 in the second round of correspondence, respectively. In the first and second rounds of correspondence, the Kendall's coefficients of harmony of 3 primary items (age and underlying diseases, burn injury factors, and burn treatment factors) and total secondary items were statistically significant (with χ2 values of 121.46, 107.09, 116.00, 331.97, 169.97, 152.12, 141.54, and 471.70, P<0.01). The weights of primary items for age and underlying diseases, burn injury factors, and burn treatment factors were 0.04, 0.05, and 0.07, respectively. The weights of secondary items ranged from 0.71 to 0.99, with assigned values of 3 to 6. The total burn area of 223 patients ranged from 1% to 89% total body surface area, and the patients were aged from 19 to 96 years, with the risk assessment score from 0 to 98. Nine patients developed VTE, with a risk assessment score of 41 to 90. The scores of 37 items were significantly positively correlated with the total score of scale (with r values of 0.14 to 0.61, P<0.05 or P<0.01), and the items were retained. There were 36 secondary items with statistically significant differences between the patients in high-score group and low-score group (with Z values of -4.88 to -2.09, t values of -11.63 to -2.09, P<0.05 or P<0.01), and the items were retained. The total Cronbach's α coefficient of scale was 0.88. The total content validity index of scale was 0.95. The optimal threshold of the scale for the diagnosis of VTE was 40, at which the sensitivity was 88.9%, the specificity was 87.4%, the Youden index was 0.87, and the area under the ROC curve was 0.96 (with 95% confidence interval of 0.93 to 0.99, P<0.01). Conclusions: The age and underlying diseases, burn injury factors, and burn treatment factors are the risk factors for VTE in adult burn patients. The VTE risk assessment scale for adult burn patients developed based on these factors has good reliability and validity, and provide good reference value for clinical VTE risk assessment.
Assuntos
Queimaduras , Tromboembolia Venosa , Adulto , Queimaduras/complicações , Estudos Transversais , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Tromboembolia Venosa/diagnósticoRESUMO
Objective: To understand the capacity building needs on social organizations providing HIV prevention and treatment services for female sex workers (FSW). Methods: Questionnaires and interview were conducted with the heads of social organizations participating in China AIDS Fund for Non-Governmental Organizations (CAFNGO) project 2017-2018. Data from the CAFNGO's information system were compiled and analyzed using Excel 2016 and SPSS 25.0 software. The distribution of social organizations, availability of funds, and social organizations' needs for capacity building were analyzed. Results: Nationwide, 184 social organizations were involved in project '2017-2018 CAFNGO's FSW field work'. Out of which, 156 answers were valid. Social organizations that participated in the implementation of fund projects were mainly concentrated in the western region, accounting for 44.0% (81/184), with Sichuan, Guangxi, and Yunnan being the majority. However, the eastern part received the most financial support. Social organizations expressed the highest demand for project data collection and analysis, accounting for 68.6% (107/156). Items on risk analysis, response, and quality control project ranked the second, accounting for 64.1% (100/156). Results showed that statistically significant differences were seen on capacity building needs among social organization leaders with different levels of training on management of planning and finance of the project (χ2=5.78,P=0.016;χ2=8.99,P=0.003). Conclusions: Currently, the number of social organizations and the related fund provision concerning HIV prevention and control among FSWs were not consistent in China. Thus, it is necessary to encourage, guide, and support the development of social organizations and satisfy social organizations' needs on capacity-building and planning.
Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Profissionais do Sexo , Fortalecimento Institucional , China , Feminino , Infecções por HIV/prevenção & controle , HumanosRESUMO
Objective: The quick sequential organ failure assessment (qSOFA) score has been proposed as part of diagnostic criteria for sepsis, but there might be an underestimation of the incidence of qSOFA-negative sepsis according to a few recent studies. The purpose of this study was to evaluate the value of Oxford acute severity of illness score (OASIS) in identifying qSOFA-negative (qSOFA<2) patients with sepsis. Methods: Sepsis patients with negative qSOFA scores were selected from the Medical Information Mart for Intensive Care â ¢(MIMIC-â ¢), a database comprising de-identified health-related data from patients staying in the critical care units of Beth Israel Deaconess Medical Center between 2001 and 2012. Non-infectious patients with both qSOFA and SOFA scores less than 2 were enrolled as controls. Propensity score matching (PSM) analysis was used to reduce the effects of selection bias. Receiver operating characteristic (ROC) curve analysis was performed to assess the value of OASIS in discriminating qSOFA-negative patients with sepsis and to determine its optimal cut-off. Associations of OASIS with 28-day mortality after intensive care unit (ICU) admission, ICU mortality, and hospital mortality were further examined using multivariate Cox regression and multivariate logistic regression analysis. Results: 2 273 qSOFA-negative patients with sepsis and 3 342 non-sepsis controls were included finally with a PSM cohort consisted of 1 677 sepsis patients and 1 677 controls. Results of ROC analysis showed that the area under ROC curve was 0.753 [95% confidence interval (CI) 0.741-0.765] and the optimal OASIS threshold according to the Youden index was 26.5 and yielded a 67.2% sensitivity and 70.8% specificity. Multivariate regression analysis indicated that OASIS>26 was an independent risk factor for 28-day mortality (hazard ratio 2.80, 95% CI 2.15-3.65, P<0.01), ICU mortality (odds ratio 4.69, 95% CI 2.60-8.49, P<0.01), and hospital mortality (odds ratio 4.48, 95% CI 3.13-6.42, P<0.01). Analysis of the PSM cohort presented consistent results. Conclusions: OASIS had a good discriminative value to differentiate qSOFA-negative patients with sepsis from those without sepsis.
Assuntos
Escores de Disfunção Orgânica , Sepse , Mortalidade Hospitalar , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: In Canada, government insurance covers eye care services provided by ophthalmologists and other physicians. However, government coverage for services provided by optometrists, non-medical school trained primary eye care providers, varies regionally. Little is known about the impact of a funding model in which ophthalmologist services are government-insured but services provided by optometrists are not, on eye care utilization and eye disease detection and treatment. We aimed to address this question by examining geographic variations in eye care service utilization on Prince Edward Island (PEI). METHODS: PEI physician-billing data from 2010 to 2012 was analyzed across five distinct geographic regions (Charlottetown, Summerside, Prince, Queens & Kings and Stratford). The residential location of patients and practice locations of eye care providers were identified using the first three digits of their respective postal code. Age-standardized rates were computed for comparisons across different regions. RESULTS: There were six ophthalmologists practicing on PEI, five with offices in Charlottetown. Twenty optometrists practiced on the island with offices across the province. Stratford is closest and Prince farthest from Charlottetown. Age-standardized utilization rates of ophthalmologists per 100 populations were 10.44 in Charlottetown and 10.90 in Stratford, which was significantly higher than in other regions (7.74-8.92; p < 0.05). The disparities were most pronounced amongst the elderly. The prevalence of glaucoma visits was higher in Charlottetown (6.10%) and Stratford (6.38%) and lower in other regions. A similar pattern was observed for the prevalence of cataract visits. While the prevalence of diabetes visits was higher in Prince and Summerside, the utilization of ophthalmologists by people with diabetes was almost twice as high in Charlottetown (6.49%) than in Prince (3.88%). CONCLUSIONS: The observed discrepancies in vision care utilization across geographic regions were likely attributed to barriers in accessing government-insured, geographically concentrated ophthalmologists, as opposed to a reflection of the true differences in eye disease occurrence. The lower prevalence of glaucoma visits in regions farther away from ophthalmologist offices may result in delayed detection and blindness in this population. Encouraging ophthalmologists to work in other areas of the province and/or to publicly fund services provided by optometrists may mitigate the observed disparities. TRIAL REGISTRATION: Not applicable.
Assuntos
Catarata/diagnóstico , Glaucoma/diagnóstico , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Oftalmologia , Optometria , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Idoso , Catarata/terapia , Estudos Transversais , Feminino , Glaucoma/terapia , Pessoal de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Cobertura do Seguro , Masculino , Pessoa de Meia-Idade , Oftalmologia/organização & administração , Optometria/organização & administração , Ilha do Príncipe EduardoRESUMO
The declining number of physician scientists is an alarming issue. A systematic review of all existing programs described in the literature was performed, so as to highlight which programs may serve as the best models for the training of successful physician scientists. Multiple databases were searched, and 1,294 articles related to physician scientist training were identified. Preference was given to studies that looked at number of confirmed publications and/or research grants as primary outcomes. Thirteen programs were identified in nine studies. Eighty-three percent of Medical Scientist Training Program (MSTP) graduates, 77% of Clinician Investigator Training Program (CI) graduates, and only 16% of Medical Fellows Program graduates entered a career in academics. Seventy-eight percent of MSTP graduates succeeded in obtaining National Institute of Health (NIH) grants, while only 15% of Mayo Clinic National Research Service Award-T32 graduates obtained NIH grants. MSTP physician scientists who graduated in 1990 had 13.5 ± 12.5 publications, while MSTP physician scientists who graduated in 1975 had 51.2 ± 38.3 publications. Additionally, graduates from the Mayo Clinic's MD-PhD Program, the CI Program, and the NSRA Program had 18.2 ± 20.1, 26.5 ± 24.5, and 17.9 ± 26.3 publications, respectively. MSTP is a successful model for the training of physician scientists in the United States, but training at the postgraduate level also shows promising outcomes. An increase in the number of positions available for training at the postgraduate level should be considered.
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Pesquisa Biomédica/educação , Pesquisa Biomédica/estatística & dados numéricos , Médicos , Docentes de Medicina/estatística & dados numéricos , Humanos , Internato e Residência/organização & administração , Internato e Residência/estatística & dados numéricos , Grupos Minoritários/estatística & dados numéricos , Apoio à Pesquisa como Assunto/estatística & dados numéricos , Distribuição por Sexo , Estados UnidosRESUMO
This study aimed to investigate the curative effect and costs of surgical and gamma knife treatments on intractable epilepsy caused by temporal-hippocampal sclerosis. The subjects comprised patients who suffered from intractable epilepsy caused by temporal-hippocampal sclerosis and received treatment in the Department of Neurosurgery of our hospital between 2010 and 2011. After obtaining their consent, patients were evaluated and selected to receive surgical or gamma knife treatments. In the surgical group, the short-term curative rate was 92.60% and the average cost was US$ 1311.50 while in the gamma knife group, the short-term curative rate was 53.79%, and the average cost was US$ 2786.90. Both surgical and gamma knife treatments of intractable epilepsy caused by temporal-hippocampal sclerosis are safe and effective, but the short-term curative effect of surgical treatment is better than that of gamma knife, and its cost is lower.
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Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/patologia , Radiocirurgia/economia , Adulto , Análise Custo-Benefício , Epilepsia Resistente a Medicamentos/economia , Epilepsia Resistente a Medicamentos/patologia , Epilepsia do Lobo Temporal/economia , Epilepsia do Lobo Temporal/patologia , Feminino , Humanos , Masculino , Radiocirurgia/métodos , Esclerose , Resultado do TratamentoRESUMO
Immunoelectron microscopy is wrought with technical limitations that complicate its use. However, advances in correlative light and electron microscopy have recently lead to improvements in this field. We report the development of a semi-correlative approach to investigate the ultrastructural location of an antiphospholipid antibody within the syncytiotrophoblast. This method offers several advantages over existing methodologies, since it preserves antigenicity, shows good immunolabel penetrability and does not require specialized equipment. The use of a pre-embedding screen has also allowed us to target individual placental villi and overcome sampling limitations of the electron microscope. This simple, cost-effective method is likely to find widespread application in placental research.
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Microscopia Eletrônica/métodos , Microscopia Imunoeletrônica/métodos , Proteínas da Gravidez/metabolismo , Trofoblastos/química , Animais , Anticorpos Antifosfolipídeos/análise , Feminino , Humanos , GravidezRESUMO
To quickly obtain information about airborne infectious disease transmission in enclosed environments is critical in reducing the infection risk to the occupants. This study developed a combined computational fluid dynamics (CFD) and Markov chain method for quickly predicting transient particle transport in enclosed environments. The method first calculated a transition probability matrix using CFD simulations. Next, the Markov chain technique was applied to calculate the transient particle concentration distributions. This investigation used three cases, particle transport in an isothermal clean room, an office with an underfloor air distribution system, and the first-class cabin of an MD-82 airliner, to validate the combined CFD and Markov chain method. The general trends of the particle concentrations vs. time predicted by the Markov chain method agreed with the CFD simulations for these cases. The proposed Markov chain method can provide faster-than-real-time information about particle transport in enclosed environments. Furthermore, for a fixed airflow field, when the source location is changed, the Markov chain method can be used to avoid recalculation of the particle transport equation and thus reduce computing costs.
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Microbiologia do Ar , Doenças Transmissíveis/transmissão , Surtos de Doenças/prevenção & controle , Material Particulado , Simulação por Computador , Humanos , Hidrodinâmica , Cadeias de MarkovRESUMO
This research presented an evaluation for the ecological quality status (EcoQS) of three semi-enclosed coastal areas using fuzzy integrated assessment method (FIAM). With this method, the hierarchy structure was clarified by an index system of 11 indicators selected from biotic elements and physicochemical elements, and the weight vector of index system was calculated with Delphi-Analytic Hierarchy Process (AHP) procedure. Then, the FIAM was used to achieve an EcoQS assessment. As a result of assessment, most of the sampling stations demonstrated a clear gradient in EcoQS, ranging from high to poor status. Among the four statuses, high and good, owning a ratio of 55.9% and 26.5%, respectively, were two dominant statuses for three bays, especially for Sansha Bay and Luoyuan Bay. The assessment results were found consistent with the pressure information and parameters obtained at most stations. In addition, the sources of uncertainty in classification of EcoQS were also discussed.
Assuntos
Baías/química , Monitoramento Ambiental/métodos , Poluição da Água/estatística & dados numéricos , Biodiversidade , China , Clorofila/análise , Clorofila A , Ecossistema , Lógica Fuzzy , Oceanos e Mares , Fitoplâncton/classificação , Fitoplâncton/crescimento & desenvolvimentoRESUMO
PURPOSE: Recent clinical trials and animal studies have indicated that the tissue sensitivity to radiation induced lung injury (RILI) may be region- specific. In this study, we propose a new 4D cone beam CT (CBCT) basedcompliance imaging method to measure regional pulmonary function change in precisely irradiated small animal under CBCT guidance on small animal radiation research platform (SARRP) to facilitate our understanding of region-specific tissue sensitivity to RILI. METHODS: Four Sprague-Dawley rats underwent prospective pressure gated 4D CBCT on SARRP. Three animals were selected as control group which underwent a second 4D CBCT scan. The fourth animal was irradiated in the central lung (24 Gy) using 3 × 3 mm collimating cone 2 months prior to the scan. The specific compliance (Csp) was calculated via the real time pressure measurement from the ventilator and displacement field from 3D B-spline image registration between the end of inhale and end of exhale phases from the 4D CBCT scan. The 3D Csp maps from the control animal group were mapped to the irradiated animal as a Csp functional atlas for statistical analysis. We alsoevaluated the repeatability of the Csp measurement on a voxel-by-voxel basis. RESULTS: No significant Csp difference is found after two month of radiation between the irradiated rat (0.22±0.05) and the functional atlas (0.21±0.07). The observation is consistent with previous publications. The averaged linear correlation coefficient between the voxel-by-voxel Csp measurements from initial and repeat scans in control group is 0.98. CONCLUSIONS: We proposed a method that uses 4D CBCT based compliance imaging to measure region-specific tissue sensitivity of RILI. We compared the irradiated animal two months after radiation with the control group. Our study shows an excellent robustness of the proposed method for regional lung tissue specific compliance measurement. This work was supported in part by UVa George Amorino Pilot Grant.
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AKT1 controls important processes in medial temporal lobe (MTL) development and plasticity, but the impact of human genetic variation in AKT1 on these processes is not known in healthy or disease states. Here, we report that an AKT1 variant (rs1130233) previously associated with AKT1 protein expression, prefrontal function and schizophrenia, affects human MTL structure and memory function. Further, supporting AKT1's role in transducing hippocampal neuroplasticity and dopaminergic processes, we found epistasis with functional polymorphisms in BDNF and COMT--genes also implicated in MTL biology related to AKT1. Consistent with prior predictions that these biologic processes relate to schizophrenia, we found epistasis between the same AKT1, BDNF and COMT functional variants on schizophrenia risk, and pharmacogenetic interactions of AKT1 with the effects on cognition and brain volume measures by AKT1 activators in common clinical use--lithium and sodium valproate. Our findings suggest that AKT1 affects risk for schizophrenia and accompanying cognitive deficits, at least in part through specific genetic interactions related to brain neuroplasticity and development, and that these AKT1 effects may be pharmacologically modulated in patients.
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Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas c-akt/genética , Esquizofrenia/genética , Esquizofrenia/patologia , Lobo Temporal/patologia , Antipsicóticos/uso terapêutico , Mapeamento Encefálico , Fator Neurotrófico Derivado do Encéfalo/genética , Catecol O-Metiltransferase/genética , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Farmacoeconomia , Epistasia Genética/efeitos dos fármacos , Epistasia Genética/genética , Feminino , Estudos de Associação Genética , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/genética , Testes Neuropsicológicos , Oxigênio/sangue , Estimulação Luminosa , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/genética , Esquizofrenia/complicações , Esquizofrenia/tratamento farmacológico , Lobo Temporal/irrigação sanguínea , Lobo Temporal/efeitos dos fármacosRESUMO
PURPOSE: Original TomoTherapy systems may involve a trade-off between conformity and treatment speed, the user being limited to three slice widths (1.0, 2.5, and 5.0 cm). This could be overcome by allowing the jaws to define arbitrary fields, including very small slice widths (<1 cm), which are challenging for a beam model. The aim of this work was to incorporate the dynamic jaws feature into a Monte Carlo (MC) model called TomoPen, based on the MC code PENELOPE, previously validated for the original TomoTherapy system. METHODS: To keep the general structure of TomoPen and its efficiency, the simulation strategy introduces several techniques: (1) weight modifiers to account for any jaw settings using only the 5 cm phase-space file; (2) a simplified MC based model called FastStatic to compute the modifiers faster than pure MC; (3) actual simulation of dynamic jaws. Weight modifiers computed with both FastStatic and pure MC were compared. Dynamic jaws simulations were compared with the convolution∕superposition (C∕S) of TomoTherapy in the "cheese" phantom for a plan with two targets longitudinally separated by a gap of 3 cm. Optimization was performed in two modes: asymmetric jaws-constant couch speed ("running start stop," RSS) and symmetric jaws-variable couch speed ("symmetric running start stop," SRSS). Measurements with EDR2 films were also performed for RSS for the formal validation of TomoPen with dynamic jaws. RESULTS: Weight modifiers computed with FastStatic were equivalent to pure MC within statistical uncertainties (0.5% for three standard deviations). Excellent agreement was achieved between TomoPen and C∕S for both asymmetric jaw opening∕constant couch speed and symmetric jaw opening∕variable couch speed, with deviations well within 2%∕2 mm. For RSS procedure, agreement between C∕S and measurements was within 2%∕2 mm for 95% of the points and 3%∕3 mm for 98% of the points, where dose is greater than 30% of the prescription dose (gamma analysis). Dose profiles acquired in transverse and longitudinal directions through the center of the phantom were also compared with excellent agreement (2%∕2 mm) between all modalities. CONCLUSIONS: The combination of weights modifiers and interpolation allowed implementing efficiently dynamic jaws and dynamic couch features into TomoPen at a minimal cost in terms of efficiency (simulation around 8 h on a single CPU).
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Método de Monte Carlo , Radioterapia Assistida por Computador/métodos , Estudos de Viabilidade , Reprodutibilidade dos TestesRESUMO
This study aimed to assess insight in Chinese schizophrenia patients and to identify its relationship with socio-demographic and clinical factors, executive functions and quality of life (QOL). A cohort of 139 clinically stable schizophrenia patients was selected by consecutively screening patients diagnosed with schizophrenia who were attending the outpatient department of a university-affiliated psychiatric hospital in China. Participants' socio-demographic and clinical characteristics, including psychotic symptoms, depression and insight, as well as QOL and executive functions, were periodically assessed with standardized rating instruments. Patients received standard psychiatric care and were followed up for 1 year. Impaired insight was found to be common in stable Chinese schizophrenia patients (76.3%), with merely 5% showing improvement over the 1-year follow-up. Insight was inversely correlated with positive and negative symptoms at all but the 12-month assessment and with both the physical and mental components of QOL at baseline and the 12-month assessment. Insight was not associated with depressive symptoms or executive functions. Standard psychiatric care does not improve the level of insight in clinically stable Chinese schizophrenia outpatients, which warrants the introduction of specific therapeutic interventions that enhance insight.
Assuntos
Psicologia do Esquizofrênico , Adulto , Conscientização , China , Função Executiva , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Qualidade de Vida/psicologia , Ajustamento Social , Fatores SocioeconômicosRESUMO
This study assessed the performance of Sequential Organ Failure Assessment, Logistic Organ Dysfunction Score and Multiple Organ Dysfunction Score in outcome prediction in severe sepsis. A total of 528 consecutive patients with a diagnosis of severe sepsis were enrolled from two surgical intensive care units of university hospitals in China. Clinical and laboratory data of patients were collected and admission and maximum values of each scoring system were calculated. Areas under the receiver operating characteristic curve, which were used to assess discrimination, were 0.80, 0.83 and 0.74 for admission Sequential Organ Failure Assessment, Logistic Organ Dysfunction Score and Multiple Organ Dysfunction Score respectively, and 0.91, 0.93 and 0.86 for corresponding maximum values respectively. Calibration assessed by the Hosmer-Lemeshow statistic was better with admission (chi2 = 18.2) and maximum Logistic Organ Dysfunction Score (chi2 = 19.6) than with admission (chi2 = 98.1) and maximum Multiple Organ Dysfunction Score (chi2 = 30.9). Brier Scores, indicating the overall performance of the scores, were 0.18, 0.17 and 0.22 for admission Sequential Organ Failure Assessment, Logistic Organ Dysfunction Score and Multiple Organ Dysfunction Score respectively, and 0.12, 0.10 and 0.15 for their maximum counterparts respectively. This study found good performance of both admission Sequential Organ Failure Assessment and Logistic Organ Dysfunction Score in severe sepsis, and a slightly weaker performance of admission Multiple Organ Dysfunction Score. Since poor calibration was observed in Logistic Organ Dysfunction Score and Multiple Organ Dysfunction Score, we suggest further study of customisation of these scores in critical illness with severe sepsis.
Assuntos
Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/epidemiologia , Sepse/epidemiologia , China , Comorbidade , Estado Terminal , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de DoençaRESUMO
The 2009 Viral Clearance Symposium (Indianapolis, IN, USA) was held to interactively discuss methods for virus removal and inactivation during biopharmaceutical manufacture. Its origin was the result of worldwide regulatory and industry recognition that challenges, gaps, and opportunities for improvement exist, which if formally addressed could benefit the field as a whole. The symposium began with presentations by the FDA (USA) and the Paul Ehrlich Institute (PEI, Germany), which highlighted viral clearance study information reported in regulatory submissions. In these two presentations, and a subsequent series of brief industry presentations covering various unit operations, it was made clear that many unit operations are quite effective in clearing viruses. This was particularly true of low pH inactivation, anion exchange chromatography, and virus filtration. Moreover, the follow-up discussions at the end of each session, and the wrap-up at the end of the symposium, aimed to synthesize the regulatory data mining knowledge base with the industry-generated data. The symposium also revealed a number of unknowns in the field which were defined and prioritized, and served as potential action items for future experimental studies.
Assuntos
Vírus/isolamento & purificação , Animais , Biotecnologia , Cromatografia/métodos , Cromatografia por Troca Iônica , Detergentes/farmacologia , Contaminação de Medicamentos/prevenção & controle , Indústria Farmacêutica , Filtração/métodos , Humanos , Concentração de Íons de Hidrogênio , Proteína Estafilocócica A , Estados Unidos , United States Food and Drug Administration , Inativação de Vírus/efeitos dos fármacosRESUMO
It was recently noticed that in vitro motility assays, driven by random distributed dynein c, microtubules could form self-organized circular patterns, which could be of importance to the design of nanobiomechanical machines. In order to determine key parameters that control the self-organized movement of microtubules, a phenomenological modeling study taking account of the microtubule joining probability distribution and microtubule bias was conducted to investigate the self-organization of microtubules driven by dynein motors.