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PURPOSE: We evaluated the association between intravesical prostate protrusion (IPP) and the detection rate of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TB). MATERIALS AND METHODS: A total of 538 consecutive men who underwent MRI-TRUS fusion TB and concomitant systematic biopsy were evaluated. IPP on MRI was independently measured by 4 blinded reviewers. The primary outcome was per-lesion detection of csPCa on TB. We assessed the association between IPP and csPCa detection on TB, controlling for age, prostate specific antigen, Prostate Imaging Reporting and Data System® (PI-RADS®) score, prostate volume, targeted cores sampled and previous biopsy experience. RESULTS: A total of 847 PI-RADS 3 or greater lesions were targeted across 570 biopsies. Intra- and interrater reliability for measuring IPP was strong. A total of 81 (14.2%), 127 (22.3%), 237 (41.6%) and 125 (21.9%) men had 0, small, medium and large IPP, respectively. A total of 230, 392 and 196 lesions were PI-RADS 3, 4 and 5, respectively. Of the lesions 198 (34.7%) had csPCa on TB. The overall relationship between IPP size and csPCa found on TB was not significant; however, large IPP is associated with a significantly lower rate of csPCa detection than 0 IPP (p=0.007). Every mm increase in IPP is associated with a 5.6% decrease in the odds of csPCa detection on TB (p=0.004) and a 66.5% decrease in odds of detection in large IPP compared to 0 IPP (p=0.003). CONCLUSIONS: As the size of the IPP and volume increase, there is a decrease in the detection rate of csPCa on MRI-guided TB. These findings may be driven by poor MRI-TRUS co-registration and prostate asymmetry.
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Próstata , Neoplasias da Próstata , Humanos , Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Sharps and needlestick injuries pose a serious risk to operating theatre personnel with considerable morbidity, mortality and healthcare implications. The cost of prophylaxis and post-exposure treatment is a significant institutional economic burden. AIM: The aim of the review was to identify the prevalence of sharps and needlestick injury within the operating theatre and to establish the most common critical steps. METHOD: A systematic literature search was conducted. Abstracts of all studies published in English from 2015 onwards exploring sharps and needlestick injury within the operating theatre were reviewed. Primary outcome measure was sharps and needlestick injury prevalence. Secondary outcome measures included operational steps resulting in sharps and needlestick injury and costs of sharps and needlestick injury management. RESULTS: Sixteen studies were identified and included in analysis. Cross-sectional studies reported a pooled prevalence of 41.5% (n = 537; 95% confidence interval = 15.961 to 70.220). Retrospective data analysis reported an annualised prevalence of 5.027% (95% confidence interval = 0.676 to 13.073) on a total pooled sample population of 12,929. Further analysis of operational steps identified a 22% prevalence (n= 3460; 95% confidence interval = 14.2 to 31.3) of sharps and needlestick injury occurring during a procedure involving handing or receiving an instrument. CONCLUSION: Sharps and needlestick injuries are a significant but preventable risk in the operating theatre. Further research into the development of safety devices to reduce injury during instrument transfer is paramount.
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Ferimentos Penetrantes Produzidos por Agulha , Humanos , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Salas Cirúrgicas , Prevalência , Estudos Transversais , Estudos RetrospectivosRESUMO
BACKGROUND: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. MATERIALS AND METHODS: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautics and Space Administration (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. RESULTS: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. CONCLUSIONS: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.
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Armas Nucleares , Exposição à Radiação , Biologia , Feminino , Humanos , Masculino , Centrais Nucleares , Exposição à Radiação/efeitos adversos , RadiometriaRESUMO
This article presents the principles of an adaptive mixed reality rehabilitation (AMRR) system, as well as the training process and results from 2 stroke survivors who received AMRR therapy, to illustrate how the system can be used in the clinic. The AMRR system integrates traditional rehabilitation practices with state-of-the-art computational and motion capture technologies to create an engaging environment to train reaching movements. The system provides real-time, intuitive, and integrated audio and visual feedback (based on detailed kinematic data) representative of goal accomplishment, activity performance, and body function during a reaching task. The AMRR system also provides a quantitative kinematic evaluation that measures the deviation of the stroke survivor's movement from an idealized, unimpaired movement. The therapist, using the quantitative measure and knowledge and observations, can adapt the feedback and physical environment of the AMRR system throughout therapy to address each participant's individual impairments and progress. Individualized training plans, kinematic improvements measured over the entire therapy period, and the changes in relevant clinical scales and kinematic movement attributes before and after the month-long therapy are presented for 2 participants. The substantial improvements made by both participants after AMRR therapy demonstrate that this system has the potential to considerably enhance the recovery of stroke survivors with varying impairments for both kinematic improvements and functional ability.
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Biorretroalimentação Psicológica/métodos , Terapia da Realidade/métodos , Reabilitação do Acidente Vascular Cerebral , Interface Usuário-Computador , Fenômenos Biomecânicos , Humanos , Masculino , Movimento , Acidente Vascular Cerebral/fisiopatologia , Extremidade Superior/fisiopatologiaRESUMO
Purpose: Clinicians rely on imaging features to calculate complexity of renal masses based on validated scoring systems. These scoring methods are labor-intensive and are subjected to interobserver variability. Artificial intelligence has been increasingly utilized by the medical community to solve such issues. However, developing reliable algorithms is usually time-consuming and costly. We created an international community-driven competition (KiTS19) to develop and identify the best system for automatic segmentation of kidneys and kidney tumors in contrast CT and report the results. Methods: A training and test set of CT scans that was manually annotated by trained individuals were generated from consecutive patients undergoing renal surgery for whom demographic, clinical and outcome data were available. The KiTS19 Challenge was a machine learning competition hosted on grand-challenge.org in conjunction with an international conference. Teams were given 3 months to develop their algorithm using a full-annotated training set of images and an unannotated test set was released for 2 weeks from which average Sørensen-Dice coefficient between kidney and tumor regions were calculated across all 90 test cases. Results: There were 100 valid submissions that were based on deep neural networks but there were differences in pre-processing strategies, architectural details, and training procedures. The winning team scored a 0.974 kidney Dice and a 0.851 tumor Dice resulting in 0.912 composite score. Automatic segmentation of the kidney by the participating teams performed comparably to expert manual segmentation but was less reliable when segmenting the tumor. Conclusion: Rapid advancement in automated semantic segmentation of kidney lesions is possible with relatively high accuracy when the data is released publicly, and participation is incentivized. We hope that our findings will encourage further research that would enable the potential of adopting AI into the medical field.
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There is a large body of literature linking anatomic and geometric characteristics of kidney tumors to perioperative and oncologic outcomes. Semantic segmentation of these tumors and their host kidneys is a promising tool for quantitatively characterizing these lesions, but its adoption is limited due to the manual effort required to produce high-quality 3D segmentations of these structures. Recently, methods based on deep learning have shown excellent results in automatic 3D segmentation, but they require large datasets for training, and there remains little consensus on which methods perform best. The 2019 Kidney and Kidney Tumor Segmentation challenge (KiTS19) was a competition held in conjunction with the 2019 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) which sought to address these issues and stimulate progress on this automatic segmentation problem. A training set of 210 cross sectional CT images with kidney tumors was publicly released with corresponding semantic segmentation masks. 106 teams from five continents used this data to develop automated systems to predict the true segmentation masks on a test set of 90 CT images for which the corresponding ground truth segmentations were kept private. These predictions were scored and ranked according to their average Sørensen-Dice coefficient between the kidney and tumor across all 90 cases. The winning team achieved a Dice of 0.974 for kidney and 0.851 for tumor, approaching the inter-annotator performance on kidney (0.983) but falling short on tumor (0.923). This challenge has now entered an "open leaderboard" phase where it serves as a challenging benchmark in 3D semantic segmentation.
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Neoplasias Renais , Tomografia Computadorizada por Raios X , Estudos Transversais , Humanos , Processamento de Imagem Assistida por Computador , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagemRESUMO
BACKGROUND & AIMS: This study aimed to determine the prognostic significance of low muscle volume (LMV) Bioelectrical Impedance Analysis (BIA), defined skeletal muscle index (SMI, Kg/m2 male ≤8.75, female ≤5.75) in patients undergoing potentially curative surgery for Oesophageal Cancer (OC). METHODS: A prospective study of 122 patients diagnosed with OC [median age 65 yr, 104 male, 65 neoadjuvant therapy] who underwent preoperative BIA (Maltron Bioscan 920). Primary outcome measure was Overall Survival (OS). RESULTS: LMV was identified in 11 (9.0%) of patients, which was associated with low lean muscle mass (27.3 vs. 31.1 kg, p = 0.012), low body fat (8.8 vs.19.3 kg, p < 0.001), and greater total body water (72.2 vs. 62.2%, p = 0.001), and more open & close laparotomies (36.4 vs. 8.1%, p = 0.012). Median and 5-year OS was 16 months and 18.2% in LMV patients, compared with 51 months and 52.4% in non-sarcopenic patients (p = 0.002). On multivariable analysis of pre-operative variables, only LMV (HR 2.75; 95% CI 1.33-5.66, p = 0.006) was associated with OS. CONCLUSION: BIA is an important prognostic indicator in OC and focused pre-habilitation consequently has strong potential.
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Neoplasias Esofágicas , Tecido Adiposo , Idoso , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Músculo Esquelético , Prognóstico , Estudos ProspectivosRESUMO
Objective: To understand better the public perception and comprehension of medical technology such as artificial intelligence (AI) and robotic surgery. In addition to this, to identify sensitivity to their use to ensure acceptability and quality of counseling. Subjects and Methods: A survey was conducted on a convenience sample of visitors to the MN Minnesota State Fair (n = 264). Participants were randomized to receive one of two similar surveys. In the first, a diagnosis was made by a physician and in the second by an AI application to compare confidence in human and computer-based diagnosis. Results: The median age of participants was 45 (interquartile range 28-59), 58% were female (n = 154) vs 42% male (n = 110), 69% had completed at least a bachelor's degree, 88% were Caucasian (n = 233) vs 12% ethnic minorities (n = 31) and were from 12 states, mostly from the Upper Midwest. Participants had nearly equal trust in AI vs physician diagnoses. However, they were significantly more likely to trust an AI diagnosis of cancer over a doctor's diagnosis when responding to the version of the survey that suggested that an AI could make medical diagnoses (p = 9.32e-06). Though 55% of respondents (n = 145) reported that they were uncomfortable with automated robotic surgery, the majority of the individuals surveyed (88%) mistakenly believed that partially autonomous surgery was already happening. Almost all (94%, n = 249) stated that they would be willing to pay for a review of medical imaging by an AI if available. Conclusion: Most participants express confidence in AI providing medical diagnoses, sometimes even over human physicians. Participants generally express concern with surgical AI, but they mistakenly believe that it is already being performed. As AI applications increase in medical practice, health care providers should be cognizant of the potential amount of misinformation and sensitivity that patients have to how such technology is represented.
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Medicina , Robótica , Inteligência Artificial , Feminino , Humanos , Masculino , Minnesota , Opinião Pública , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Perifosine, an investigational, oral, synthetic alkylphospholipid, inhibits signal transduction pathways of relevance in multiple myeloma (MM) including PI3K/Akt. Perifosine demonstrated anti-MM activity in preclinical studies and encouraging early-phase clinical activity in combination with bortezomib. A randomized, double-blind, placebo-controlled phase 3 study was conducted to evaluate addition of perifosine to bortezomib-dexamethasone in MM patients with one to four prior therapies who had relapsed following previous bortezomib-based therapy. The primary endpoint was progression-free survival (PFS). The study was discontinued at planned interim analysis, with 135 patients enrolled. Median PFS was 22.7 weeks (95% confidence interval 16·0-45·4) in the perifosine arm and 39.0 weeks (18.3-50.1) in the placebo arm (hazard ratio 1.269 [0.817-1.969]; P = .287); overall response rates were 20% and 27%, respectively. Conversely, median overall survival (OS) was 141.9 weeks and 83.3 weeks (hazard ratio 0.734 [0.380-1.419]; P = .356). Overall, 61% and 55% of patients in the perifosine and placebo arms reported grade 3/4 adverse events, including thrombocytopenia (26% vs 14%), anemia (7% vs 8%), hyponatremia (6% vs 8%), and pneumonia (9% vs 3%). These findings demonstrate no PFS benefit from the addition of perifosine to bortezomib-dexamethasone in this study of relapsed/refractory MM, but comparable safety and OS.
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The pilot urine plutonium bioassay testing program engaged 100 atomic veterans and 58 persons representative of the United States general population using the fission track analysis technique, developed by Brookhaven National Laboratory. The methodology, collected data, scientific challenges, and test results are presented herein. The Defense Threat Reduction Agency and its predecessor agencies conducted this program in the late 1990s to the mid-2000s to determine the feasibility of bioassay testing to supplement dose reconstruction to estimate atomic veterans' doses under the agency's Nuclear Test Personnel Review Program. In summary, Pu urine bioassay using fission track analysis showed inconsistencies in sample measurement repeatability. To use the analysis as a tool to enhance current processes to perform accurate dose reconstructions requires extensive understanding and resolution of the measurement inconsistencies well beyond the scope of this pilot study. Therefore, fission track analysis (FTA) was found not feasible for implementation on a wide scale basis for atomic veterans.
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Armas Nucleares , Plutônio/urina , Veteranos/estatística & dados numéricos , Adulto , Bioensaio , Humanos , Exposição por Inalação/estatística & dados numéricos , Japão/epidemiologia , Masculino , Exposição à Radiação/análise , Reprodutibilidade dos Testes , Estados Unidos/etnologiaRESUMO
In contrast to vitamin K antagonists, no routine coagulation monitoring is required in patients taking non-vitamin-K oral anticoagulants (NOACs). However, dosing must take into account factors such as patient age, renal function, and accompanying haemorrhagic risk. There has been considerable debate about when laboratory measurement might be appropriate and which tests should be used. A workshop at the European Medicines Agency recently discussed the evidence about laboratory measurement from formal studies, clinical experience, and the multiple perspectives on NOAC treatment, and considered how our knowledge might be further enhanced.
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Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Cardiologia/educação , Educação Médica , Sociedades Médicas , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Europa (Continente) , Humanos , Acidente Vascular Cerebral/sangueRESUMO
There are many decisions and risks associated with the design and development of new pharmaceutical agents. To help improve decision-making, and reduce the associated risks--prior to synthesis, we have developed interactive web-browser tools for: (i) tracking, searching, clustering and categorizing (by reactive moieties) chemical reactants, (ii) interactively assessing risks, either synthetic--based on prior experience, absorption following oral administration--based on rules of 5, or diversity, and (iii) a complete architecture for enumerating, analyzing, submitting and plating large combinatorial or small biased libraries. We believe the implementation of this highly interactive system has given our scientists a competitive advantage by maintaining their focus on the lowest risk, highest quality molecules throughout the research process.
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Química Farmacêutica/métodos , Metodologias Computacionais , Software , Administração Oral , Disponibilidade Biológica , Técnicas de Química Combinatória , Relação Quantitativa Estrutura-Atividade , Medição de RiscoRESUMO
Openness and transparency are important considerations for medicines regulators, where public health is of paramount concern. As part of their commitment to transparency, the European Medicines Agency (EMA) and Therapeutic Goods Administration (TGA) in Australia publish information relating to their evaluation of medicines via public assessment reports. European Public Assessment Reports (EPARs) and Australian Public Assessment Reports (AusPARs) provide information about the considerations that led the regulator to approve or refuse the application. The reports summarise assessments by each regulator of the information provided on the quality, safety, and efficacy of the medicine under evaluation. Here, we describe the experiences of two established medicines regulators in publishing public assessment reports, and reflect on their future role in communicating medicines information.
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Participação da Comunidade , Controle de Medicamentos e Entorpecentes , Austrália , Comunicação , Europa (Continente) , HumanosRESUMO
Men who have sex with men (MSM) are a priority population for HIV care and prevention programs. This report describes HIV and other sexually transmitted disease (STD) trends among MSM in metropolitan Atlanta by analyzing nine databases. We describe the use of the male-to-female (M:F) ratio, a surrogate marker for MSM in databases without standardized MSM variables that is recommended as an indirect measure of HIV risk behavior in the CDC/HRSA Integrated Guidelines for Developing Epidemiologic Profiles. During 1997 to 2001, there were increases among MSM for reported syphilis (from 9% to 17%), anti-biotic-resistant gonorrhea (from 4.8% to 8.6%), and HIV seroprevalence (from 33% to 43%). During 1998 to 2001, the M:F ratio for cases peaked at 12:1 during a hepatitis A outbreak among MSM, increased for shigellosis (from 1:0 to 18:1) and giardiasis (from 1.7 to 2.1), and did not appreciably change for hepatitis B, salmonellosis, or chlamydia. HIV and several other STDs appear to have increased among MSM in metropolitan Atlanta. When standardized MSM variables are not available, an M:F ratio is useful.
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Doenças Transmissíveis/epidemiologia , Homossexualidade Masculina , Comportamento Sexual , Infecções Sexualmente Transmissíveis/transmissão , Adolescente , Adulto , Criança , Bases de Dados como Assunto , Feminino , Georgia/epidemiologia , Heterossexualidade , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
This systematic review and meta-analysis was performed to determine the influence of enhanced recovery programmes (ERPs) on outcomes after gastric cancer surgery. Medline, Embase, the Cochrane library and ClinicalTrials.gov were searched for studies on outcomes of gastrectomy in enhanced recovery or fast-track programmes. The primary outcome measure was post-operative duration of hospital stay (LOHS), and secondary outcome measures were selected based inclusion in two or more studies. Statistical analysis was performed using standardized mean difference (SMD) and odds ratio (OR) as the summary statistics. Fourteen studies, totalling 1676 patients with gastric cancer were analysed, including nine randomized trials. LOHS was significantly shorter after ERP when compared with control patients (CON, SMD -1.10, 95% confidence interval -1.56 to -0.65, p < 0.001), but with significant heterogeneity between studies (I(2) = 93%, p < 0.001). ERP was also associated with reduced serum inflammatory response (CRP: SMD -0.68 (-1.16 to -0.19), p = 0.007; IL-6: SMD -0.62 (-0.94 to -0.29), p < 0.001), less weight loss (SMD -0.79 (-1.11 to -0.46), p < 0.001), and lower cost (SMD -1.02 (-1.59 to -0.45), p < 0.001), as well as a trend toward shorter duration of intravenous infusion (SMD -2.70 (-5.35 to -0.05), p = 0.05). Inclusion in an ERP was not associated with increased post-operative morbidity (OR 0.83 (0.65 to 1.06), p = 0.13) or hospital readmission (OR 1.67 (0.88 to 3.19), p = 0.12). From this review the authors concluded that multimodal, standardized perioperative gastrectomy care appears feasible, safe and cost effective.
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Gastrectomia , Assistência Perioperatória/métodos , Neoplasias Gástricas/cirurgia , Humanos , Tempo de Internação , Fatores de TempoRESUMO
Active surveillance for laboratory-confirmed Yersinia enterocolitica (YE) infections was conducted at 5 Foodborne Diseases Active Surveillance Network (FoodNet) sites in the United States during 1996-1999. The annual incidence averaged 0.9 cases/100,000 population. After adjusting for missing data, the average annual incidence by race/ethnicity was 3.2 cases/100,000 population among black persons, 1.5 cases/100,000 population among Asian persons, 0.6 cases/100,000 population among Hispanic persons, and 0.4 cases/100,000 population among white persons. Incidence increased with decreasing age in all race/ethnicity groups. Black infants had the highest incidence (141.9 cases/100,000 population; range, 8.7 cases/100,000 population in Minnesota to 207.0 cases/100,000 population in Georgia). Seasonal variations in incidence, with a marked peak in December, were noted only among black persons. YE infections should be suspected in black children with gastroenteritis, particularly during November-February. Culturing for YE should be part of routine testing of stool specimens by clinical laboratories serving populations at risk, especially during the winter months.
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Yersiniose/epidemiologia , Yersinia enterocolitica , Negro ou Afro-Americano , Povo Asiático , Criança , Hispânico ou Latino , Humanos , Lactente , Vigilância da População , Fatores de Risco , Estações do Ano , Estados Unidos/epidemiologia , Estados Unidos/etnologia , Yersiniose/etnologiaRESUMO
The U.S. military consists of five armed services: the Army, Navy, Marine Corps, Air Force, and Coast Guard. It directly employs 1.4 million active duty military, 1.3 million National Guard and reserve military, and 700,000 civilian individuals. This paper describes the military guidance used to preserve and maintain the health of military personnel while they accomplish necessary and purposeful work in areas where they are exposed to radiation. It also discusses military exposure cohorts and associated radiogenic disease compensation programs administered by the U.S. Department of Veterans Affairs, the U.S. Department of Justice, and the U.S. Department of Labor. With a few exceptions, the U.S. military has effectively employed ionizing radiation since it was first introduced during the Spanish-American War in 1898. The U.S military annually monitors 70,000 individuals for occupational radiation exposure: ~2% of its workforce. In recent years, the Departments of the Navy (including the Marine Corps), the Army, and the Air Force all have a low collective dose that remains close to 1 person-Sv annually. Only a few Coast Guard individuals are now routinely monitored for radiation exposure. As with the nuclear industry as a whole, the Naval Reactors program has a higher collective dose than the remainder of the U.S. military. The U.S. military maintains occupational radiation exposure records on over two million individuals from 1945 through the present. These records are controlled in accordance with the Privacy Act of 1974 but are available to affected individuals or their designees and other groups performing sanctioned epidemiology studies.Introduction of Radiation Exposure of U.S. Military Individuals (Video 2:19, http://links.lww.com/HP/A30).
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Exposição Ambiental/análise , Militares , Adulto , Criança , Estudos de Coortes , Compensação e Reparação , Exposição Ambiental/efeitos adversos , Exposição Ambiental/economia , Humanos , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Exposição Ocupacional/economia , Lesões por Radiação/economia , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Estados UnidosRESUMO
PURPOSE: (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) is now established as a routine staging investigation of oesophageal cancer (OC). The aim of the study was to determine the prognostic significance of PET/CT defined tumour variables including maximum standardised uptake value (SUVmax), tumour length (TL), metastatic length of disease (MLoD), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and total local nodal metastasis count (PET/CT LNMC). MATERIALS AND METHODS: 103 pre-treatment OC patients (76 adenocarcinoma, 25 squamous cell carcinoma, 1 poorly differentiated and 1 neuroendocrine tumour) were staged using PET/CT. The prognostic value of the measured tumour variables were tested using log-rank analysis of the Kaplan-Meier method and Cox's proportional hazards method. Primary outcome measure was survival from diagnosis. RESULTS: Univariate analysis showed all variables to have strong statistical significance in relation to survival. Multivariate analysis demonstrated three variables that were significantly and independently associated with survival; MLoD (HR 1.035, 95% CI 1.008-1.064, p=0.011), TLG (HR 1.002, 95% CI 1.000-1.003, p=0.018) and PET/CT LNMC (HR 0.048-0.633, 95% CI 0.005-2.725, p=0.015). CONCLUSION: MLoD, TLG, and PET/CT LNMC are important prognostic indicators in OC. This is the first study to demonstrate an independent statistical association between TLG, MLoD and survival by multivariable analysis, and highlights the value of staging OC patients with PET/CT using functional tumour variables.
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Carcinoma/patologia , Carcinoma/secundário , Neoplasias Esofágicas/patologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Carcinoma/terapia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Prognóstico , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e EspecificidadeRESUMO
The aqueous solution structure of protoxin II (ProTx II) indicated that the toxin comprises a well-defined inhibitor cystine knot (ICK) backbone region and a flexible C-terminal tail region, similar to previously described NaSpTx III tarantula toxins. In the present study we sought to explore the structure-activity relationship of the two regions of the ProTx II molecule. As a first step, chimeric toxins of ProTx II and PaTx I were synthesized and their biological activities on Nav1.7 and Nav1.2 channels were investigated. Other tail region modifications to this chimera explored the effects of tail length and tertiary structure on sodium channel activity. In addition, the activity of various C-terminal modifications of the native ProTx II was assayed and resulted in the identification of protoxin II-NHCH3, a molecule with greater potency against Nav1.7 channels (IC50=42 pM) than the original ProTx II.
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Canal de Sódio Disparado por Voltagem NAV1.7/fisiologia , Peptídeos/química , Venenos de Aranha/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Animais , Células HEK293 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Peptídeos/síntese química , Peptídeos/farmacologia , Ratos , Venenos de Aranha/síntese química , Venenos de Aranha/farmacologia , Relação Estrutura-Atividade , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese química , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologiaRESUMO
BACKGROUND: Adaptive mixed reality rehabilitation (AMRR) is a novel integration of motion capture technology and high-level media computing that provides precise kinematic measurements and engaging multimodal feedback for self-assessment during a therapeutic task. OBJECTIVE: We describe the first proof-of-concept study to compare outcomes of AMRR and traditional upper-extremity physical therapy. METHODS: Two groups of participants with chronic stroke received either a month of AMRR therapy (n = 11) or matched dosing of traditional repetitive task therapy (n = 10). Participants were right handed, between 35 and 85 years old, and could independently reach to and at least partially grasp an object in front of them. Upper-extremity clinical scale scores and kinematic performances were measured before and after treatment. RESULTS: Both groups showed increased function after therapy, demonstrated by statistically significant improvements in Wolf Motor Function Test and upper-extremity Fugl-Meyer Assessment (FMA) scores, with the traditional therapy group improving significantly more on the FMA. However, only participants who received AMRR therapy showed a consistent improvement in kinematic measurements, both for the trained task of reaching to grasp a cone and the untrained task of reaching to push a lighted button. CONCLUSIONS: AMRR may be useful in improving both functionality and the kinematics of reaching. Further study is needed to determine if AMRR therapy induces long-term changes in movement quality that foster better functional recovery.