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AIMS: To evaluate the ability of logistic regression and machine learning methods to predict active arterial extravasation on computed tomographic angiography (CTA) in patients with acute gastrointestinal hemorrhage using clinical variables obtained prior to image acquisition. MATERIALS AND METHODS: CT angiograms performed for the indication of gastrointestinal bleeding at a single institution were labeled retrospectively for the presence of arterial extravasation. Positive and negative cases were matched for age, gender, time period, and site using Propensity Score Matching. Clinical variables were collected including recent history of gastrointestinal bleeding, comorbidities, laboratory values, and vitals. Data were partitioned into training and testing datasets based on the hospital site. Logistic regression, XGBoost, Random Forest, and Support Vector Machine classifiers were trained and five-fold internal cross-validation was performed. The models were validated and evaluated with the area under the receiver operating characteristic curve. RESULTS: Two-hundred and thirty-one CTA studies with arterial gastrointestinal extravasation were 1:1 matched with 231 negative studies (N=462). After data preprocessing, 389 patients and 36 features were included in model development and analysis. Two hundred and fifty-five patients (65.6%) were selected for the training dataset. Validation was performed on the remaining 134 patients (34.4%); the area under the receiver operating characteristic curve for the logistic regression, XGBoost, Random Forest, and Support Vector Machine classifiers was 0.82, 0.68, 0.54, and 0.78, respectively. CONCLUSION: Logistic regression and machine learning models can accurately predict presence of active arterial extravasation on CTA in patients with acute gastrointestinal bleeding using clinical variables.
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Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.
Subject(s)
Brain Mapping , Magnetic Resonance Imaging , Humans , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Brain , Parietal Lobe/diagnostic imaging , Cerebral CortexABSTRACT
BACKGROUND: Guideline recommendations for the treatment of breast cancer with low hormone receptor (HR) expression (1%-9%) are ambiguous and several studies showed more similarities with HR-negative tumors than with HR strongly positive tumors (≥10%). We used a population-based 15-year cohort to compare patient characteristics and outcome of HR low positive tumors with HR-negative and HR strongly positive tumors, respectively. PATIENTS AND METHODS: A total of 38 560 women diagnosed with early invasive breast cancer between 2004 and 2018 within the scope of the Munich Cancer Registry with 4.9 million inhabitants were included. Descriptive analyses of prognostic factors, treatment, and outcome analyses using the Kaplan-Meier method; cumulative incidence in consideration of competing risks; and multivariate analyses (Cox regression and Fine-Gray model) were conducted. Endpoints were time to local recurrence (TTLR), time to lymph node recurrence (TTLNR), time to metastasis (TTM), overall survival (OS), and relative survival (RS). RESULTS: A total of 861 patients (2%) had HR low positive, 4862 (13%) HR-negative, and 32 837 (85%) HR strongly positive tumors. Within the HER2-negative cohort (n = 33 366), survival of HR low positive tumors was significantly worse than that of HR strongly positive tumors [OS hazard ratio 0.66 (95% confidence interval 0.55-0.78)], whereas between HR low positive and HR-negative tumors no significant survival difference could be detected [OS hazard ratio 0.93 (95% confidence interval 0.78-1.11)]. TTLR, TTLNR, and TTM showed similar results. By contrast, within the HER2-positive cohort (n = 5194), no statistically significant differences between the three HR groups could be detected in multivariate analyses. CONCLUSION: Current definitions for HR positivity and its clinical relevance should be reconsidered. Patients with HR low positive/HER2-negative tumors could be regarded and treated similar to patients with triple-negative tumors.
Subject(s)
Breast Neoplasms , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Female , Hormones , Humans , Neoplasm Recurrence, Local , Prognosis , Receptor, ErbB-2 , Receptors, ProgesteroneABSTRACT
BACKGROUND: A multi-cancer early detection (MCED) test used to complement existing screening could increase the number of cancers detected through population screening, potentially improving clinical outcomes. The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) was a prospective, case-controlled, observational study and demonstrated that a blood-based MCED test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin (CSO) with high accuracy. The objective of this third and final CCGA substudy was to validate an MCED test version further refined for use as a screening tool. PATIENTS AND METHODS: This pre-specified substudy included 4077 participants in an independent validation set (cancer: n = 2823; non-cancer: n = 1254, non-cancer status confirmed at year-one follow-up). Specificity, sensitivity, and CSO prediction accuracy were measured. RESULTS: Specificity for cancer signal detection was 99.5% [95% confidence interval (CI): 99.0% to 99.8%]. Overall sensitivity for cancer signal detection was 51.5% (49.6% to 53.3%); sensitivity increased with stage [stage I: 16.8% (14.5% to 19.5%), stage II: 40.4% (36.8% to 44.1%), stage III: 77.0% (73.4% to 80.3%), stage IV: 90.1% (87.5% to 92.2%)]. Stage I-III sensitivity was 67.6% (64.4% to 70.6%) in 12 pre-specified cancers that account for approximately two-thirds of annual USA cancer deaths and was 40.7% (38.7% to 42.9%) in all cancers. Cancer signals were detected across >50 cancer types. Overall accuracy of CSO prediction in true positives was 88.7% (87.0% to 90.2%). CONCLUSION: In this pre-specified, large-scale, clinical validation substudy, the MCED test demonstrated high specificity and accuracy of CSO prediction and detected cancer signals across a wide diversity of cancers. These results support the feasibility of this blood-based MCED test as a complement to existing single-cancer screening tests. CLINICAL TRIAL NUMBER: NCT02889978.
Subject(s)
Early Detection of Cancer , Neoplasms , Biomarkers, Tumor/genetics , DNA Methylation , Humans , Neoplasms/diagnosis , Neoplasms/genetics , Oncogenes , Prospective StudiesABSTRACT
BACKGROUND: Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. PARTICIPANTS AND METHODS: The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. RESULTS: Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I-III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for â¼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. CONCLUSIONS: cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.
Subject(s)
Cell-Free Nucleic Acids , Neoplasms , Biomarkers, Tumor , Cell-Free Nucleic Acids/genetics , DNA Methylation , DNA, Neoplasm/genetics , Female , Humans , Neoplasms/diagnosis , Neoplasms/genetics , Prospective StudiesABSTRACT
BACKGROUND: Enzalutamide and apalutamide are potent next-generation androgen receptor (AR) antagonists used in metastatic and non-metastatic prostate cancer. Metabolic, hormonal and immunologic effects of deep AR suppression are unknown. We hypothesized that enzalutamide and apalutamide suppress 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD2), which normally converts cortisol to cortisone, leading to elevated cortisol concentrations, increased ratio of active to inactive glucocorticoids and possibly suboptimal response to immunotherapy. On-treatment glucocorticoid changes might serve as an indicator of active glucocorticoid exposure and resultant adverse consequences. PATIENTS AND METHODS: Human kidney tissues were stained for AR and 11ß-HSD2 expression. Patients in three trials [neoadjuvant apalutamide plus leuprolide, enzalutamide ± PROSTVAC (recombinant poxvirus prostate-specific antigen vaccine) for metastatic castration-resistant prostate cancer (CRPC) and enzalutamide ± PROSTVAC for non-metastatic castration-sensitive prostate cancer] were analyzed for cortisol and its metabolites using liquid chromatography-mass spectrometry (LC-MS/MS). Progression-free survival was determined in the metastatic CRPC study of enzalutamide ± PROSTVAC for those with glucocorticoid changes above and below the median. RESULTS: Concurrent AR and 11ß-HSD2 expression occurs only in the kidneys of men. A statistically significant rise in cortisol concentration, cortisol/cortisone ratio and tetrahydrocortisol/tetrahydrocortisone ratio with AR antagonist treatment occurred uniformly across all three trials. In the trial of enzalutamide ± PROSTVAC for metastatic CRPC, high cortisol/cortisone ratio in the enzalutamide arm was associated with significantly improved progression-free survival. However, in the enzalutamide + PROSTVAC arm, the opposite trend was observed. CONCLUSION: Enzalutamide and apalutamide treatment toggles renal 11ß-HSD2 and significantly increases indicators of and exposure to biologically active glucocorticoids, which is associated with clinical outcomes.
Subject(s)
Prostatic Neoplasms, Castration-Resistant , Prostatic Neoplasms , Chromatography, Liquid , Glucocorticoids , Humans , Kidney , Male , Prostatic Neoplasms, Castration-Resistant/drug therapy , Receptors, Androgen/genetics , Tandem Mass SpectrometryABSTRACT
We detected a long-term transient deformation signal between 2014 and 2016 in the Atacama region (Chile) using survey Global Positioning System (GPS) observations. Over an â¼150 km along-strike region, survey GPS measurements in 2014 and 2016 deviate significantly from the interseismic trend estimated using previous observations. This deviation from steady state deformation is spatially coherent and reveals a horizontal westward diverging motion of several centimeters, along with a significant uplift. It is confirmed by continuous measurements of recently installed GPS stations. We discard instrumental, hydrological, oceanic, or atmospheric loading effects and show that the transient is likely due to deep slow slip in the transition zone of the subduction interface (â¼40- to 60-km depth). In addition, daily observations recorded by a continuous GPS station operating between 2002 and 2015 highlight similar transient signals in 2005 and 2009, suggesting a recurrent pattern.
ABSTRACT
BACKGROUND Statewide interventions are critical to meeting the goals of the National HIV/AIDS Strategy in this country. In 2012, the North Carolina Division of Public Health developed the North Carolina State Bridge Counselor program to improve linkage to and reengagement in care for newly diagnosed persons and persons living with HIV who were out-of-care.METHODS We reviewed the planning process for the North Carolina State Bridge Counselor program, which involved a review of existing strengths-based counseling models for persons living with HIV, implementation of these models, and communication strategies with other providers. State bridge counselor responsibilities were delineated from the role of disease intervention specialists while retaining the fieldwork capability of disease intervention specialists to conduct outreach and provide services for persons living with HIV throughout the state.RESULTS Program implementation required extensive planning with stakeholders, incorporation of strengths-based counseling models, development of performance standards, and utilization of CAREWare, an HIV care software program to document referrals and data-sharing between state bridge counselors and clinics. By the end of 2014, state bridge counselor services were provided to approximately 60 of the 400 persons living with HIV (15%) who are diagnosed each quarter in North Carolina, with increasing utilization of the program.LIMITATIONS We assessed the development of this intervention specific to the North Carolina Division of Public Health, which may limit its generalizability. However, the State Bridge Counselor program was implemented in both urban and rural areas throughout the state, which increases its applicability to different public health programs throughout the country.CONCLUSION We demonstrated that a statewide State Bridge Counselor program for linkage and reengagement activities can be implemented by leveraging existing infrastructures, electronic medical records, HIV care networks, and fieldwork activities.
Subject(s)
Counseling , HIV Infections/prevention & control , Health Services Accessibility , Patient Acceptance of Health Care , Patient Compliance , Referral and Consultation , HIV Infections/psychology , Health Plan Implementation , Humans , North CarolinaABSTRACT
More than 2 million visits for skin and soft tissue infections (SSTIs) are seen in US emergency departments (EDs) yearly. Up to 50% of patients with SSTIs, suffer from recurrences, but associated factors remain poorly understood. We performed a retrospective study of patients with primary diagnosis of SSTI between 2005 and 2011 using California ED discharge data from the State Emergency Department Databases and State Inpatient Databases. Using a multivariable logistic regression, we examined factors associated with a repeat SSTI ED visits up to 6 months after the initial SSTI. Among 197 371 SSTIs, 16·3% were associated with a recurrent ED visit. We found no trend in recurrent visits over time (χ 2 trend = 0·68, P = 0·4). Race/ethnicity, age, geographical location, household income, and comorbidities were all associated with recurrent visits. Recurrent ED visits were associated with drug/alcohol abuse or liver disease [odds ratio (OR) 1·4, 95% confidence interval (CI) 1·3-1·4], obesity (OR 1·3, 95% CI 1·2-1·4), and in infections that were drained (OR 1·1, 95% CI 1·1-1·1) and inversely associated with hospitalization after initial ED visit (OR 0·4, 95% CI 0·3-0·4). In conclusion, we found several patient-level factors associated with recurrent ED visits. Identification of these high-risk groups is critical for future ED-based interventions.
Subject(s)
Emergency Medical Services , Skin Diseases, Infectious/diagnosis , Skin Diseases, Infectious/epidemiology , Soft Tissue Infections/diagnosis , Soft Tissue Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , California/epidemiology , Child , Child, Preschool , Emergency Service, Hospital , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Recurrence , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: While work-related fatigue has become an issue of concern among European employees, the relationship between fatigue, depression and work-related stressors is far from clear. The purposes of this study were (1) to determine the associations of fatigue with work-related stressors, severe medical disease, health behavior and depression in the working population and (2) to determine the unique impact of work-related stressors on fatigue. METHODS: We used cross-sectional data of N = 7,930 working participants enrolled in the Gutenberg Health Study (GHS) from 2007 to 2012 filled out the Personal Burnout Scale (PBS) of the Copenhagen Psychosocial Questionnaire (COPSOQ), the PHQ-9, and a list of work-related stressors. RESULTS: A total of 27.5% reported increased fatigue, esp. women, younger persons with a lower social status and income, smokers, severely medically ill, previously and currently depressed participants. Fatigue was consistently associated with severe medical disease, health behavior and depression, which need to be taken into account as potential confounders when analyzing its relationship to work-related strains. Depression was consistently associated with work-related stressors. However, after statistically partialling out depression, fatigue was still significantly associated with work-related stress. CONCLUSIONS: Fatigue as an indicator of allostatic load is consistently associated with work-related stressors such as work overload after controlling for depression. The brief Personal Burn-out Scale is suitable for assessing work-related fatigue in the general population.
Subject(s)
Burnout, Professional/psychology , Employment/psychology , Fatigue/psychology , Occupational Stress/psychology , Adult , Cross-Sectional Studies , Depression/psychology , Female , Health Status , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Socioeconomic Factors , Surveys and QuestionnairesABSTRACT
Having a precise knowledge of the dispersal ability of a population in a heterogeneous environment is of critical importance in agroecology and conservation biology as it can provide management tools to limit the effects of pests or to increase the survival of endangered species. In this paper, we propose a mechanistic-statistical method to estimate space-dependent diffusion parameters of spatially-explicit models based on stochastic differential equations, using genetic data. Dividing the total population into subpopulations corresponding to different habitat patches with known allele frequencies, the expected proportions of individuals from each subpopulation at each position is computed by solving a system of reaction-diffusion equations. Modelling the capture and genotyping of the individuals with a statistical approach, we derive a numerically tractable formula for the likelihood function associated with the diffusion parameters. In a simulated environment made of three types of regions, each associated with a different diffusion coefficient, we successfully estimate the diffusion parameters with a maximum-likelihood approach. Although higher genetic differentiation among subpopulations leads to more accurate estimations, once a certain level of differentiation has been reached, the finite size of the genotyped population becomes the limiting factor for accurate estimation.
Subject(s)
Conservation of Natural Resources/methods , Ecosystem , Models, Biological , Animals , Computer Simulation , Gene Flow/genetics , Genetics, Population , Genotype , Likelihood FunctionsABSTRACT
Considering eye-fixation behavior is standard in reading research to investigate underlying cognitive processes. However, in numerical cognition research eye-tracking is used less often and less systematically. Nevertheless, we identified over 40 studies on this topic from the last 40 years with an increase of eye-tracking studies on numerical cognition during the last decade. Here, we review and discuss these empirical studies to evaluate the added value of eye-tracking for the investigation of number processing. Our literature review revealed that the way eye-fixation behavior is considered in numerical cognition research ranges from investigating basic perceptual aspects of processing non-symbolic and symbolic numbers, over assessing the common representational space of numbers and space, to evaluating the influence of characteristics of the base-10 place-value structure of Arabic numbers and executive control on number processing. Apart from basic results such as reading times of numbers increasing with their magnitude, studies revealed that number processing can influence domain-general processes such as attention shifting-but also the other way round. Domain-general processes such as cognitive control were found to affect number processing. In summary, eye-fixation behavior allows for new insights into both domain-specific and domain-general processes involved in number processing. Based thereon, a processing model of the temporal dynamics of numerical cognition is postulated, which distinguishes an early stage of stimulus-driven bottom-up processing from later more top-down controlled stages. Furthermore, perspectives for eye-tracking research in numerical cognition are discussed to emphasize the potential of this methodology for advancing our understanding of numerical cognition.
Subject(s)
Attention/physiology , Cognition/physiology , Fixation, Ocular/physiology , Mathematics , Executive Function , Humans , Neuropsychological Tests , Problem Solving , Reaction Time/physiologyABSTRACT
The injection locking properties of a newly developed waveguide-based external cavity semiconductor laser have been investigated. Using the injection locking properties to measure the Q-factor of complex optical cavities with unknown internal losses, has been demonstrated for the first time.
ABSTRACT
We report on the first cross section measurements for charged current coherent pion production by neutrinos and antineutrinos on argon. These measurements are performed using the ArgoNeuT detector exposed to the NuMI beam at Fermilab. The cross sections are measured to be 2.6(-1.0)(+1.2)(stat)(-0.4)(+0.3)(syst)×10(-38) cm(2)/Ar for neutrinos at a mean energy of 9.6 GeV and 5.5(-2.1)(+2.6)(stat)(-0.7)(+0.6)(syst)×10(-39) cm(2)/Ar for antineutrinos at a mean energy of 3.6 GeV.
ABSTRACT
One of the prevailing hypotheses suggests schizophrenia as a neurodevelopmental disorder, involving dysfunction of dopaminergic and glutamatergic systems. Accumulating evidence suggests mitochondria as an additional pathological factor in schizophrenia. An attractive model to study processes related to neurodevelopment in schizophrenia is reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and differentiating them into different neuronal lineages. iPSCs from three schizophrenia patients and from two controls were reprogrammed from hair follicle keratinocytes, because of their accessibility and common ectodermal origin with neurons. iPSCs were differentiated into Pax6(+)/Nestin(+) neural precursors and then further differentiated into ß3-Tubulin(+)/tyrosine hydroxylase(+)/DAT(+) dopaminergic neurons. In addition, iPSCs were differentiated through embryonic bodies into ß3-Tubulin(+)/Tbox brain1(+) glutamatergic neurons. Schizophrenia-derived dopaminergic cells showed severely impaired ability to differentiate, whereas glutamatergic cells were unable to maturate. Mitochondrial respiration and its sensitivity to dopamine-induced inhibition were impaired in schizophrenia-derived keratinocytes and iPSCs. Moreover, we observed dissipation of mitochondrial membrane potential (Δψm) and perturbations in mitochondrial network structure and connectivity in dopaminergic along the differentiation process and in glutamatergic cells. Our data unravel perturbations in neural differentiation and mitochondrial function, which may be interconnected, and of relevance to dysfunctional neurodevelopmental processes in schizophrenia.
Subject(s)
Hair Follicle/pathology , Induced Pluripotent Stem Cells/pathology , Keratinocytes/pathology , Mitochondria/metabolism , Neurogenesis , Neurons/pathology , Schizophrenia, Paranoid/pathology , Antigens, Differentiation/biosynthesis , Antigens, Differentiation/genetics , Cell Lineage , Cells, Cultured , Dopamine Agents/pharmacology , Ectoderm/cytology , Excitatory Amino Acid Agents/pharmacology , Gene Expression Regulation , Humans , Induced Pluripotent Stem Cells/metabolism , Membrane Potential, Mitochondrial , Models, Neurological , Nerve Tissue Proteins/biosynthesis , Nerve Tissue Proteins/genetics , Neurons/drug effects , Neurons/metabolism , Oxygen Consumption , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Schizophrenia, Paranoid/metabolismABSTRACT
This study aimed to investigate whether neurological patients presenting with a bias in line bisection show specific problems in bisecting a line into two equal parts or their line bisection bias rather reflects a special case of a deficit in proportional reasoning more generally. In the latter case, the bias should also be observed for segmentations into thirds or quarters. To address this question, six neglect patients with a line bisection bias were administered additional tasks involving horizontal lines (e.g., segmentation into thirds and quarters, number line estimation, etc.). Their performance was compared to five neglect patients without a line bisection bias, 10 patients with right hemispheric lesions without neglect, and 32 healthy controls. Most interestingly, results indicated that neglect patients with a line bisection bias also overestimated segments on the left of the line (e.g., one third, one quarter) when dissecting lines into parts smaller than halves. In contrast, such segmentation biases were more nuanced when the required line segmentation was framed as a number line estimation task with either fractions or whole numbers. Taken together, this suggests a generalization of line bisection bias towards a segmentation or proportional processing bias, which is congruent with attentional weighting accounts of line bisection/neglect. As such, patients with a line bisection bias do not seem to have specific problems bisecting a line, but seem to suffer from a more general deficit processing proportions.
Subject(s)
Functional Laterality , Perceptual Disorders , Humans , Perceptual Disorders/etiology , Attention , Bias , Generalization, Psychological , Space PerceptionABSTRACT
PURPOSE: To investigate whether reducing the volume of intravenous iodinated contrast material injected during brain computed tomography (CT) provides reliable and accurate imaging without compromising diagnostic accuracy. METHODS: This prospective study enrolled patients undergoing enhanced brain CT at a single tertiary hospital. Subjects who agreed to participate received a reduced dose of 60 ml contrast. The images were compared to an age and gender-matched control group who received the conventional 80 cc dose. Neuroradiologists assessed image quality and interpretation using a 5-point Likert scale with six specific domains. Based on ICC, inter-rater reliability was high at 0.873. Multiple linear regression predicted overall diagnostic accuracy based on contrast dose, age, and gender. Visual Grading Characteristics (VGC) analysis was also performed to quantify regional brain enhancement differences between the two contrast groups. RESULTS: The study included 47 patients in the 60 cc group and 55 in the 80 cc control group. The results showed the 80 cc group had significantly higher enhancement ratings compared to 60 cc for all six structures assessed. The differences between groups ranged from -0.241 to -0.433 (p < 0.001) on the 5-point scale.The VGC analysis confirmed significantly greater brain parenchymal enhancement in the 80 cc group compared to the 60 cc group. CONCLUSION: The findings indicate that reducing the intravenous iodinated contrast material volume during brain CT from 80 cc to 60 cc leads to a statistically significant reduction in image quality and diagnostic accuracy. Further research with larger cohorts is needed to confirm these findings and assess the clinical impact of these differences.
Subject(s)
Contrast Media , Tomography, X-Ray Computed , Humans , Male , Female , Contrast Media/administration & dosage , Tomography, X-Ray Computed/methods , Middle Aged , Prospective Studies , Reproducibility of Results , Aged , Adult , Injections, Intravenous , Brain/diagnostic imaging , Iodine/administration & dosage , Radiographic Image Enhancement/methodsABSTRACT
PURPOSE: Machine learning (ML) algorithms to predict cancer survival have recently been reported for a number of sarcoma subtypes, but none have investigated undifferentiated pleomorphic sarcoma (UPS). ML is a powerful tool that has the potential to better prognosticate UPS. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for cases of histologically confirmed undifferentiated pleomorphic sarcoma (UPS) (n = 665). Patient, tumor, and treatment characteristics were recorded, and ML models were developed to predict 1-, 3-, and 5-year survival. The best performing ML model was externally validated using an institutional cohort of UPS patients (n = 151). RESULTS: All ML models performed best at the 1-year time point and worst at the 5-year time point. On internal validation within the SEER cohort, the best models had c-statistics of 0.67-0.69 at the 5-year time point. The Multi-Layer Perceptron Neural Network (MLP) model was the best performing model and used for external validation. Similarly, the MLP model performed best at 1-year and worst at 5-year on external validation with c-statistics of 0.85 and 0.81, respectively. The MLP model was well calibrated on external validation. The MLP model has been made publicly available at https://rachar.shinyapps.io/ups_app/ . CONCLUSION: Machine learning models perform well for survival prediction in UPS, though this sarcoma subtype may be more difficult to prognosticate than other subtypes. Future studies are needed to further validate the machine learning approach for UPS prognostication.
Subject(s)
Sarcoma , Soft Tissue Neoplasms , Humans , Sarcoma/therapy , Algorithms , Soft Tissue Neoplasms/pathology , Machine LearningABSTRACT
Somatic mosaicism is present in slightly more than 50% of small supernumerary marker chromosome (sSMC) carriers. Interestingly, non-acrocentric derived sSMC show mosaicism much more frequently than acrocentric ones. sSMC can be present in different mosaic rates, which may go below 5% of the studied cells. Also cryptic mosaicism can be present and mosaics may be differently expressed in different tissues of the body. Even though in the overwhelming majority of the cases somatic sSMC mosaicism has no direct clinical effect, there are also cases with altered clinical outcomes due to mosaicism. Also clinically important is the fact that a de novo sSMC, even present in mosaic, may be a hint of uniparental disomy (UPD). As it is under discussion to possibly replace standard karyotyping by methods like array-CGH, the impracticality of the latter to detect low-level sSMC mosaics and/or UPD has to be considered as well. Overall, sSMC mosaicism has to be studied carefully in each individual case, as it can be extremely informative and of importance, especially for prenatal genetic counseling.