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Pythagoras and the ratios
An ancient Greek boy, Pythagoras, helps his cousins produce pleasant music when he adjusts the mathematical ratios between the part of their pipes and lyres, knowledge he would later use to become a famous philosopher.
Book
OR11-02 Functional Characterization Of Sdhb Variants Informs Clinical Classification And Reveals Genotype-phenotype Associations
Abstract
Disclosure: S. Lee: None. L. Needleman: None. J. Park: None. R. Schugar: None. J.P. Annes: None.
Pathogenic mutations in the succinate dehydrogenase complex, particularly in the SDHB gene, predispose individuals to hereditary pheochromocytoma and paraganglioma (hPPGL). However, more than 80% of missense SDHB variants are classified as variants of uncertain significance (VUS) in ClinVar. Consequently, numerous families harboring an SDHB VUS are at elevated oncologic risk, but do not benefit from early detection protocols. As SDHB pathogenicity is caused by impaired SDH enzymatic activity, functional evaluation may help resolve VUS classification. Hence, we developed a functional biochemical assay using CRISPR/Cas9-engineered SDHB-knockout HEK293 cells to assess succinate/fumarate ratios by LC-MS/MS as a proxy for SDH enzymatic activity. Loss of SDHB led to a marked elevation in the succinate/fumarate ratio, which was restored by transfection of wild-type SDHB. Expression of 35 classified variants (9 benign, 26 pathogenic) clustered into low and high succinate/fumarate ratio groups, validating the assay’s ability to resolve SDHB variant functionality. To improve interpretability, we converted succinate/fumarate ratios into SDH % activity, which was used for the logistic regression modeling of known variants. Using the trained model, P(path) and OddsPath values were calculated to assign ACMG/AMP functional evidence strength (BS3/PS3). Compared to the computational predictor REVEL, our assay provided superior discrimination between benign and pathogenic variants. This model was applied to 33 VUSs, including 16 Stanford patient alleles and three causative of Leigh syndrome. Twenty-three VUSs demonstrated wild-type-like activity (BS3), while 10 exhibited marked SDH dysfunction and were assigned PS3strong. Following ACMG/AMP guidelines, mock clinical interpretation that included our functional assay recategorized 78% of SDHB VUSs (16 likely benign and 10 likely pathogenic). Notably, all SDHB VUSs affecting highly conserved cysteine residues responsible for Fe-S cluster coordination showed complete enzymatic loss, confirming the critical function of these domains. Interestingly, recessive mitochondrial disease-associated SDHB variants (Leighs) were not reliably distinguished from wild-type-like variants, indicating these variants are not causative for hPPGL. Finally, pathogenic variants with relatively lower succinate/fumarate ratios than PPGL-predominant variants were associated with increased occurrence of head and neck paragangliomas (HNPGL; r2=0.45; p=0.0001). Logistic modeling identified a metabolic threshold predictive of tumor location; hence, SDH dysfunction severity influences location-specific tumor risk. Together, these data establish a robust, quantitative platform for SDHB variant classification with immediate clinical implications for risk assessment and tumor surveillance.
Presentation: Saturday, July 12, 2025
Journal Article
What are the chances? : probability, statistics, ratios, and proportions
\"Introduces the reader to probability, statistics, ratios and proportions.\"-- Provided by publisher.
Book
NP-002 Impact of blood sample handling during 99mTc-ceretec leukocyte labelling on image quality and interpretation
Context and ObjectiveIn vitro labelling of leukocytes with 99mTc-HMPAO is a haematological test performed and optimised in specialised radiopharmacies in some university hospitals. It is used to differentiate between infection on implanted devices and inflammation in cases of pain. However, it requires high-quality biological samples. Several factors, including those related to the patient and healthcare professionals, affect the outcome. This study aims to establish a link between sample quality and image quality to improve our practices and patient care.Materials and MethodsWe first established criteria to assess blood sample quality, such as the duration of collection, the type of equipment used, the puncture site, sedimentation time, hemolysis, and cell viability tests, alongside an associated score (≤2: excellent, 3≤ score ≤5: average, ≥6: poor). We then defined image quality criteria in the early phase, based on spleen/liver (S/L) activity ratios measured during imaging (a ratio <130% indicating good image quality, 130%–150% moderate quality, and >150% poor quality). Lastly, we statistically compared S/L ratios between two groups: good vs. average/poor samples.ResultsOut of 23 samples, 18 were rated ‘excellent,’ two ‘average,’ and three ‘poor.’ Among the ‘excellent’ samples, 17 had S/L ratios <130%, corresponding to good image quality, while one had a ratio >150%. Among the five ‘average/poor’ samples, one had an S/L ratio <130%, one between 130%–150%, and three >150%. A significant difference (P<0.05) was found between the good and average/poor sample groups.Conclusion/DiscussionOur results suggest that sample quality affects image quality. However, certain biases, such as the small sample size and the low proportion of ‘average/poor’ samples (5/23), should be considered. The choice of quality criteria and scoring system may need refinement. Additionally, the patient’s cell condition at the time of testing and the proximity of the suspected infection to organs like the liver and spleen may influence the results. A larger, long-term study could help develop optimal sampling recommendations.
Journal Article
Associations Between Routine Blood‐Derived Inflammatory Markers and 14‐Day Readmission After Total Hip Arthroplasty: An Exploratory Study
Objective Early readmission following total hip arthroplasty (THA) is not uncommon and impacts patient outcomes and healthcare costs. However, easily accessible biomarkers for early identification of high‐risk patients remain limited. This study aims to evaluate the association between various blood component‐derived ratios and 14‐day readmission after THA. Methods Data from the Chang Gung Medical Research Database (CGRD) from 2014 to 2022 were retrospectively analyzed. Patients ≥ 20 years old who underwent primary THA by a single surgeon were included. The primary outcome was 14‐day readmission. Five hematologic markers were evaluated: monocyte‐to‐albumin ratio (MAR), red cell distribution width (RDW)‐to‐albumin ratio (RAR), hemoglobin‐to‐albumin ratio (HAR), leukocyte‐to‐albumin ratio (LAR), and RDW‐to‐platelet ratio (RPR). Ratios were calculated from blood collected within 1 month before to 1 week after surgery. Receiver operating characteristic (ROC) Curve analysis was used to determine their optimal thresholds, and multivariable logistic regression assessed associations between these markers and readmission risk. Results A total of 307 patients were included in the analysis. Among the ratios evaluated, only high RPR (≥ 0.10; aOR = 5.92, 95% CI: 2.19–16.00, p = 0.001) was significantly associated with increased risk of 14‐day readmission after adjustment in the multivariable analysis. Conclusion RPR is independently associated with 14‐day readmission following THA in this exploratory study. As an easily obtainable marker, it may aid postoperative risk stratification, and the findings provide a foundation for future multicenter prospective investigations incorporating more granular perioperative factors and additional biomarkers before clinical application. RDW‐to‐platelet ratio (RPR) is strongly associated with 14‐day readmission following total hip arthroplasty. RPR could serve as a marker for patients at increased risk of early readmission.
Journal Article
Key management ratios : the 100+ ratios every manager needs to know
Business ratios are the figures that provide management with targets and standards for their organisation. From earnings per share and cash flow to return on investment and sales to fixed assets ratios, this book guides managers through the key ratios at the heart of business practice.
Book
Retrospective evaluation of hematological ratios in canine parvovirosis: 401 cases
Background The utility of neutrophil‐to‐lymphocyte ratio (NLR), platelet to‐lymphocyte ratio (PLR) and monocyte‐to‐lymphocyte ratio (MLR) as prognostic indicators has not been investigated in canine parvovirosis (CPV). Hypothesis To evaluate whether these hematological ratios obtained at hospital admission in CPV are associated with outcome or duration of hospitalization. Animals. Four hundred one client‐owned dogs presented with CPV. Methods‐Retrospective multicenter cohort study. Medical records were reviewed to identify dogs with CPV. Data regarding signalment, complete blood count at admission, duration of hospitalization and outcome were collected. Results Of the 401 dogs included in the study, 336 (83.8%) survived to discharge. The median (25th and 75th percentiles) PLR in nonsurvivors (336.56 [159.84‐635.77]) was significantly higher than in survivors (217.65 [117.67‐389.65]) (P = .003). The area under the receiver‐operating characteristic curve for nonsurvival was 0.615 (95% CI [0.593‐0.691], P = .003). A cut off of 700 showed a 21.5% sensitivity and 90% specificity for nonsurvival. No association was observed between hospitalization duration and either hematological ratios or total WBC counts. The median (25th and 75th percentiles) lymphocyte count was below reference interval in all dogs and was significantly lower in the dogs which died (0.82 × 109/L [0.5‐1.87]) than in survivors (1.27 × 109/L [0.73‐2.22]) (P = .005). The median (25th and 75th percentiles) monocyte count however was lower in survivors (0.38 × 109/L [0.29‐1.59]), than in nonsurvivors (0.73 × 109/L [0.1‐2]) (P = .002). Conclusions Evaluation of PLR at hospital admission might be a useful marker of disease severity and could have prognostic value in dogs with CPV.
Journal Article
Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: an observational cohort study
Background
The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART).
Methods
We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono).
Results
A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log
10
CD4/CD8 ratio for patients on dual therapy was −0.03 (95% confidence interval (CI) –0.05, –0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = −25.7) and those to dual regimen (ratio = −0.029, CD8 = +110.4).
Conclusions
We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained.
Journal Article