Exact P-value Research Articles

6471 Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone

Abstract Disclosure: N.I. Pollock: None. M. Song: None. A. Wolf: None. Y. Li: None. C. Hawkes: None. N. Motamedi: None. M.R. Denburg: None. S. Mostoufi-Moab: None. Title: Adult Height in Male Survivors of Childhood Cancer Treated with Aromatase Inhibitors and Growth Hormone Objectives: Aromatase inhibitor (AI) therapy in combination with growth hormone (GH), or as monotherapy, may have a role in improving height outcomes in male pediatric patients with GH deficiency (GHD). The effectiveness of AI therapy in the childhood cancer survivors is not known. In this retrospective study, we assess adult height (AH) in childhood cancer survivors treated with AI combined with GH therapy compared to those treated with GH alone. Methods: This was a single center retrospective cohort study of male survivors of childhood cancer treated with GH for diagnosis of GHD between 2007 and 2023. We compared AH outcomes in males treated with GH alone or in combination with off-label use of AI. Demographic and clinical characteristics, including anthropometric measurements, endocrinopathies, and cancer history, were obtained from the medical record. AH was noted as height documented at fusion of growth plates or following 18 years of age. Differences in demographic, clinical, and treatment characteristics were assessed using univariate tests of association. Multivariable regression with stepwise selection was used to examine risk factors associated with AH. All statistical analyses were performed using Stata 18.0. Results: Ninety-two patients were included; 70 were treated with GH monotherapy and 22 with combination AI/GH. Median age at AI initiation was 13.6 years (IQR 12.3-14.3) versus 11.2 years (IQR 8.6-12.9) for GH (unpaired t-test p-value <0.01; 95% CI -4.01, -1.91). A greater proportion of patients in the AI/GH group had been treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (Fisher’s exact p-value <0.01). There was no statistically significant difference in AH or AH Z-score between treatment groups, with the median AH Z-score in the AI/GH group -1.95 (IQR -3.11, -0.75) versus -1.39 (IQR -2.65, 0.11) in the GH group. In multivariable linear regression, history of radiation to the spine (β= -5.9, 95% CI -11.2, -0.6), height Z-score (β= 0.3, 95% CI 0.11, 0.46), BMI Z-score (β= 3.2, 95% CI 0.95, 5.5), and advanced bone age at GH or AI treatment initiation (β= -10.1, 95% CI -17.3, -2.9) were significantly associated with AH. Conclusions: Adjunctive treatment with AI and GH was not associated with increased AH outcomes in male survivors of childhood cancer compared to GH monotherapy. Future work is needed to determine optimal adjunctive medical therapy to maximize FAH impacted by cancer therapy for this patient population. Presentation: 6/3/2024

Classifying High-Frequency Oscillations by Morphologic Contrast to Background, With Surgical Outcome Correlates.

Ictal high-frequency oscillations (HFOs) are a reliable indicator of a seizure onset zone for intracranial EEG recordings. Interictal HFOs often are also observed and may be a useful biomarker to supplement ictal data, but distinguishing pathologic from physiologic HFOs continues to be a challenging task. We present a method of classifying HFOs based on morphologic contrast to the background. We retrospectively screened 31 consecutive patients who underwent intracranial recordings for epilepsy at Stanford Medical Center during a 2-year period, and 13 patients met the criteria for inclusion. Interictal EEG data were analyzed using an automated event detector followed by morphologic feature extraction and k-means clustering. Instead of only using event features, the algorithm also incorporated features of the background adjacent to the events. High-frequency oscillations with higher morphologic contrast to the background were labeled as pathologic, and "hotspots" with the most active pathologic HFOs were identified and compared with clinically determined seizure onset zones. Clustering with contrast features produced groups with better separation and more consistent boundaries. Eleven of the 13 patients proceeded to surgery, and patients whose hotspots matched seizure onset zones had better outcomes, with 4 out of 5 "match" patients having no disabling seizures at 1+ year postoperatively (Engel I or International League Against Epilepsy Class 1-2), while all "mismatch" patients continued to have disabling seizures (Fisher exact test P-value = 0.015). High-frequency oscillations with higher contrast to background more likely represent paroxysmal bursts of pathologic activity. Patients with HFO hotspots outside of identified seizure onset zones may not respond as well to surgery.

Effectiveness of Editing and Proofreading Skills in Improving Academic Writing of Law Students

Writing skills are the most difficult language skills for students, especially those students with English as a Second Language (ESL) and as an English Foreign Language (EFL) in various academic institutions. This situation has made most college students fail to write effective academic works. This study assessed the effectiveness of the Editing and Proofreading Skills Course in improving the academic writing of law students in Tanzania. Specifically, the study assessed the common errors made by law students in academic writing. The study involved the action research design consisting of pre- and post-interventions. Data were collected through observations and questionnaire methods. Data were analysed statistically through the Wilcoxon Signed-rank test and the McNemar exact test at 95% confidence intervals to analyse the before and after intervention data. The study found that law students had a limited basic understanding of the editing and proofreading techniques before the intervention. After the intervention, there was a significant improvement in students’ writing skills as the results showed an exact p-value of 0.000. It recommends the inclusion of specific instructions on Editing and Proofreading Skills Courses as part of the Legal Education Curriculum in Tanzania.

Abstracts of randomized controlled trials in splint therapy for temporomandibular disorders: Reporting quality and spin.

Poor reporting quality and spin in randomized controlled trial (RCT) abstracts can lead to misinterpretation and distorted interpretation of results. This methodological study aimed to assess the reporting quality and spin among RCT abstracts on splint therapy for temporomandibular disorders (TMD) and explore the association between spin and potentially related factors. The authors searched PubMed for RCTs on splint therapy for TMD. The reporting quality of each abstract was assessed using the original 16-item CONSORT for abstracts checklist. The authors evaluated the presence and characteristics of spin only in abstracts with nonsignificant primary outcomes according to pre-determined spin strategies. Logistic regression analyses were performed to identify factors associated with the presence of spin. A total of 148 abstracts were included in the reporting quality evaluation. The mean overall CONSORT score (OCS) was 5.86 (score range: 0-16). Only interventions, objectives and conclusions were adequately reported. Of the 61 RCT abstracts included for spin analysis, spin was identified in 38 abstracts (62.3%), among which 32 abstracts (52.3%) had spin in the Results section and 21 (34.4%) had spin in the Conclusions section. A significantly lower presence of spin was found in studies with exact p-value reporting (OR: 0.170; 95% CI: 0.032-0.887; p = .036) and a two-arm comparison design (OR: 11.777; 95% CI: 2.171-63.877; p = .004). The reporting quality of RCT abstracts on splint therapy for TMD is suboptimal and the prevalence of spin is high. More awareness and joint efforts are needed to improve reporting quality and minimize spin.

Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

BackgroundInfants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02).ResultsAn endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling.ConclusionsThis proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.

Sex- and age-related shift of relapse phenotypes in a cohort of relapsing multiple sclerosis patients: Post hoc analysis from the OPERA phase 3 trials.

Relapse presentation in relapsing multiple sclerosis (RMS) differs between sexes, leading to differential outcomes. An influence of age seems likely but is less well investigated separately for women and men. Using the large well-defined dataset of the pivotal trials of ocrelizumab in RMS, OPERA I and II, and their open-label extension, we performed a post hoc analysis to investigate relapse phenotypes for sex- and age-related differences in n = 929 relapses in 534 subjects (171 men, 363 women). Frequencies of affected functional systems were analyzed separated by sex and for three age strata (<35, 35-44, ≥45 years). Exact p-values are given for this exploratory analysis. Frequencies of mono- versus polysymptomatic relapse presentations were different neither between sexes nor in different age groups. Cerebellar symptoms were more frequent in relapses in men (female [f]: 23.1%, male [m]: 33.0%, p = 0.002), and women's relapses included more sensory (f: 53.8%, m: 32.3%, p < 0.001) and fatigue symptoms (f: 22.6%, m: 14.7%, p = 0.006). Whereas the sex difference for sensory involvement was present over all age groups (<35 years: f: 58.3%, m: 30.4%, p < 0.001; 35-44 years: f: 53.7%, m: 36.0%, p = 0.003; ≥45 years: f: 47.8%, m: 28.8%, p = 0.009), the difference for cerebellar involvement diminished with age (<35 years: f: 20.1%, m: 33.3%, p = 0.009; 35-44 years: f: 22.7%, m: 34.2%, p = 0.034; ≥45 years: f: 27.8%, m: 30.3%, p = 0.750). Relapse presentation seemed to shift with age in women only. We describe sex-specific relapse presentations and an influence of age only for women. Underlying causal factors warrant further investigations.

Saddlepoint p-values for a class of location-scale tests

ABSTRACT The main idea of this paper is to approximate the exact p-value of a class of non-parametric, two-sample location-scale tests. In this paper, the most famous non-parametric two-sample location-scale tests are formulated in a class of linear rank tests. The permutation distribution of this class is derived from a random allocation design. This allows us to approximate the exact p-value of the non-parametric two-sample location-scale tests of the considered class using the saddlepoint approximation method. The proposed method shows high accuracy in approximating the exact p-value compared to the normal approximation method. Moreover, the proposed method only requires a few calculations and time, as in the case of the simulated method. The procedures of the proposed method are clarified through four sets of real data that represent applications for a number of different fields. In addition, a simulation study compares the proposed method with the traditional methods to approximate the exact p-value of the specified class of the non-parametric two-sample location-scale tests.

Structural and functional cardiac parameters across occupations: a cross-sectional study in differing work environments

Previous investigations have highlighted notable variations in cardiovascular risk indicators associated with various professional categories. However, only a few studies have examined structural and functional cardiac parameters using echocardiography within distinct occupational groups. Hence, this study endeavored to assess cardiac structural and functional parameters in three additional occupations: firefighters (FFs), police officers (POs), and office workers (OWs). This prospective study encompassed 197 male participants (97 FFs, 54 POs, and 46 OWs) from Germany. All participants underwent 2D and Doppler echocardiography in resting conditions; standard parasternal and apical axis views were employed to evaluate structural (diastolic and systolic) and functional (systolic and diastolic function, and strain) cardiac parameters. All three occupational groups exhibited a tendency towards septal hypertrophy. Notably, OWs exhibited the largest diastolic interventricular septum diameter (IVSd), at 1.33 ± 0.25 cm. IVSd significantly varied between POs and OWs (p = 0.000) and between POs and FFs (p = 0.025). Additionally, during diastole a substantially larger left ventricular posterior wall diameter (LVPWd) was observed in OWs compared to FFs (p = 0.001) and POs (p = 0.013). The left ventricular diastolic cavity diameter (LVIDd) and the left ventricular systolic cavity diameter (LVIDs) were significantly higher in POs than they were in FFs (LVIDd: p = 0.001; LVIDs: p = 0.009), and the LVIDd was notably higher in FFs (p = 0.015) and POs compared to OWs (p = 0.000). FFs exhibited significantly better diastolic function, indicated by higher diastolic peak velocity ratios (MV E/A ratio) and E/E’ ratios, compared to POs (E/A ratio: p = 0.025; E/E’ ratio: p = 0.014). No significant difference in diastolic performance was found between OWs and FFs. Significantly higher E’(lateral) values were noted in POs compared to FFs (p = 0.003) and OWs (p = 0.004). Ejection fraction did not significantly differ among FFs, POs, and OWs (p > 0.6). The left ventricular mass (LV Mass) was notably higher in POs than it was in FFs (p = 0.039) and OWs (p = 0.033). Strain parameter differences were notably improved in two- (p = 0.006) and four-chamber (p = 0.018) views for FFs compared to POs. Concentric remodeling was the predominant change observed in all three occupational groups. Significant differences in the presence of various forms of hypertrophy were observed in FFs, POs, and OWs (exact Fisher test p-values: FFs vs. OWs = 0.021, POs vs. OWs = 0.002). OWs demonstrated notably higher rates of concentric remodeling than FFs did (71.77% vs. 47.9%). This study underscores disparities in both functional and structural parameters in diverse occupational groups. Larger prospective studies are warranted to investigate and delineate differences in structural and functional cardiac parameters across occupational groups, and to discern their associated effects and risks on the cardiovascular health of these distinct professional cohorts.

31 vs 35 mm: a randomized comparison of the pentaspline pulsed field ablation catheter sizes

Abstract Background Pulsed-Field ablation (PFA) is a non-thermal tissue-selective energy source which is increasingly used for pulmonary vein isolation (PVI). A commercially available pentaspline PFA catheter can be transformed between different configurations and is available in two different sizes – 31 and 35 mm of diameter. No clear recommendations for when to choose which catheter size are available to date. Purpose We aimed to assess procedural and outcome differences of the two different catheter sizes. Methods We prospectively included all-comer patients between 07/2022 and 01/2023 who had paroxysmal or persistent atrial fibrillation (AF) and were scheduled for PVI with PFA. There were no exclusion-criteria. 100 patients were randomly assigned to be ablated with either the 31 mm or the 35 mm pentaspline PFA catheter. Patients were routinely scheduled for follow-up visits 6 and 12 months after the ablation. Results Each group consisted of 50 patients and baseline characteristics were comparable. For the 31 mm vs 35 mm group respectively: Mean age 68.5 years vs 68.2 years, mean BMI 28.0 vs 30.3 kg/m², male sex 60% vs 68%, paroxysmal AF 59.6% vs 53.1%, mean LA diameter 40.9 vs 40.3 mm. Acute procedural efficacy defined as accomplishing PVI with the pentaspline PFA catheter was 100% in both groups. The procedural skin-to-skin time was numerically shorter in the 31 mm group (31.4 vs 34.3 minutes, p=0.11), which was attributed to a shorter ablation time (12.5 vs 15.1 minutes, p=0.052). Fluoroscopy time was significantly shorter (5.9 vs 7.1 minutes, p=0.015). The overall freedom of arrhythmia at 180 days was 82,1%. The groups show a numerical difference in freedom of arrhythmia (31 mm: 91,9% vs 35 mm: 73,4%), but no statistically significant difference using the log rank test (p=0.14, Figure 1). A total of 8 repeat procedures were performed in this patient collective for recurrent atrial arrhythmia - 3 in the 31 mm group, 5 in the 35 mm group. While the 3 repeat procedures in the 31 mm group showed no PV reconnections, 4 of the 5 patients in the 35 mm group had reconnected PVs (Fisher exact test p-Value=0.14). Overall, 25% (8/32) of PVs were reconnected, with the RSPV and RIPV being the most commonly reconnected veins (3 times each). Conclusion To the best of our knowledge, we provide the first randomized comparison of the two pentaspline PFA catheter sizes. Our data show longer procedure times and fluoroscopy times using the 35 mm device as well as a higher rate of PV reconnections especially at the septal PVs. Most importantly, we observe a trend towards worse clinical outcomes using the larger catheter. Longer follow-up times will be available at the time of presentation.Freedom from arrhythmia recurrence

Abstract PO3-11-12: A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study)

Abstract Background. Interventions to improve tolerability and adherence to endocrine therapy (ET) are critical to the global improvement of breast cancer (BC) survivorship. The optimal time of day to take ET in terms of quality of life, side effects and adherence is unknown. This study compared a morning dose versus an evening dose of ET in patients with early-stage BC (EBC). Methods. In this pragmatic, open-label, multicenter trial, patients with hormone receptor-positive (HR+) EBC were randomized (1:1) to receive either a morning dose (within 1 hour of the patient wake up time) or an evening dose of ET (within 1 hour of patient bedtime). The primary endpoint was endocrine toxicity/tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline (commencement of ET) to 12 weeks. The secondary endpoints included: ET toxicity/tolerability and quality of life (FACT-ES and FACT-B) from baseline to 4, 8, 12 and 52 weeks, non-persistence or non-adherence, and patient timing preference. Results. Between June 2021 and March 2022, 245 eligible patients were randomized, 122 to morning (122/245, 49.8%) and 123 to evening (123/245, 50.2%) dosing. Mean age was 61 [standard deviation (sd) 11.9], 181 patients (73.9%) were postmenopausal, 188 (76.7%) received tamoxifen, 58 (23.7%) received an aromatase inhibitor and 22 (9%) received luteinizing hormone-releasing hormone. The mean changes in the FACT-ES score from baseline to 12 weeks following the beginning of ET were -2.0 (sd=14.3) vs -5.4 (sd=16.8) in the morning vs evening arms respectively (Wilcoxon two-sample rank sum test p-value=0.22). Also, the proportion of patients with a clinically important increase (Fisher’s exact test p-value=0.54 0.89) or decrease (p-value= 0.89) in FACT-ES Scores was not statistically different between the arms. At 52 weeks, the mean changes in the FACT-ES score from baseline were -2.5 (sd=18.8) vs -4.8 (sd=15.5) in the morning vs evening arms respectively (p-value=0.23). There was no statistical difference in FACT-ES and FACT-B scores over the 52 weeks of the study. At 12 weeks, 94.5% (69/79) vs 98.7% (78/79) were still taking the ET (p-value=0.2), whereas at 52 weeks, 92.1% (58/63) vs 85.4% (41/48) were still taking ET (p-value=0.36), in the morning vs evening arms respectively. Also, 13.7% (10/73) vs 7.6% (6/79) and 3.2% (2/62) vs 12.5% (6/48) interrupted their ET at least once, in the morning vs evening arms, at 12 and 52 weeks respectively. At week 52, 57.9% (62/107) in the morning arm vs 13.5% (14/104) in the evening arm strongly preferred an ET morning dose, whereas 7.5% (8/107) vs 42.3% (44/104) strongly preferred an ET evening dose. No significant preference changes were observed in dose timing from baseline to week 52 (p-value=0.081). Conclusions. These results suggest no significant difference in quality of life or adherence if ET is taken in the morning or in the evening. Patients should be reassured that they can take ET at their preferred time. Clinical Trial Registration: NCT04864405 Table 1. Mean changes between FACT scores at 12 weeks and 52 weeks from baseline for patients receiving ET morning vs evening dose. A positive value indicates the FACT score increased over time. FACT ES: Endocrine Subscale; FACT B: breast Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Lesley Fallowfield, Terry Ng, Arif Awan, Sandeep Sehdev, Ana-Alicia Beltran-Bless, Mark Clemons. A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-12.

Exact p-values for global network alignments via combinatorial analysis of shared GO terms

Network alignment aims to uncover topologically similar regions in the protein–protein interaction (PPI) networks of two or more species under the assumption that topologically similar regions tend to perform similar functions. Although there exist a plethora of both network alignment algorithms and measures of topological similarity, currently no “gold standard” exists for evaluating how well either is able to uncover functionally similar regions. Here we propose a formal, mathematically and statistically rigorous method for evaluating the statistical significance of shared GO terms in a global, 1-to-1 alignment between two PPI networks. Given an alignment in which k aligned protein pairs share a particular GO term g, we use a combinatorial argument to precisely quantify the p-value of that alignment with respect to g compared to a random alignment. The p-value of the alignment with respect to all GO terms, including their inter-relationships, is approximated using the Empirical Brown’s Method. We note that, just as with BLAST’s p-values, this method is not designed to guide an alignment algorithm towards a solution; instead, just as with BLAST, an alignment is guided by a scoring matrix or function; the p-values herein are computed after the fact, providing independent feedback to the user on the biological quality of the alignment that was generated by optimizing the scoring function. Importantly, we demonstrate that among all GO-based measures of network alignments, ours is the only one that correlates with the precision of GO annotation predictions, paving the way for network alignment-based protein function prediction.

Abstract 6131: Increasing self efficacy, self confidence, and genetic knowledge via the Community Genetic Navigation Engagement Specialist Train-the-Trainer program

Abstract Background: Colorectal cancer (CRC) is the second and third leading cause of cancer deaths in US Hispanic/Latino (H/L) men and women, respectively. The Community Genetic Navigation Specialists (CoGENES) train-the-trainer program created a workforce of community health workers (CHWs) to educate H/L individuals about genetic testing, counseling, and research. Methods: The CoGENES three-week program, consisted of six in-person sessions, with a curriculum in both Spanish/English developed and delivered by experts, in Spanish, using presentations and hands-on activities. Acculturation, Latino values, self-efficacy, genetics and tumor testing knowledge, and self-confidence were assessed via pre- and post-training. Differences in scores were analyzed via Wilcoxon matched-pairs signed-rank tests with exact p-values. Results: Median age of the 12 participants was 50 (IQR = 12), 9 were female, 92% were Mexican-born, half completed 1-2 years of college, and 67% were very hispanic oriented. Self-efficacy increased after training, with pre- training median-score = 38.5 (IQR = 3) and post-training score = 39.5 (IQR =2.5) (p = 0.0547). Certainty about understanding tumor testing increased after training (p = 0.0039). The median number of correct answers on the 16-item genetic knowledge scale increased from 6.5 to 9.5 and the median number of “don’t know” responses decreased from 5 to 0 after training. Finally, self-confidence to train future CoGENES was significantly higher (p = 0.0098) at post-test. Conclusion: The CoGENES culturally tailored program led to improved self-efficacy, increased genetic knowledge, and self-confidence in a cohort of Hispanic community health educators. Findings will be shared within COPECC, and other NCI funded programs. Citation Format: Janet Rodriguez, Joel Sanchez Mendez, Yaneth L. Rodriguez, Lourdes Baezconde-Garbanati, Charité Ricker, Rosa Barahona, Bianca Rosales, Daisy Hernandez, Natalia Gutierrez, Julie Culver, Mariana Stern. Increasing self efficacy, self confidence, and genetic knowledge via the Community Genetic Navigation Engagement Specialist Train-the-Trainer program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6131.

Antisperm Antibody Levels After Vasectomy Reversal Are Not Associated With Pregnancy Rates or Method of Conception

ObjectiveTo examine the relationship between ASA, pregnancy rates, and method of conception following vasectomy reversal, given that before and after vasectomy reversal, patients wonder if antisperm antibodies (ASAs) will prevent them from achieving pregnancy and American Urological Association vasectomy guidelines call for additional research to answer this question. MethodsWe performed retrospective chart review and phone interview of patients who underwent vasectomy reversal at our institution from 1/1/2000 – 12/31/2018. We excluded patients who underwent vasectomy reversal for pain, or without postoperative semen analysis with ASA. We categorized patients as having low (<50%) or high (> 50%) ASA levels using the first postoperative semen analysis. Our primary outcome was pregnancy rate, including method of conception. Differences in pregnancy rates were tested using Fisher’s exact test. Results204 patients were chart reviewed. Median age at time of surgery was 40 years and median obstruction interval was 7.3 years. Median partner age was 32 years. 164 (80%) patients underwent bilateral vasovasostomy. 85 patients (42%) had low (<50%) ASA levels and 119 (58%) had high (≥ 50%) ASA levels.67 patients completed phone interviews. Of 27 men with low ASA levels, 19 (70%) achieved a pregnancy with 16 (59%) spontaneous pregnancy. Of 40 men with high ASA levels, 30 (75%) achieved a pregnancy with 16 (40%) spontaneous pregnancy. The Fisher’s exact test p-value was 0.2. ConclusionASA levels are not associated with pregnancy rate or method of conception after vasectomy reversal. These findings can improve patient counseling before and after vasectomy reversal.

Saddlepoint p-values for a class of location-scale tests under randomized block design

This paper deals with a class of nonparametric two-sample location-scale tests. The purpose of this paper is to approximate the exact p-value of the considered class under a randomized block design. The exact p-value of the considered class is approximated by the saddlepoint approximation method, also by the traditional method which is the normal approximation method. The saddlepoint approximation method is more accurate than the normal approximation method in approximating the exact p-value, and does not take a lot of time like the simulation method. This accuracy is proved by applying the mentioned methods to two real data sets and a simulation study.

The distribution of allele frequencies of the 15 Short Tandem Repeats loci in Elaziğ population, Türkiye

The DNA within the Human Genome involves loci with high polymorphism such as short tandem repeats (STR). The STR polymorphism analysis is extensively used for numerous purposes such as identification studies in forensic sciences, paternity tests, genome mapping, and population studies. In this study, blood and swab samples were obtained from 200 unrelated healthy individuals living in Elazig province. DNA was amplified via the AmpFlSTR Identifiler PCR Amplification Kit (Applied Biosystems, USA) to analyze the 15 STR loci. Using the ABI PRISM310 Genetic Analyzer capillary electrophoresis, the samples were analyzed and the allelic ladder was used to compare and identify the alleles of the samples, the distribution of the allele frequencies and peak values were examined. For statistical analysis Arlequin v.3.11 and PowerStats v.1.2 were used to assess the data. To determine if the allele frequencies were compatible with the Hardy-Weinberg (HW) equilibrium, the Markov chain and the Fisher's exact test p-value (p&lt;0.05) were examined. It was determined that the D8S1179 (0.00002), D21S11 (0.00593) and vWA (0.04939) loci were not compatible with the HW equilibrium, but the rest of the loci were compatible. For the loci, the combined power of exclusion is 0.9999995, the combined power of discrimination is 0.9999999999998. The probability of matching for the 15 STR loci was calculated to be 1 in 1.364x10ˉ17. The power of discrimination was quite high when all the loci were considered. The results of this study indicate that the populations residing in the Elaziğ province may benefit from paternity testing, forensic identification, and genomic mapping using the data as an appropriate marker.

The Associations of Cardiometabolic and Dietary Variables with Clinical Periodontitis in Adults with and without Type 2 Diabetes: A Cross-Sectional Study.

Periodontitis is a commonly occurring inflammatory oral disease affecting a large proportion of global and US adults and is characterized by the destruction of the tooth-supporting apparatus. Its etiology is multifactorial, and type 2 diabetes and diet play critical roles in its remission and progression. However, few studies have addressed nutritional and serum vitamin D status in adults with periodontitis in the presence of diabetes. A cross-sectional study (n = 78), and a sub-set of age- and BMI-matched case-control studies (n = 50), were conducted to examine differences in dietary and cardiometabolic variables, and serum vitamin D in adults with periodontitis with or without diabetes. Participants provided fasting blood samples and 24-h diet recalls on at least two different days. Data on health history, body weight, height, nutritional habits, and clinical features of periodontitis were also collected. The Mann-Whitney U Test (with exact p-value estimation by Monte Carlo simulation) was used to examine differences by diabetes status in continuous and ordinal variables. Results revealed significantly lower serum vitamin D, and dietary intake of fruits, vegetables, dairy, vitamins A and C in adults with periodontitis with vs. without diabetes in the sub-study (all p < 0.05). In the overall sample, adults with diabetes presented with higher caries risk measures and lower numbers of teeth than those without diabetes; plaque and bleeding scores did not differ by diabetes status. Finally, a significant associations of food habits was observed, especially consuming protein-rich foods twice a day with a lower bleeding score, and daily consumption of fried or fast foods with a fewer number of teeth present (all p < 0.05). The present findings show significant dietary and serum vitamin D inadequacies among adults with periodontitis, and diabetes further aggravates the observed malnourishment and oral health.

GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.

The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.

Cardiac function in patients with Paget disease of bone: standard and advanced echocardiographic study

Abstract Background/Introduction Paget’s disease of bone (PDB) is a common metabolic bone disorder and cardiovascular diseases are considered a possible PDB metabolic complication. Heart complications have only been described anecdotally as high-output heart failure due to high blood flow when skeletal involvement is extensive. Purpose Scientific studies that compare the structural and functional characteristics of the heart in this population are few and dated. The aims of this study were to evaluate echocardiographic parameters in PDB patients. Methods 60 PDB patients and 115 control subjects, matched by age, weight, height and history of arterial hypertension were enrolled. All subjects underwent to standard and advanced echocardiography examination. Results PBD patients showed a lower values of left ventricular ejection fraction (LVEF) (60,86 ± 4,51 vs 62,79 ± 4,30%, p 0,007), global longitudinal strain (GLS) (21,42 ± 2,20 vs 22,35 ± 2,21%, p 0,021) and myocardial work efficiency (MWE) (94,1 ± 2,0 vs 95,4 ± 2,9%, p 0,021), and higher values of interventricular septum thickness (IVSd) (9,9 ± 1,4 vs 9,1 ± 1,4 mm; p 0,003), and relative wall thickness (RWT) (0,38 ± 0,07 vs 0,35 ± 0,07, p 0,031) compared to controls, while there were no significant difference between the other parameters analyzed (Table 1). Calcification and/or sclerosis of aortic valve was detected in 26 PDB patients (43,3%) compared to 27 subjects (23,5%) in control group (Fisher’s exact test p-value = 0,006). Calcification and/or sclerosis of mitral annulus was detected in 14 PDB patients (23,3%) compared to 12 controls (11,6%) (Fisher’s exact test p-value = 0,022) (Table 2). Conclusion The study results support the hypothesis that PDB is a systemic condition, influencing cardiac function and structure, associated with increased cardiovascular risk. Our data showed that myocardial function in PDB patients is impaired. The lower resting values of LVEF, GLS and MWE represent an early subclinical myocardial damage.Table 1Table 2

Improving Patient Compliance with Vaginal Dilator Therapy by Implementation of Sexual Health Consult in Gynecologic Malignancies after Radiation Therapy

Typical vaginal dilator therapy (VDT) compliance falls short at approximately 30% of patients in reported studies, which could lead to vaginal stenosis (VS) in as high as 88% of patients who undergo radiation therapy (RT) for gynecologic malignancies. In an ongoing effort to improve adherence to VDT aimed to prevent vaginal stenosis post pelvic and vaginal RT, a prospective study was implemented to assess the feasibility and the impact on vaginal dilator therapy adherence when implementing a consult with the oncology women's sexual health clinic following the completion of radiation therapy. This was a single institution, prospective analysis and feasibility study that included patients diagnosed with a gynecologic cancer who were treated with RT to the pelvic and or vaginal tissues. Using purposive sampling, the treating radiation oncologists identified eligible patients and referred them to the oncology women's sexual health clinic for consult four to six weeks status post completion of RT in a six-month period. A post treatment survey was conducted via a telephone interview 12 weeks after the sexual health clinic initial consult to assess vaginal dilator therapy compliance. Descriptive statistics were calculated. Pre-intervention retrospective data analysis revealed poor compliance to VDT with only 3 of 40 (7.5%) patients judged as compliant. Post-intervention, 30 of 37 (81.1%) patients in the sample were judged compliant. The adherence rate in the post-intervention group was significantly higher (Fisher's Exact Test two-tailed p-value < 0.0001). With confidence of 95%, the proportion of the potential population that would adhere post intervention was between 68.5% and 93.7%. Sociodemographic and clinical characteristics did not have a statistically significant correlation with VDT compliance. Implementing a referral to an oncology women's sexual health clinic at the completion of RT for the sample population is feasible. Our project demonstrates that instituting this new sexual health clinic may have a large, positive impact on patient compliance to vaginal dilator therapy. More importantly, this may lead to decrease incidences of vaginal stenosis and improvement in patient health outcomes and quality of life (QoL).

Exact p-value calculation for XCorr scoring of high-resolution MS/MS data.

Exact p-value (XPV)-based methods for dot product-like score functions-such as the XCorr score implemented in Tide, SEQUEST, Comet or shared peak count-based scoring in MSGF+ and ASPV-provide a fairly good calibration for peptide-spectrum-match (PSM) scoring in database searching-based MS/MS spectrum data identification. Unfortunately, standard XPV methods, in practice, cannot handle high-resolution fragmentation data produced by state-of-the-art mass spectrometers because having smaller bins increases the number of fragment matches that are assigned to incorrect bins and scored improperly. In this article, we present an extension of the XPV method, called the high-resolution exact p-value (HR-XPV) method, which can be used to calibrate PSM scores of high-resolution MS/MS spectra obtained with dot product-like scoring such as the XCorr. The HR-XPV carries remainder masses throughout the fragmentation, allowing them to greatly increase the number of fragments that are properly assigned to the correct bin and, thus, taking advantage of high-resolution data. Using four mass spectrometry data sets, our experimental results demonstrate that HR-XPV produces well-calibrated scores, which in turn results in more trusted spectrum annotations at any false discovery rate level.