Bonferroni Method Research Articles

Analysis of the Changes and Possible Reasons in Aberrations before and after Surgery in Patients with Concomitant Exotropia.

Objective The objective is to observe the changes in aberrations before and after surgery in patients with common horizontal strabismus and to analyze the possible reasons for the changes. Methods Forty eyes of 40 cases with concomitant exotropia who underwent strabismus correction at the Ophthalmology Department of Nantong University Hospital from October 2020 to July 2021 were included in this study, all of whom underwent unilateral lateral rectus recession combined with a medial rectus resection in the same eye. Aberration parameters were measured 1 day before surgery and 1 week, 1 month, 3 months, and 6 months after surgery. Differences in the indicators at each time period were compared by analysis of variance (ANOVA) of repeated measures data for a single factor, and data were analyzed using SPSS 25.0 statistical application software. Results 5 mm pupil diameter: the preoperative and postoperative RMS of total aberration showed statistically significant difference (P < 0.01). Postoperation test (Bonferroni method) and preoperative comparison at each period after surgery showed statistically significant differences between 6 months after surgery (P=0.002) and preoperative comparison. The preoperative and postoperative comparison of RMS in LOAs was statistically significant (P < 0.01); postoperative test (Bonferroni method) and preoperative comparison showed that there were statistically significant differences between 1 week (P=0.033) and 6 months (P=0.002) after operation. The difference of RMS of defocus before and after operation was statistically significant (P < 0.01); postoperation test (Bonferroni method) and preoperative comparison showed that there was statistically significant difference between 6 months after operation (P=0.007) and preoperative comparison. There was statistically significant difference in preoperative and postoperative RMS of HOAs (P=0.013). Postoperative test (Bonferroni method) and preoperative comparison showed that there was statistically significant difference 6 months after surgery (P=0.03). The RMS of secondary astigmatism showed a statistically significant difference before and after operation (P=0.001), and the postoperation test (Bonferroni method) showed a statistically significant difference 6 months after operation (P=0.002). In 5 mm pupil diameter, the preoperative and postoperative RMS of total aberration showed statistically significant difference (P < 0.01), postoperative test (Bonferroni method) was used to compare each period after surgery with that before surgery, and there were statistically significant differences between 1 week after surgery (P=0.034), 3 months after surgery (P=0.033), and 6 months after surgery (P=0.003). The preoperative and postoperative comparison of RMS in LOAs was statistically significant (P < 0.01), postoperative test (Bonferroni method) was used to compare each period after surgery with that before surgery, and there were statistically significant differences between 1 week after surgery (P=0.04), 3 months after surgery (P=0.034), and 6 months after surgery (P=0.004). The difference of RMS of defocus before and after surgery was statistically significant (P=0.002), and the comparison between postoperation test (Bonferroni method) and preoperation showed that the difference was statistically significant 6 months after surgery (P=0.027). The RMS of astigmatism showed statistically significant difference before and after operation (P=0.002), and the postoperation test (Bonferroni method) showed statistically significant difference between 6 months after operation (P=0.009) and before operation. Conclusion We found that horizontal rectus surgery had a transient effect on LOAs and almost no effect on HOAs. Long-term follow-up is recommended after strabismus surgery to observe eye position and binocular visual function. Because of the high prevalence of strabismus in adolescents, long-term observation of the eye axis and aberration is recommended.

Four Weeks Of A Ketogenic Diet Increases Oxygen Consumption And Fat Oxidation During Moderate-intensity Walking

PURPOSE: Establish the time-course of changes in oxygen consumption, substrate metabolism, and heart rate during treadmill walking upon commencing a ketogenic diet. METHODS: In a randomized, parallel design, 53 men and women (mean ± SD, age: 35 ± 16 years, body mass index: 24 ± 3 kg/m2) were allocated to a moderate-sugar, moderate-carbohydrate diet [MODSUG; contribution of carbohydrate (of which sugars), fat and protein to total energy intake: 50% (15%), 35%, and 15%, respectively] a low-sugar, moderate-carbohydrate diet [LOWSUG; 50% (5%), 35%, and 15%, respectively] or a low-carbohydrate, ketogenic diet [LOWCHO; 8% (2%), 77%, and 15%, respectively] for 12 weeks. Oxygen consumption and substrate metabolism were determined by Douglas bags and heart rate using electrocardiography during submaximal walking at baseline, 4-weeks and 12-weeks of the dietary intervention. The submaximal treadmill test comprised 5-minute stages at 5.2 km/h with gradients of 0%, 3%, 6% and 9%. Data were analyzed by two-way (group x time) ANOVA with post-hoc test corrected for multiple comparisons by the Bonferroni method. RESULTS: Mean oxygen consumption rates displayed a group x time interaction (P = 0.016) whereby LOWCHO increased oxygen consumption from 17.8 ± 1.8 mL/kg/min at baseline to 18.4 ± 2.1 mL/kg/min by week 4 (P = 0.02), after which levels remained elevated at 18.4 ± 2.2 at week 12 (P > 0.05). Mean heart rate during all gradients increased with LOWCHO from 115 ± 12 beats/min at baseline to 121 ± 12 beats/min by week 4 (group x time interaction, P = 0.026; post-hoc comparison, P = 0.04), reaching 120 ± 14 beats/min at week 12 (P > 0.05). Peak fat oxidation rates increased with LOWCHO from 0.37 ± 0.18 g/min at baseline to 0.58 ± 0.25 g/min at week 4 with concomitant decreases in carbohydrate oxidation rates (group x time interaction, P < 0.001; post-hoc comparison, P < 0.001) with no further increases at week 12 (0.56 ± 0.27 g/min; P > 0.05). No such increases were observed with MODSUG or LOWSUG (all P > 0.05). CONCLUSIONS: Adaptations of oxygen consumption, heart rate and fat oxidation during walking plateau by 4 weeks of commencing a low-carbohydrate ketogenic diet, suggesting 4 weeks is sufficient to maximise metabolic adaptations to exercise with ketogenic diets. Supported by The Rank Prize Funds and Kenniscentrum Suiker & Voeding.

Evaluating the Mechanical Properties of Restorative Glass Ionomers Cements

The aim of this research was to assess the efficiency of 4 restorative glass ionomer cements (GICs): Fuji IX (GC), ChemFil Rock (DENSPLY), Riva Self-Cure (SDI), and Ketac Nano (3M ESPE). The 4 restorative glass ionomers' diametral tensile and compressive strengths were evaluated at room temperature for 24 hours and then stored in distilled water. The universal testing machine (INSTRON 5566A) was used to record the maximum load necessary to fracture specimens. Surface wear, diametral tensile strength, and compressive strength against dental ceramic were compared using analysis of variance followed by the Bonferroni method at a significance level of 0.05. Ketac Nano and ChemFil Rock were found to have better diametral tensile strength than Riva Self-Cure and Fuji IX. The significant difference between ChemFil Rock and Fuji IX (P ≤ .005) and ChemFil Rock with Riva Self-Cure (P ≤ .005) was shown by post hoc analysis. Ketac Nano had better tensile strength than Riva Self-Cure and Fuji IX. Fuji IX showed the lowest material loss of the GICs as revealed by wear against VITABLOCS Mark II (VITA Zahnfabrik). This study indicated a significant difference in the compressive strengths of ChemFil Rock and Riva Self-Cure. ChemFil Rock had the highest tensile strength. The diameter tensile strength of all 4 materials was statistically insignificant. Finally, Fuji IX had the least amount of material loss. ChemFil Rock was proven to be more effective than Fuji IX.

The value of 18F-NaF PET/CT in the diagnosis of bone metastases in patients with nasopharyngeal carcinoma using visual and quantitative analyses.

To assess the diagnostic value of 18F-NaF PET/CT in diagnosing bone metastases in patients with nasopharyngeal carcinoma (NPC) using visual and quantitative analyses. 164 patients with NPC who underwent 18F-NaF PET/CT between 2017 and 2021 were included. The sensitivity, specificity, and accuracy were calculated. All bone lesions were divided into metastatic bone lesion group and benign lesion group; the benign lesion group was further subdivided into benign lesion without osteophyte and fracture group (CT images showing no osteophyte, no fracture), and benign lesion with osteophyte and fracture group (CT images showing typical osteophytes and fractures), the differences in maximum standardized uptake value (SUVmax) were compared between every two groups, and the diagnostic cut-off values were derived from receiver operating characteristic curves (ROC). Quantitative data were expressed as mean ± SD, multiple continuous variables were compared using one-way analysis of variance (ANOVA), and multiple comparisons among more than two groups were made using the Bonferroni method. The sensitivity, specificity, and overall accuracy of 18F-NaF PET/CT for the diagnosis of bone metastases in NPC were 97.1%, 94.6%, and 95.1% based on the patient level and 99.5%, 91.5%, and 96.4% based on the lesion level, respectively. The SUVmax was significantly different between the metastatic bone lesion group and the benign lesion without osteophyte and fracture group (p < 0.05); the area under the curve was 0.865, the threshold was 12.5, the sensitivity was 0.912, and the specificity was 0.656. Visual analysis of 18F-NaF PET/CT has high sensitivity and specificity for diagnosing bone metastases in NPC. After excluding osteophytes and fracture lesions based on CT findings, using SUVmax ≥12.5 as the threshold can be an important reference for the differential diagnosis of bone metastases and benign bone lesions in patients with NPC.

Improving the diagnostic accuracy of apical hypertrophic cardiomyopathy using machine learning

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Hughes is supported by the British Heart Foundation (grant number FS/17/82/33222). Introduction The imaging criteria for diagnosis of apical hypertrophic cardiomyopathy (ApHCM) is a maximum wall thickness (MWT) ≥15mm. CMR enables detection of subtle phenotypic features (e.g. loss of apical tapering, cavity obliteration) and coupled with characteristic electrocardiogram changes, ApHCM can be diagnosed without overt hypertrophy. However, these patients are not captured by current diagnostic criteria. Purpose We sought to use a machine learning tool to quantify wall thickness and identify patients with ‘relative’ ApHCM that do not reach current diagnostic thresholds. Methods CMR images from 4118 healthy participants from the UK Biobank were segmented automatically with a clinically validated machine learning algorithm and wall thickness measured at all point in the myocardium by solving a solution to Laplace’s equation. MWT were pooled into 16 AHA segments and indexed to body surface area (BSA). The non-indexed and indexed segmental upper limit of normal was calculated as the mean + 3 standard deviations (the equivalent of 95% confidence interval after correcting for multiple [16] comparisons using the Bonferroni method). Results 73 overt ApHCM subjects (MWT&amp;gt;15mm) and 31 relative ApHCM subjects underwent CMR scanning. In healthy controls, the non-indexed (and indexed) upper limits were calculated for the apical-anterior 10.2mm (5.2 mm/m2), apical-septal 11.1mm (5.6 mm/m2), apical-inferior 10.5mm (5.3 mm/m2) and apical-lateral 10.1mm (5.2 mm/m2) segments. With a non-indexed cut-off, all (73 of 73) overt ApHCM and 84% (26 of 31) relative ApHCM were classified as having an abnormally thick apex. 3% (127 of 4118) of the healthy UK Biobank cohort were classified as abnormal, as expected. Using an indexed cut-off, all overt ApHCM and 87% (27/31) relative ApHCM were classified as abnormal, and 3% (123 of 4118) of the healthy UK Biobank cohort were misclassified. Conclusion We can successfully classify 87% of relative ApHCM patients from a normative reference range derived from a large cohort of healthy patients – a significant improvement on existing methods. We show that the specificity and sensitivity is increased when MWT is indexed to BSA. For practical clinical application, we recommend a cut-off of 10mm or an indexed cut-off of 5mm/m2 in any apical segment to diagnose apical LVH. Overt and relative apical HCM examplesHealthy controls AHA maps (non-indexed)

Body mass index related to executive function and hippocampal subregion volume in subjective cognitive decline.

ObjectiveThis study aims to explore whether body mass index (BMI) level affects the executive function and hippocampal subregion volume of subjective cognitive decline (SCD).Materials and methodsA total of 111 participants were included in the analysis, including SCD (38 of normal BMI, 27 of overweight and obesity) and normal cognitive control (NC) (29 of normal BMI, 17 of overweight and obesity). All subjects underwent the Chinese version of the Stroop Color-Word Test (SCWT) to measure the executive function and a high-resolution 3D T1 structural image acquisition. Two-way ANOVA was used to examine the differences in executive function and gray matter volume in hippocampal subregions under different BMI levels between the SCD and NC.ResultThe subdimensions of executive function in which different BMI levels interact with SCD and NC include inhibition control function [SCWT C-B reaction time(s): F(1,104) = 5.732, p = 0.018], and the hippocampal subregion volume of CA1 [F(1,99) = 8.607, p = 0.004], hippocampal tail [F(1,99) = 4.077, p = 0.046], and molecular layer [F(1,99) = 6.309, p = 0.014]. After correction by Bonferroni method, the population × BMI interaction only had a significant effect on the CA1 (p = 0.004). Further analysis found that the SCWT C-B reaction time of SCD was significantly longer than NC no matter whether it is at the normal BMI level [F(1,104) = 4.325, p = 0.040] or the high BMI level [F(1,104) = 21.530, p < 0.001], and the inhibitory control function of SCD was worse than that of NC. In the normal BMI group, gray matter volume in the hippocampal subregion (CA1) of SCD was significantly smaller than that of NC [F(1,99) = 4.938, p = 0.029]. For patients with SCD, the high BMI group had worse inhibitory control function [F(1,104) = 13.499, p < 0.001] and greater CA1 volume compared with the normal BMI group [F(1,99) = 7.619, p = 0.007].ConclusionThe BMI level is related to the inhibition control function and the gray matter volume of CA1 subregion in SCD. Overweight seems to increase the gray matter volume of CA1 in the elderly with SCD, but it is not enough to compensate for the damage to executive function caused by the disease. These data provide new insights into the relationship between BMI level and executive function of SCD from the perspective of imaging.

Short-Term Motor Outcomes in Parkinson's Disease after Subthalamic Nucleus Deep Brain Stimulation Combined with Post-Operative Rehabilitation: A Pre-Post Comparison Study.

Background The effects of subthalamic nuclear deep brain stimulation therapy (STN-DBS) and combined postoperative rehabilitation for patients with Parkinson's disease with postural instability have yet to be well reported. This study investigated the effects of short-term postoperative rehabilitation with STN-DBS on physical function in patients with Parkinson's disease. Methods Patients diagnosed with Parkinson's disease who were admitted to our hospital for STN-DBS surgery were included in this study. Data were prospectively collected and retrospectively analyzed. Postoperative rehabilitation consisted of muscle-strengthening exercises, stretching, and balance exercises for 40–60 minutes per day for approximately 14 days. The Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go test (TUG) seconds and steps, Trunk Impairment Scale (TIS), seconds for 10 times toe-tapping, lower limb extension torque using StrengthErgo240, and center of pressure sway in the quiet standing posture were evaluated preoperatively, postoperatively, and at discharge. Mini-BESTest changes were also evaluated in the two groups classified by the presence or absence of postural instability. One-way and two-way repeated measures analyses of variance were performed for each of the three periods of change, and paired t-tests with the Bonferroni method were performed as multiple comparison tests. A stepwise multiple regression model was used to identify factors associated with balance improvement. Results A total of 60 patients with Parkinson's disease were included, and there were significant increases in Mini-BESTest, TIS, StrengthErgo240, and postural sway during closed-eye standing compared to pre- and postoperative conditions at discharge (p < 0.05), and they decreased significantly compared to the postoperative period (p < 0.05). On stepwise multiple regression analysis, decreased steps of TUG and improvement of TIS scores were related to improvement of the Mini-BESTest (p < 0.05). In addition, Mini-BESTest scores in both groups with and without postural instability were significantly increased at discharge compared to preoperative and postoperative conditions (p < 0.01). Conclusion Postoperative rehabilitation combined with STN-DBS may provide short-term improvements in physical function compared with the preoperative medicated status. The improvements in gait step length and trunk function may be important factors for obtaining improvement of postoperative postural stability.

가상현실을 이용한 공간지각훈련이 성인의 뇌 기능과 하지의 근 활성도 및 균형능력에 미치는 영향

Purpose: The purpose of this study is to compare and analyze the effects on brain function, muscle activity, and balance ability after applying acute training of VR, VRT, and TE.BR Method: The subjects of the study were healthy male adults, who were fully informed about the purpose and method of this study and voluntarily expressed their intention to participate (N=20). The same subjects were applied for each training. The subjects were trained for 60 minutes each time at 1 week intervals. Measurement variables were brain function (fp1, fp2, T4, T5, pZ), muscle activity and balance ability (static balance and dynamic balance). All statistics were analyzed by SPSS version 25.0. A one-way repeated ANOVA was performed to confirm the difference in muscle activity during exercise according to the type of training, and the Bonferroni method was used for prost-hoc analysis. On the other hand, a two-way repeated ANOVA was conducted to verify the difference between EEG before and after training application. A paired t-test was performed to confirm the difference between before and after the applied exercise method. All statistical significance levels were set at p.05.BR Results: The results of this study are as follows. 1) VR and VRT showed statistically significant changes between times and, according to post-hoc test, VR and VRT showed a positive effect compared to TE. 2) The muscle activity of the lower extremities showed statistically significant changes in the right and left tibialis anterior, biceps femoris and gastrocnemius in TE. 3) The balance ability in both static and dynamic balance was not significantly different.BR Conclusion: In summary, the findings in this study confirm that VT and VTR have a positive effect on brain function. It can be recommended for new training.

Dissecting causal relationships between nonalcoholic fatty liver disease proxied by chronically elevated alanine transaminase levels and 34 extrahepatic diseases

BackgroundNonalcoholic fatty liver disease (NAFLD) is prevalent worldwide and is associated with the risk of many extrahepatic diseases. However, whether NAFLD is a risk marker or a common cause of extrahepatic diseases is unclear. MethodsWe searched PubMed to identify NAFLD-related extrahepatic diseases. Genetic instrumental variables (IVs) for NAFLD surrogated by chronically elevated alanine transaminase levels and eligible extrahepatic diseases were retrieved from the corresponding genome-wide association analysis. We proposed a procedure for Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and extrahepatic diseases. The Bonferroni method was used to correct the bias of multiple testing. ResultsIn total, 34 extrahepatic diseases were included and 54 SNPs were used as IVs for NAFLD. The MR analysis gave a robust and significant (or suggestive) estimate for the association between NAFLD and 9 extrahepatic diseases: type 2 diabetes (odds ratio [OR] = 1.182, 95 % confidence interval [CI] 1.125–1.243, P = 5.40 × 10−11), cholelithiasis (OR = 1.171, 95%CI 1.083–1.266, P = 7.47 × 10−5), diabetic hypoglycemia (OR = 1.170, 95%CI 1.071–1.279, P = 5.14 × 10−4), myocardial infarction (OR = 1.122, 95%CI 1.057–1.190, P = 1.46 × 10−4), hypertension (OR = 1.060, 95%CI 1.029–1.093, P = 1.18 × 10−4), coronary artery disease (OR = 1.052, 95%CI 1.010–1.097, P = 1.58 × 10−2), heart failure (OR = 1.047, 95%CI 1.006–1.090, P = 2.44 × 10−2), dementia (OR = 0.881, 95%CI 0.806–0.962, P = 5.01 × 10−3), and pancreatic cancer (OR = 0.802, 95%CI 0.654–0.983, P = 3.32 × 10−2). Validation analyses using IVs from biopsy-confirmed and imaging-determined NAFLD reported similar results to the main analysis. For the remaining 25 outcomes, no significant or definitive association was yielded in MR analysis. ConclusionsGenetic evidence suggests putative causal relationships between NAFLD and a set of extrahepatic diseases, indicating that NAFLD deserves high priority in clinical practice.

Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term secondary lifestyle behavioural outcomes.

Ashkenazi-Jewish (AJ) population-based BRCA testing is acceptable, cost-effective and amplifies primary prevention for breast & ovarian cancer. However, data describing lifestyle impact are lacking. We report long-term results of population-based BRCA testing on lifestyle behaviour and cancer risk perception. Two-arm randomised controlled trials (ISRCTN73338115, GCaPPS): (a) population-screening (PS); (b) family history (FH)/clinical criteria testing. North London AJ-population. AJ women/men >18 years. prior BRCA testing or first-degree relatives of BRCA-carriers. Participants were recruited through self-referral. All participants received informed pre-test genetic counselling. The intervention included genetic testing for three AJ BRCA-mutations: 185delAG(c.68_69delAG), 5382insC(c.5266dupC) and 6174delT(c.5946delT). This was undertaken for all participants in the PS arm and participants fulfilling FH/clinical criteria in the FH arm. Patients filled out customised/validated questionnaires at baseline/1-year/2-year/3-year follow-ups. Generalised linear-mixed models adjusted for covariates and appropriate contrast tests were used for between-group/within-group analysis of lifestyle and behavioural outcomes along with evaluating factors associated with these outcomes. Outcomes are adjusted for multiple testing (Bonferroni method), with P< 0.0039 considered significant. Lifestyle/behavioural outcomes at baseline/1-year/2-year/3-year follow-ups. 1034 participants were randomised to PS (n= 530) or FH (n= 504) arms. No significant difference was identified between PS- and FH-based BRCA testing approaches in terms of dietary fruit/vegetable/meat consumption, vitamin intake, alcohol quantity/ frequency, smoking behaviour (frequency/cessation), physical activity/exercise or routine breast mammogram screening behaviour, with outcomes not affected by BRCA test result. Cancer risk perception decreased with time following BRCA testing, with no difference between FH/PS approaches, and the perception of risk was lowest in BRCA-negative participants. Men consumed fewer fruits/vegetables/vitamins and more meat/alcohol than women (P< 0.001). Population-based and FH-based AJ BRCA testing have similar long-term lifestyle impacts on smoking, alcohol, dietary fruit/vegetable/meat/vitamin, exercise, breast screening participation and reduced cancer risk perception.

The impact of three critical success factors on online learning at the higher institutions

Globalization and rapid technological change have made knowledge a critical determinant of competitiveness in the world’s economy. Online education has been auspicious and adjustable even to students with tight schedules. However several critical success factors need to be improved in order to enhance the effective learner experience. This paper is aimed at uncovering the impact of three critical success factors namely; instructional design, learner interaction and learner technology adaptation on learner experience. Hence, the discretions of 300 students were diagnosed using the Likert scale questionnaire ranging from strongly agree to strongly disagree. The Holm Bonferroni method from R- package version 0.88 (2021 edition), was engaged to reduce the family-wise error (FWER) associated with multiple hypothesis comparison. It was observed that at a 5% level of significance, the alternative hypothesis was acceptable in favor of the null hypothesis and the conclusion was that instructional design, learner interaction, and technology adaptation, have a direct impact on the learning experience of the learner. The adopted models for the three critical success factors were validated by the Fornell and Larcker's (1981) convergent reliability test and tolerable with high composite reliability of 0.71. In accordance with the adopted model, a well instructional design is suggested for compliance.

Quantifying the Natural Variation of ‘Data Signatures’ from Aerosols Using Statistical Control Bands

The natural variation of the data signatures of airborne aerosols from calibrated cigarette particles were quantified using enhanced Bonferroni methods. The significance of the problem of improving analytical methods for understanding the natural variation of airborne particles cannot be understated given the positive impact for mitigating harmful airborne particles. The data presented in this paper were obtained using experiments to examine the effect of a carbon-brush-based bipolar ionization on filtration efficiency of a MERV 10 filter in a recirculating HVAC system. Ionization technology is deployed throughout the world as a multilayered approach with filtration for improving indoor air quality. Despite its wide use, ionization is still considered an emerging technology due to a dearth of peer-reviewed literature. Poorly designed test protocols and a lack of robust statistical methods for analyzing experimental data are the primary reasons. Presented herein is a statistical groundwork for analyzing ionization-efficacy data from highly controlled and properly designed particulate-matter test trials. Results are presented for three experimental groups where bipolar ionization was used to study the behaviors of data signatures from cigarette-smoke aerosol particles ranging in size from 49.6 to 201.7 nm. Statistical control bands of the data from these experimental groups revealed that bipolar ionization had significant changes to the pdfs and reductions in the natural variation of the data signatures for the particle count (number of particles) across all particle sizes. Statistical control bands may provide enhanced quantitative knowledge of variation and provide expanded inference that goes beyond examination of percentiles only. The implications from this research are profound, as it lays the groundwork for the development of highly effective ionization-filtration layered strategies to mitigate the hazards of airborne particulates and is the first step towards creating robust efficacy test standards for the industry.

IL-10 and TNFα are associated with decreased survival in low-risk pediatric acute myeloid leukemia; a children’s oncology group report

Pediatric acute myeloid leukemia (AML) is a devastating disease with a high risk of relapse. Current risk classification designates patients as high or low risk (LR) based on molecular features and therapy response. However, 30% of LR patients still suffer relapse, indicating a need for improvement in risk stratification. Cytokine levels, such as IL-6 and IL-10, have been shown to be prognostic in adult AML but have not been well studied in children. Previously, we reported elevated IL-6 levels in pediatric AML bone marrow to be associated with inferior prognosis. Here, we expanded our investigation to assess cytokine levels in diagnostic peripheral blood plasma (PBP) of pediatric AML patients and determined correlation with outcome. Diagnostic PBP was obtained from 80 patients with LR AML enrolled on the Children’s Oncology Group AAML1031 study and normal PBP from 11 controls. Cytokine levels were measured and correlation with clinical outcome was assessed. IL-6, TNFα, MIP-3a, and IL-1β were significantly higher in AML patients versus controls when corrected by the Bonferroni method. Furthermore, elevated TNFα and IL-10 were significantly associated with inferior outcomes. Our data demonstrate that in diagnostic PBP of LR pediatric AML patients, certain cytokine levels are elevated as compared to healthy controls and that elevated TNFα and IL-10 are associated with inferior outcomes, supporting the idea that an abnormal inflammatory state may predict poor outcomes. Studies are needed to determine the mechanisms by which these cytokines impact survival, and to further evaluate their use as prognostic biomarkers in pediatric AML.

Confirmatory efficacy testing for individual dose-placebo comparisons using serial gatekeeping procedure in dose-finding trials with multiple comparison procedures-modeling.

Dose-finding trials play a key role in the entire drug development process to determine optimal doses for regulatory approval. We address confirmatory efficacy testing for individual dose-placebo comparisons in the context of a dose-finding trial designed with multiple comparison procedures-modeling (MCP-Mod). An extension of the MCP-Mod, called closed MCP-Mod, has been proposed to carry out the MCP-Mod in conjunction with pairwise dose-placebo comparisons; however, an issue associated with the misspecification of candidate dose-response models remains. We consider another way to combine the MCP-Mod and the individual dose-placebo comparisons using serial gatekeeping procedures with fixed sequence, Holm, Hochberg, and step-down Dunnett procedure. The method controls the family-wise error rate in the strong sense and is simple enough to be implemented by existing software. Simulation studies suggested that the serial gatekeeping procedure was comparable with the closed MCP-Mod in terms of statistical power to detect the efficacy of at least one dose, and both methods were capable of pursuing the efficacy claim rather than just establishing the dose-response signal with less than a 20% increase in sample size when assuming monotonic dose-response shapes. The serial gatekeeping procedure would have advantages in the simplicity of implementation and ease of interpretation. The dose-finding trials aiming to declare the dose-response signal, as well as the efficacy of individual doses, would be worth considering as an option to accelerate the drug development program in certain situations.

A Preliminary Study of Proinflammatory Cytokines and Depression Following West Nile Virus Infection.

West Nile virus (WNV) is a neurotropic flavivirus that can cause acute febrile illness leading to neuroinvasive disease. Depression is a well-described outcome following infection, but the underlying pathogenic mechanisms are unknown. Proinflammatory cytokines play important roles in WNV infection, but their role in depression post-WNV remains unstudied. This research aimed to retrospectively evaluate associations between proinflammatory cytokines and new onset depression in a WNV cohort. Participants with asymptomatic WNV infection were significantly less likely to report new onset depression when compared to those with symptomatic disease. Participants with encephalitis and obesity were significantly more likely to report new onset depression post-infection. Based on univariate analysis of 15 antiviral or proinflammatory cytokines, depression was associated with elevated MCP-1 and decreased TNFα, whereas G-CSF was significantly elevated in those with a history of neuroinvasive WNV. However, no cytokines were statistically significant after adjusting for multiple comparisons using the Bonferroni method. While symptomatic WNV infection, encephalitis, and obesity were associated with new onset depression following infection, the role of proinflammatory cytokines requires additional studies. Further research involving paired acute-convalescent samples, larger sample sizes, and additional data points would provide additional insight into the impact of the inflammatory response on WNV-mediated depression.

Income Disparity and Mental Wellbeing among Adults in Semi-Urban and Rural Areas in Malaysia: The Mediating Role of Social Capital.

Mental illness is rising worldwide and is more prevalent among the older population. Among others, socioeconomic status, particularly income, has a bearing on the prevalence of mental health. However, little is known about the underlying mechanism that explains the association between income and mental health. Hence, this study seeks to examine the mediating effect of social capital on the association between income and mental illness. Cross-sectional data consisting of 6651 respondents aged 55 years and above were used in this study. A validated tool known as the Depression, Anxiety and Stress Scale, 21 items (DASS-21) was applied to examine mental illness, namely depression, anxiety, and stress. The Karlson, Holm, and Breen (KHB) method was employed to assess the intervening role of social capital on the association between income and mental illness. Results showed that those who disagreed in trust within the community had the highest partial mediation percentage. Those who disagreed in reciprocity, however, had the lowest partial mediation percentage, which explained the positive association between the middle 40% (M40) of the income group and depression, anxiety, and stress. Overall, the study suggests the need to increase trust and attachment within society to curb the occurrence of depression and anxiety.

0356 Does Unconscious Socioeconomic Bias Influence Tele-evaluation of Obstructive Sleep Apnea? A Tele-Equity Exploratory Analysis

Abstract Introduction Telemedicine, once of limited scope, has become common and widespread due to the present and ongoing SARS-CoV-2 pandemic. Center to home delivery, the most common model, allows for convenient and efficient care. Concurrent with this groundshift, there is increasing attention to disparities in medical services, and how these disparities may impact patient outcomes. Telemedicine could be used to help bridge barriers to timely quality care, however, patient access and longstanding institutional biases may limit the potential. Healthcare providers must actively develop systems to ensure that telemedicine is optimized for people across the income spectrum. This exploratory analysis examined how economic disparities in patients being evaluated for obstructive sleep apnea may be associated with providers’ clinical impressions. The objective was to study the inter-method reliability of pre-test probability of obstructive sleep apnea assessed via telemedicine and in-person evaluations, and to compare that reliability between income classes. Methods This is a secondary analysis of a pre-pandemic interrater reliability study, conducted between March 2017 and January 2019. Our researchers completed a randomized, blinded study comparing the pre-test probability of obstructive sleep apnea between an in-person physician and a separate physician seeing the same patient via televideo conferencing. Patients referred to the University of Rochester (UR) Sleep Center were eligible for the study. Women and men 30-70 years old were invited to participate. The patients were not necessarily referred to the center for evaluation of sleep disordered breathing. Patients with dementia, hearing or visual loss, severe psychiatric or developmental illness, or not fluent in English were excluded. Patients had adequate computer literacy, access to high speed internet, and a computing device with appropriate video camera and microphone.The primary objective of the original study was to assess the interrater reliability between the in-person and telemedicine raters for pre-test probability of sleep apnea (high, moderate, or low). Providers used clinical judgement from the history and examination to determine pre-test probabilityFor this present analysis, we assessed the inter-method reliability separately for strata defined by reported annual income level: low income (&amp;lt; $50,000), middle income ($50,000-$100,000), and high income (&amp;gt; $100,000). Reliability was quantified for each stratum using weighted kappa statistics given the ordinal nature of the outcome variable, pre-test probability of obstructive sleep apnea (high, moderate, or low). Weighted kappa statistics were compared between the income strata (high vs. middle, high vs. low, middle vs. low). The operant statistic assumed an approximate standard normal distribution under the null hypothesis of equal kappa values in the two income strata. The Bonferroni method was used to adjust the p-values for the three pairwise comparisons performed among the three income strata. Results Data from 53 patients were avaiable for this analysis. 11 of these patients were in the low income group, 22 in the middle income, and 16 were in the high income group. 9 patients did not include their income bracket, and were not included in the analysis. Inter-method reliabilities, assessed using weighted kappa, were 0.83 (low income), 0.24 (middle income), and 0.66 (high income). When comparing between the strata, the kappa statistics were significantly different (p=0.005) between the low and moderate income groups. There was a trend between the high and moderate income groups that did not meet statistical significance (p=0.07). Conclusion The intermethod reliability was substantial in the low income stratum, moderate in the high income stratum, and slight in the middle income group based on the kappa statistic. There was a significant difference in the reliability values of telemedicine versus in-person assessments between the low and middle income brackets, and there was a trend between the high and moderate groups. Since the raters were unaware of the patients’ income levels, this association might suggest possible unconscious bias in evaluating for OSA. It may also suggest that beyond access to telemedicine technology, the quality of the care may also be influenced by socioeconomic factors. With telemedicine in its early stages, it is important to develop this technology that will minimize biases that could result from patients’ economic fortunes. Support (If Any) The study was funded by a grant from the American Academy of Sleep Foundation (AASM Foundation grant #163-FP-17).

Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant.

BackgroundThe durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines.MethodsOne hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied.ResultsThe third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p < 0.001), 88% (p < 0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months.ConclusionsThe third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant.

Knowledge and Attitude about Infant Oral Health: A Paradox among Pregnant Women

To assess the knowledge and attitude of pregnant women about infant oral healthcare. A cross-sectional questionnaire study. A cross-sectional survey was conducted among 350 primigravida women aged between 20 and 40 years visiting the DY Patil Medical Hospital for their antenatal examination. A multiple-choice questionnaire with 12 questions in addition to demographic information and socioeconomic status was designed in three languages. Based on the level of education of the pregnant women, there was a statistically significant difference in knowledge and attitude toward infant oral healthcare (p = 0.001). The occupational status resounded significant differences between employed vs housewives and unemployed women (p = 0.000). Socioeconomic status also showed significant differences between the upper strata and lower strata groups (p = 0.000). Data normality was tested using the Kolmogorov-Smirnov test and Shapiro-Wilk test. Since the data were not normally distributed, we used nonparametric tests for analysis. The total scores for different domains were compared between the different subgroups based on age, occupation, education, trimester, and socioeconomic status using nonparametric one-way ANOVA (Kruskal-Wallis test). Post-hoc pairwise comparisons were done using Bonferroni's method. All testing was done using two-sided tests with alpha = 0.05 (95% confidence level). This study gives us an insight into the inadequacies existing in our society amongst expectant women in relation to oral health-promoting factors for infants. Educating pregnant women about maintaining their own oral health and care for their offspring will potentially help to curb early childhood dental diseases in future generations.

Effects of non-muscle myosin Ⅱ silenced bone marrow-derived mesenchymal stem cells transplantation on lung extracellular matrix in rats after endotoxin/lipopolysaccharide-induced acute lung injury

Effects of non-muscle myosin Ⅱ silenced bone marrow-derived mesenchymal stem cells transplantation on lung extracellular matrix in rats after endotoxin/lipopolysaccharide-induced acute lung injury