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Nevin Manimala Statistics

Analysis of incidence data in developmental toxicity studies: Statistical tests to account for litter effects in fetal defect data

Birth Defects Res. 2022 Nov 8. doi: 10.1002/bdr2.2120. Online ahead of print.

ABSTRACT

BACKGROUND: When analyzing fetal defect incidence in laboratory animal studies, correlation in responses within litters (i.e., litter effects) can lead to increased false-positive rates if litter effects are not incorporated into the analysis. Studies of fetal defects require analysis methods that are robust across a broad range of defect types, including those with zero or near-zero incidence rates in control groups.

METHODS: A simulation study compared power and false-positive rates for six approaches across a range of background defect rates and litter size distributions. Statistical methods evaluated included ignoring the litter effect as well as parametric and nonparametric approaches based on litter proportions, generalized linear mixed models (GLMMs), the Rao-Scott Cochran-Armitage (RSCA) trend test, and a modification to the RSCA (mRSCA) introduced here to improve estimation at low background rates. These methods were also applied to a common and a rare defect from two prenatal developmental toxicology studies conducted by the National Toxicology Program (NTP).

RESULTS: At background defect rates of 1%, the mRSCA and parametric litter proportion methods provided gains in power over the nonparametric litter proportion method, the GLMM method, and the RSCA method. Simulations involving litter loss in high-dose groups showed loss of power for both litter proportion methods.

CONCLUSIONS: The mRSCA test developed here compares favorably with other litter-based approaches and is robust across a range of background defect rates and litter size distributions, making it a practical choice for prenatal developmental toxicology studies involving both common and rare fetal defects.

PMID:36345811 | DOI:10.1002/bdr2.2120

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Nevin Manimala Statistics

Cerebrospinal Fluid Otorrhea After a Routine Tympanostomy Tube Placement: A Review of the Literature on Hyrtl Fissure

Ear Nose Throat J. 2022 Nov 8:1455613211039045. doi: 10.1177/01455613211039045. Online ahead of print.

ABSTRACT

OBJECTIVE: To review the literature on Hyrtl fissure (HF) and contribute our experience with a 2-year old who developed cerebrospinal fluid (CSF) otorrhea during routine tympanostomy tube placement.

METHODS: Data Sources: Pubmed and Google Scholar searches were conducted of articles in the English language literature from all time periods using the words Hyrtl, Hyrtl’s fissure, HF, and tympanomeningeal fissure. Study Selection: All relevant articles were reviewed to identify cases of HF.

RESULTS: Data Extraction: Nineteen cases, including ours, are described. Patient characteristics, method(s) of diagnosis and repair, and outcomes are reported. Computed tomography and intraoperative endoscopic images from our case are included. Presentation is more common in children (66.7% of cases where age was stated, n = 10) than in adults (33.3%, n = 5), and is most commonly unilateral (89.5%, n = 17). Cerebrospinal fluid otorrhea was the most common presentation. Six were discovered after tympanostomy tube placements while 3 were identified during cochlear implant work-up or after device failure. Surgical approaches described include endaural, transcanal, retrosigmoid, postauricular, and posterior fossa endoscopic. Multiple materials including bone wax, bone pate, fascia, muscle, and tissue sealant have been used. Our case describes an endoscopic repair in a child, which was successful at a 2-year follow-up. Data Synthesis: The small number of cases limits the utility of statistical analysis (n = 19).

CONCLUSIONS: Hyrtl fissure is a rare but important entity that may be discovered when routine procedures have unexpected results. Hyrtl fissure should be included in the differential diagnosis when there is persistent clear otorrhea after a tympanostomy tube, cochlear implant misinsertion, meningitis, or unexplained middle ear effusion in an adult.

PMID:36345799 | DOI:10.1177/01455613211039045

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Nevin Manimala Statistics

Uncollimated gamma camera measurements at two metres to the patient provide a practical and statistically robust method for SeHCAT retention calculation

Nucl Med Commun. 2022 Dec 1;43(12):1247-1253. doi: 10.1097/MNM.0000000000001626. Epub 2022 Oct 17.

ABSTRACT

[75Se]tauroselcholic acid (SeHCAT) retention studies may be performed using a collimated or uncollimated (intrinsic) gamma camera, with trade-offs between counting sensitivity, collision risk, and stray source influence. In this work, we evaluate the uncertainty in SeHCAT studies performed in ‘outer room’ mode, where the patient sits or stands two metres away from the uncollimated camera face. 768 SeHCAT studies performed at the Royal Free Hospital were analysed retrospectively, and in all cases, the absolute uncertainty was found to be well within the clinically acceptable limit of ±1 percentage point at 15% retention. The mean counting sensitivity was found to be 1.64 cps/kBq, which is higher than collimated counting but lower than uncollimated counting with the patient on the couch. Seeing as the outer room method does not require patients to transfer onto the couch it may provide savings in setup time which may offset the necessarily longer acquisition time. Because the patient does not come into close proximity to the unprotected camera face the risk of collision is also reduced. Spectra from a SeHCAT capsule in a water-filled torso phantom were used to examine the potential impact of modifying the energy windows. We recommend adopting a wide central photopeak and downscatter window (160-296 keV) plus a lower photopeak window (111-159 keV), which may provide significant improvements in sensitivity. This improved sensitivity could be used to reduce the acquisition time, which is of particular interest in the context of increasing numbers of referrals for SeHCAT retention tests.

PMID:36345770 | DOI:10.1097/MNM.0000000000001626

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Nevin Manimala Statistics

Bone metastases in prostate cancer – Gallium-68-labeled prostate-specific membrane antigen or Fluorine 18 sodium fluoride PET/computed tomography – the better tracer?

Nucl Med Commun. 2022 Dec 1;43(12):1225-1232. doi: 10.1097/MNM.0000000000001621. Epub 2022 Oct 19.

ABSTRACT

OBJECTIVE: The objective was to assess the roles of 68Ga-PSMA PET/CT and 18F-NaF PET/CT in evaluation of skeletal metastatic lesions in prostate cancer.

METHODS: Two hundred consecutive prostate cancer patients who had undergone 68Ga-PSMA PET/CT and 18F-NaF PET/CT at baseline evaluation (n = 80) and following suspected recurrence or disease progression (restaging) (n = 120) were analyzed retrospectively.

RESULTS: PSMA and NAF scans were positive for skeletal metastatic lesions in 67% (134 patients) and negative in 33% (66 patients). The scans were concordant in 80% (160 patients: 66 negative and 94 positive) and discordant in 20% (40 patients). Among 40 discordant results, 14 were baseline and 26 were restaging studies. PSMA detected more number of lesions in 11 (nine baseline and two restaging). These were true positive marrow or lytic metastatic lesions. NaF revealed more number of lesions in 29 (5 initial and 24 restaging). These were false positive on follow-up imaging. No statistical difference (P value = 0.7 by McNemar test) between the two scans for identifying absence or presence of at least one skeletal lesion was noted at baseline staging.

CONCLUSION: Though, both 18F-NaF and 68Ga-PSMA are excellent tracers for evaluation of skeletal metastases in prostate cancer, there is a distinct advantage of 68Ga-PSMA PET/CT due to detection of additional skeletal lesions and absence of false positive lesions. In addition, absence of PSMA avidity in healed metastases in the restaging setting opens up new avenue for assessment of response of skeletal metastases.

PMID:36345767 | DOI:10.1097/MNM.0000000000001621

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Nevin Manimala Statistics

Comparison of maximum and mean standardized uptake values of jaw pathologies with bone SPECT/CT: an especial focus on medication-related osteonecrosis of the jaw

Nucl Med Commun. 2022 Dec 1;43(12):1188-1194. doi: 10.1097/MNM.0000000000001624. Epub 2022 Oct 17.

ABSTRACT

OBJECTIVES: To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ).

METHODS: Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson’s correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance.

RESULTS: Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging.

CONCLUSION: The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ.

PMID:36345763 | DOI:10.1097/MNM.0000000000001624

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Nevin Manimala Statistics

Optimizing input parameter of the randomized singular value decomposition algorithm for compressing technetium-99m L,L, ethylenedicysteine renal dynamic study in minimum time preserving clinical information

Nucl Med Commun. 2022 Dec 1;43(12):1171-1180. doi: 10.1097/MNM.0000000000001618. Epub 2022 Oct 17.

ABSTRACT

OBJECTIVE: The SVDsketch [MATLAB function which implements a randomized singular value decomposition (rSVD) algorithm] uses tolerance (tol) to adaptively determine the rank of the matrix sketch approximation. As the tol gets larger, fewer features of input image matrix are used in the matrix sketch. The objective of this study was to optimize the value of tol for compressing technetium-99m (Tc-99m) L,L, ethylenedicysteine (LLEC) renal dynamic (RD) study in minimum time preserving clinical information.

MATERIALS AND METHODS: At different values of tol [0.00012(default), 0.1, 0.01, and 0.05] 50 Tc-99m LLEC RD studies were compressed. Two nuclear medicine (NM) physicians compared compressed images at tol = 0.1 with its input images. The SVD computation time and compression factor were calculated for each study. The image quality metrics: Error, structural similarity index for measuring image quality, brightness, global contrast factor (GCF), contrast per pixel (CPP), and blur were used for objective assessment of image quality. Percentage error in split function estimated from compressed and original images was calculated. Wilcoxon signed-rank test was applied to find statistically significant difference between renal split function, blur, GCF, CPP, and brightness of the compressed image and the original image at .

RESULTS: As per NM physicians, compressed images estimated with tol = 0.1 were identical to the original images. Based on image quality metrics, compressed images were significantly less noisy, brighter, and have better contrast compared with its input images. There was insignificant difference in split renal function estimated from compressed RD study at tol = 0.1 and its original study. The SVD computation and percentage compression per study were found to be 0.04725 s and up to 74.53%.

CONCLUSION: The optimized value of tol for compressing Tc-99m LLEC RD study preserving clinical information was found to be 0.1, and SVD computation time: 0.04725 s.

PMID:36345761 | DOI:10.1097/MNM.0000000000001618

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Nevin Manimala Statistics

Statistical analysis of hard X-ray radiation at the PAL-XFEL facility performed by Hanbury Brown and Twiss interferometry

J Synchrotron Radiat. 2022 Nov 1;29(Pt 6):1465-1479. doi: 10.1107/S1600577522008773. Epub 2022 Oct 7.

ABSTRACT

A Hanbury Brown and Twiss interferometry experiment based on second-order correlations was performed at the PAL-XFEL facility. The statistical properties of the X-ray radiation were studied within this experiment. Measurements were performed at the NCI beamline at 10 keV photon energy under various operation conditions: self-amplified spontaneous emission (SASE), SASE with a monochromator, and self-seeding regimes at 120 pC, 180 pC and 200 pC electron bunch charge. Statistical analysis showed short average pulse duration from 6 fs to 9 fs depending on the operational conditions. A high spatial degree of coherence of about 70-80% was determined in the spatial domain for the SASE beams with the monochromator and self-seeding regime of operation. The obtained values describe the statistical properties of the beams generated at the PAL-XFEL facility.

PMID:36345755 | DOI:10.1107/S1600577522008773

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Nevin Manimala Statistics

Megahertz-rate ultrafast X-ray scattering and holographic imaging at the European XFEL

J Synchrotron Radiat. 2022 Nov 1;29(Pt 6):1454-1464. doi: 10.1107/S1600577522008414. Epub 2022 Sep 29.

ABSTRACT

The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, results from the first megahertz-repetition-rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL are presented. The experimental capabilities that the SCS instrument offers, resulting from the operation at megahertz repetition rates and the availability of the novel DSSC 2D imaging detector, are illustrated. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative, providing an ideal test-bed for operation at megahertz rates. Our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range.

PMID:36345754 | DOI:10.1107/S1600577522008414

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Nevin Manimala Statistics

Characteristics and Outcomes of Sepsis Presenting in Inpatient Pediatric Settings

Hosp Pediatr. 2022 Nov 8:e2022006592. doi: 10.1542/hpeds.2022-006592. Online ahead of print.

ABSTRACT

OBJECTIVE: The pediatric sepsis literature lacks studies examining the inpatient setting, yet sepsis remains a leading cause of death in children’s hospitals. More information is needed about sepsis arising in patients already hospitalized to improve morbidity and mortality outcomes. This study describes the clinical characteristics, process measures, and outcomes of inpatient sepsis cases compared with emergency department (ED) sepsis cases within the Improving Pediatric Sepsis Outcomes data registry from 46 hospitals that care for children.

METHODS: This retrospective cohort study included Improving Pediatric Sepsis Outcomes sepsis cases from January 2017 to December 2019 with onset in inpatient or ED. We used descriptive statistics to compare inpatient and ED sepsis metrics and describe inpatient sepsis outcomes.

RESULTS: The cohort included 26 855 cases; 8.4% were inpatient and 91.6% were ED. Inpatient cases had higher sepsis-attributable mortality (2.0% vs 1.4%, P = .025), longer length of stay after sepsis recognition (9 vs 5 days, P <.001), more intensive care admissions (57.6% vs 54.1%, P = .002), and greater average vasopressor use (18.0% vs 13.6%, P <.001) compared with ED. In the inpatient cohort, >40% of cases had a time from arrival to recognition within 12 hours. In 21% of cases, this time was >96 hours. Improved adherence to sepsis treatment bundles over time was associated with improved 30-day sepsis-attributable mortality for inpatients with sepsis.

CONCLUSIONS: Inpatient sepsis cases had longer lengths of stay, more need for intensive care, and higher vasopressor use. Sepsis-attributable mortality was significantly higher in inpatient cases compared with ED cases and improved with improved sepsis bundle adherence.

PMID:36345706 | DOI:10.1542/hpeds.2022-006592

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Nevin Manimala Statistics

Child care and family processes: Bi-directional relations between child care quality, home environments, and maternal depression

Child Dev. 2022 Nov 8. doi: 10.1111/cdev.13858. Online ahead of print.

ABSTRACT

The current study examined whether within-family changes in child care quality and quantity predicted subsequent changes in home environment quality and maternal depression across early childhood (6 to 54 months of age). Data were drawn from the NICHD Study of Early Child Care and Youth Development (n = 1239; 77% White; 48% female; data collection from 1991 to 1996), and were analyzed using Random Intercept Cross-Lagged Panel Models. Within-family increases in child care quality predicted modest increases in home environment quality (β = .13-.17). These effects were most robust from child age 6 to 15 months. Increases in child care quality produced small, statistically non-significant, reductions in depression. Time-specific increases in child care quantity were not consistently predictive of either outcome.

PMID:36345701 | DOI:10.1111/cdev.13858