Proportion Of Pairs Research Articles

Random generation of the special linear group

It is well known that the proportion of pairs of elements of SL ⁡ ( n , q ) \operatorname {SL}(n,q) which generate the group tends to 1 1 as q n → ∞ q^n\to \infty . This was proved by Kantor and Lubotzky using the classification of finite simple groups. We give a proof of this theorem which does not depend on the classification. An essential step in our proof is an estimate for the average of ( ord ⁡ g ) − 1 (\operatorname {ord} g)^{-1} when g g ranges over GL ⁡ ( n , q ) \operatorname {GL} (n,q) , which may be of independent interest. We prove that this average is \[ exp ⁡ ( − ( 2 − o ( 1 ) ) n log ⁡ n log ⁡ q ) . \exp (-(2-o(1)) \sqrt {n \log n \log q}). \]

Comprehensive tumor profiling-guided therapy in rare or refractory solid cancer: A feasibility study in daily clinical practice

Tumor profiling has been shown to benefit patients with rare or refractory metastatic cancer, but several limitations hamper its use in daily clinical practice. We aim to assess the added benefit of a comprehensive tumor profiling, including factors predictive of response to targeted and cytotoxic therapy, in the treatment of refractory or rare solid tumors outside of a formal clinical trial. Patients were included between 2013 and 2017. Multiplatform comprehensive tumor profiling (CTP) was performed on FFPE specimens. Tumor response was evaluated by imaging using the RECIST criteria version 1.1. The PFS ratio was defined as PFS under CTP-guided therapy (PFS2)/PFS under previous standard therapy (PFS1). A clinical benefit was identified if the PFS ratio exceeded the 1.3 threshold value. In total, 184 patients were enrolled among whom 104 were evaluable for the PFS ratio. Objective response rates (ORR) were equal to 25% (CI95: 16.6-33.4%) and 36.5% (CI95: 27.2-45.8%) on the last therapy before CTP and on the CTP-guided therapy respectively (P-value=0.058 on paired proportion comparison test). The proportion of patients achieving a PFS2/PFS1 ratio≥1.3 was equal to 50%. The median PFS1 was statistically lower than PFS2 (120 days compared to 184 days respectively, P-value log rank 0.01). These results confirm the feasibility and the added benefit of a CTP in patients with refractory tumors in daily clinical practice especially in patients not able to enter a clinical trial.

Abstract P5-01-06: Cell-free DNA (cfDNA) analysis of ESR1-mutant advanced breast cancer (aBC): Impact of subsequent therapy on mutation persistence

Abstract Background: Acquired ESR1 mutations (ESR1MUT) are common resistance mechanisms in estrogen receptor positive (ER+) aBC following aromatase inhibitor (AI) therapy. ESR1MUT can be identified using plasma-based cfDNA testing in patients with progressive aBC and may be cleared (i.e. become undetectable) following response to effective therapeutic interventions. Optimal treatment for ESR1MUTaBC has not been established. We retrospectively examined the impact of various treatments on ESR1MUT detection among patients with aBC undergoing serial cfDNA testing. Methods: The deidentified Guardant Health database was queried for patients with aBC (stage IIIB/IV) with multiple cfDNA samples, at least one of which had an ESR1MUT detected (patients tested between March 2014-March 2019 using a 54-73 gene cfDNA next-generation sequencing panel, Guardant360™). Consecutive sample pairs were identified in which the first sample had ≥1 ESR1MUT and subsequent treatment could be determined from the test request form. For patients receiving combination therapy, each therapy was counted individually (e.g. a patient receiving a CDK4/6 inhibitor and an AI would be counted once for each). Each sample pair was classified as to whether any ESR1MUT persisted in the subsequent cfDNA sample. Additionally, the change in ESR1 variant allele fraction (αVAF) between the first and subsequent sample was calculated for each ESR1MUT identified. We considered ESR1MUT that had lower VAF on the subsequent sample (e.g. a negative αVAF) as evidence of a therapeutic response against ESR1MUT for the purpose of this study. The proportion of sample pairs in which the ESR1MUT was cleared, as well as the proportion of any ESR1MUT with decreased VAF was compared by treatment type using Fisher’s exact test. Results: A total of 262 ESR1 mutations were found in 167 unique sample pairs from 124 aBC patients. The median time between sample collection for each pair was 17 weeks (range: 0.7 - 133 weeks). ESR1MUT were cleared in a minority (30/167, 18%) of sample pairs with an overall minimal change in observed VAF (median αVAF of -0.01). A negative ESR1MUT VAF was observed for more than half of all ESR1MUT in patients receiving certain endocrine therapies, including fulvestrant, tamoxifen, and goserelin, and non-endocrine therapies, including chemotherapy, anti-HER2, and CDK4/6 inhibitors, suggesting these agents may still have some efficacy against ESR1MUT (Table 1). The proportion of sample pairs with ESR1MUT clearance was not significantly different for those on endocrine therapy versus those not on endocrine therapy (16% vs 19%). Similarly, there was no significant difference between these groups when examining the proportion of ESR1MUT with decreased VAF (50% vs 50%). Conclusions: In this exploratory analysis of serial cfDNA testing of ESR1MUTin aBC, some variation was observed in the efficacy of commonly used therapies as measured by the proportion of sample pairs with clearance of ESR1MUT and by the proportion of all ESR1MUT with a decreased VAF. We believe these data may be useful in guiding future analysis into optimal therapy for patients with ESR1MUTaBC. Notably, none of the therapies stood out as having promising efficacy against a large proportion of ESR1MUT subclones suggesting that additional therapeutic options may be needed to effectively target and provide long-term disease control of ESR1MUT aBC. Table 1. Temporal changes in ESR1MUT in cfDNA by therapy in aBCTreatmentNo. Sample PairsESR1MUT ClearedNo. ESR1MUTESR1MUT with VAF DecreaseMedian αVAFAI2520%3842%0.09SERD (Fulvestrant)3312%4553%-0.03Estrogen Receptor Agonist (Tamoxifen)30%667%-0.18GnRH Agonist (Goserelin)813%1464%-0.09Chemotherapy8319%13052%-0.09Anti-HER2229%2752%-0.02Everolimus2512%3749%0.05CDK4/6 Inhibitor3119%4953%-0.05Immune Checkpoint520%838%0.02Any Endocrine Therapy6316%9250%-0.01No Endocrine Therapy10419%17050%-0.01OVERALL16718%26250%-0.01 Citation Format: Caroline M. Weipert, Thereasa A. Rich, Rebecca J. Nagy, Sarah Croessmann, Ben H. Park, Joyce O'Shaughnessy, Mohammad Nezami, Massimo Cristofanilli, Aditya Bardia, Richard B. Lanman. Cell-free DNA (cfDNA) analysis of ESR1-mutant advanced breast cancer (aBC): Impact of subsequent therapy on mutation persistence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-06.

Feasibility and Health Benefits of an Individualized Physical Activity Intervention in Women With Metastatic Breast Cancer: Intervention Study.

BackgroundThere is limited knowledge regarding the potential benefits of physical activity in patients with metastatic breast cancer.ObjectiveThe Advanced stage Breast cancer and Lifestyle Exercise (ABLE) Trial aimed to assess the feasibility of a physical activity intervention in women with metastatic breast cancer and to explore the effects of physical activity on functional, psychological, and clinical parameters.MethodsThe ABLE Trial was a single-arm, 6-month intervention study with a home-based, unsupervised, and personalized walking program using an activity tracker. At baseline and 6 months, we assessed anthropometrics, functional fitness, physical activity level, sedentary behavior, quality of life, fatigue, and tumor progression. Paired proportions were compared using the McNemar test and changes of parameters during the intervention were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney test, and Spearman rank correlations.ResultsOverall, 49 participants (mean age 55 years; recruitment rate 94%) were enrolled and 96% adhered to the exercise prescription (attrition rate 2%). Statistically significant improvements in the 6-minute walking distance test (+7%, P<.001) and isometric quadriceps strength (+22%, P<.001), as well as decreases in body mass index (-2.5%, P=.03) and hip circumference (-4.0%, P<.001) were observed at 6 months. Quality of life remained stable and a nonstatistically significant decrease (-16%, P=.07) in fatigue was observed.ConclusionsThe high recruitment and adherence rates suggest the willingness of patients with metastatic breast cancer to participate in a physical activity program. The beneficial outcomes regarding physical fitness and anthropometry of this unsupervised physical activity program may encourage these patients to maintain a physically active lifestyle. Future randomized controlled trials with larger sample sizes are warranted.Trial RegistrationClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886

РЕЗУЛЬТАТИ ОБЛІКІВ ЛЕЛЕКИ БІЛОГО (CICONIA CICONIA L.) У НАЦІОНАЛЬНОМУ ПРИРОДНОМУ ПАРКУ "ПИРЯТИНСЬКИЙ" ТА НА ПРИЛЕГЛІЙ ТЕРИТОРІЇ

The monitoring of population state of White Stork (Ciconia ciconia L.) in the National Nature Park "Pyriatynskyi" and surrounding area was carried out in 2014–2019. The number of nests in the area was counted and the nest site selection were investigated. A breeding success analysis was also conducted. There were from 86 to 102 nests occupied by storks observed for a six-year study period. The mean number of fledglings in relation to all nest occupying breeding pairs (JZa) was 2,43 ± 0,04 (n = 570), and in relation to breeding pairs with nestlings (JZm) was 2,75 ± 0,04 (n = 502). The percentage of unsuccessful pairs was 10,07 % (%HPo). In different years, breeding success (the proportion of successful pairs with fledglings) ranged from 78,43 % in 2017 to 98,94 % in 2015. The majority of pairs fledged 2 (34,93 %) or 3 (36,92 %) young, that makes 71,85% of broods for total. Broods of 5 nestlings, which is the maximum value for the study area, are rare and registered not every year. Only 4,44% of the total number of such nests was identified for six years. During 2015–2016 storks hatched a smaller number of nestlings, but far more successfully fledged them than in the previous year 2014 and subsequent 2018–2019 years. The year 2017 became the most unfavorable for stork breeding in the region of the park – birds raised the smallest number of fledglings, and the proportion of unsuccessful pairs was the largest for the years of observation. All found nests of a White Stork are located singly within the boundaries of settlements. The preferred nest site is on poles (69,29 % of the total nest number), other types of placement are less common (trees, buildings of various types, water towers and artificial nests). 10 or more nests of storks were recorded in the villages Deimanivka, Povstyn, Antonivka, Usivka and Kaplyntsi located in the floodplain of the Udai river. The average density of nests per settlement was 1,7 ± 0,3 km2.

Validity of a questionnaire developed to measure the impact of a high-fidelity simulation intervention: A feasibility study.

To evaluate the validity and responsiveness of a questionnaire developed to measure the impact of a high-fidelity simulation intervention. A pre- and postintervention design. In August 2017, 107 participants completed a questionnaire measuring knowledge and perceived self-confidence pre- and postintervention. Validity of the questionnaire was determined by expert reviews, individual interviews and estimates of the changes in knowledge and perceived self-confidence. The changes were estimated by the differences between paired proportions of participants. The responsiveness of the ordered categorical item scores on self-confidence was evaluated by the measure of systematic group change and individual variations. The analysis of the interviews resulted in three themes: item content, item style and the administration of the questionnaire. An intervention effect on knowledge assessments was shown by the changes in paired proportions of participants with increased or decreased correct assessments (ranging from -25.5 - 24.8 percentage units). The responsiveness of the self-confidence scale was confirmed by evidence of post-intervention systematic group changes towards higher levels. This study provides useful experience for a forthcoming randomized controlled study to evaluate the effect of high-fidelity simulation on undergraduate nursing students' knowledge and self-confidence when assessing patient deterioration. Cause-and-effect relationship between simulation and learning is required to improve nursing education. A statistically significant rise in students' knowledge and levels of self-confidence after simulation were identified in this study. The study provided important aspects of future research study designs.

HIV Transmission Chains Exhibit Greater HLA-B Homogeneity Than Randomly Expected.

HIV's capacity to escape immune recognition by human leukocyte antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to the host HLA type and could better improve therapeutic strategies against HIV. Three hundred one to 325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA class I data were compiled at 3 specificity levels: 4-digit, 2-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as 2 measures: the proportion of transmission pairs, which are HLA concordant, and the average percentage of allele matches within all clusters. These measures were compared with the mean value across randomizations with randomly assorted individuals. We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by the risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs. 0.251, P value = 0.009; supertype clusters: 0.659 vs. 0.611, P value = 0.002; supertype pairs: 0.655 vs. 0.608, P value = 0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men but not for other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, although this yielded no significant pattern. The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.

A high concentration electrolyte enables superior cycleability and rate capability for high voltage dual graphite battery

Implementing reliable battery systems with long cycle life, high power output and low cost are of great importance. High performance dual-graphite battery (DGB) is one of promising candidates. Herein, we develop a novel high concentration electrolyte (HCE), 2 M LiPF6- ethyl-methyl carbonate/sulfolane, which can endow the DGB with a high ceiling voltage of 5.3 V, an elongated cycle life (94.7% of capacity retention after 1000 cycles at 5 C rate) and simultaneously fast charging/discharging kinetics (91.0 mAh g−1 even at 20 C rate). Combinational experiments are conducted to investigate the mechanism of this HCE on the improvement of the electrochemical performance. It is found that this HCE could suppress the graphite cathode from structural collapse owing to the increased proportion of contact ion pairs and ion aggregates. Besides, it prompts the formation of a dense and uniform SEI layer, leading to highly reversible Li+ intercalation/deintercalation. This would promote the development of DGB with high rate performance and excellent cycleability.

Validation of mother-infant linkage using Medicaid Case ID variable within the Medicaid Analytic eXtract (MAX) database.

The state-assigned Case ID number in the Medicaid Analytic eXtract (MAX) allows for potential linkage of mothers to infants. No validation of respective linkage algorithms is available. We established and validated an algorithm within MAX that links mothers to infants and to identify factors influencing successful mother-infant linkage. We identified all mother-infant pairs in FL and TX birth certificates records (BCR) that could be linked individually to MAX records (1999-2005 for FL and 1999-2010 for TX) based on Social Security Number (gold standard pairs). Case ID linkage performance was evaluated as the proportion of gold standard mother-infant pairs that were identified by the algorithm (sensitivity) and the proportion of algorithm defined mother-infant pairs that were correctly linked. Generalized estimating equations were used to calculate the probability for successful Case ID algorithm linkage versus non-linkage using maternal and infant characteristics. We identified 323,160 gold standard pairs in FL BCR and MAX and 1,025,350 in TX BCR and MAX. Depending on Medicaid enrollment the algorithm sensitivity ranged from 85.51% to 87.96% in FL and 19.60% to 35.75% in TX. In both states, positive predictive value exceeded 99%, regardless of enrollment periods. Determinants for successful linkage varied across states, but suggested better results for younger mothers, minority women, and those with lower educational achievement. Our algorithm can correctly link liveborn infants to their mothers. The algorithm's sensitivity in identifying pairs varied across states, but PPV was consistently high. Linkage performance was associated with certain characteristics that may affect representativeness of successfully linked pairs.

103-LB: Intergenerational Improvements of Continuous Glucose Monitoring Systems in Youth

Standard methods and metrics to describe the accuracy of continuous glucose monitoring (CGM) systems in children and adolescents are subject to change. We reanalyzed data from youth ages 6-17 from clinical trials evaluating G4 PLATINUM (NCT01667185), G5 Mobile (NCT02280577), and G6 (NCT02880267) CGM systems (all from Dexcom, Inc., San Diego, CA). Subjects participated in 1-2 clinic sessions of varying duration, depending on their age, throughout the 7-day wear of G4 and G5 and 10-day wear of G6 for comparison of CGM values with temporally matched YSI measurements. Reference measurements were obtained every 15±5 minutes and paired with the CGM measurement that immediately followed (within 5 minutes). Percent accuracy was defined as the proportion of CGM values within ±20% of paired YSI values for CGM values &amp;gt;100 mg/dL or within ±20 mg/dL of paired YSI values for CGM values ≤100 mg/dL. Accuracy was also evaluated using the mean absolute difference (MAD) and mean absolute relative difference (MARD) between CGM and YSI pairs, as well as the proportion of pairs in Clarke Error Grid (CEG) Zone A. Accuracy improved dramatically from G4 to G6, regardless of the metric evaluated (Table). Improved device performance may drive increased uptake and adherence, especially among children and adolescents. Disclosure S. Puhr: Employee; Self; Dexcom, Inc. P. Calhoun: Stock/Shareholder; Self; Dexcom, Inc. J. Welsh: Employee; Self; Dexcom, Inc. T.C. Walker: Employee; Self; Dexcom, Inc. D.A. Price: Employee; Self; Dexcom, Inc. Stock/Shareholder; Self; Johnson &amp; Johnson.

Genetic Diversity and Differentiation in Phoma betae Populations on Table Beet in New York and Washington States.

Phoma betae is an important seedborne pathogen of table beet worldwide that is capable of causing foliar, root, and damping-off diseases. Ten microsatellite and mating type markers were developed to investigate the genetics of P. betae populations in table beet root crops in New York and in table beet seed crops in Washington, from where table beet seed is predominantly sourced. The markers were used to characterize 175 isolates comprising five P. betae populations (two from New York and three from Washington), and they were highly polymorphic with an allelic range of 4 to 33 and an average of 11.7 alleles per locus. All populations had high genotypic diversity (Simpson's complement index = 0.857 to 0.924) and moderate allelic diversity (Nei's unbiased gene diversity = 0.582 to 0.653). Greater differentiation observed between populations from the two states compared with populations within the same state suggested that an external inoculum source, such as windblown ascospores, may be homogenizing the populations. However, most genetic diversity (87%) was among individual isolates within populations (pairwise index of population differentiation = 0.127; P = 0.001), suggesting that local within-field inoculum source(s), such as infested field debris or infected weeds, may also be important in initiating disease outbreaks. Standardized index of association, proportion of compatible pairs of loci, and mating type ratio calculations showed evidence for a mixed reproduction mode in all populations. These findings could be useful in designing more effective management strategies for diseases caused by P. betae in table beet production.

Children and their parents’ assessment of postoperative surgical pain: Agree or disagree?

ObjectiveThe purpose of this study is to compare postoperative pain scores between children undergoing tonsillectomy and adenoidectomy (T&A) surgery and their parents, identify potential predictors for this disagreement, and determine possible impact on analgesic administration. MethodsThis is a prospective longitudinal study conducted with children undergoing outpatient T&A in 4 major tertiary hospitals and their parents. Children and their parents were enrolled prior to surgery and completed baseline psychological instruments assessing parental anxiety (STAI), parental coping style (MBSS), child temperament (EAS) and parental medication administration attitude questionnaire (MAQ). Postoperatively, parents and children completed at-home pain severity ratings (Faces Pain Scale-Revised, children; Numeric Rating Scale, parents) on postoperative recovery days 1, 2, and 3, reflecting an overall pain level for the past 24 h. Parents also completed a log of analgesic administration. Based on postoperative pain scores, parent-child dyads were classified as overestimators (i.e., parents rated their child's pain higher than children rated their own pain), in agreement (i.e., rating in agreement), or underestimators (i.e., parents rated their child's pain lower than children rated their own pain). ResultsA significant proportion of parent-child pairs disagreed on pain ratings on postoperative days 1–3 (30.05%–35.95%). Of those pairs in disagreement, the majority of parents overestimated their child's pain on all three postoperative days, specifically such that a total of 24–26% parents overestimated their child's pain on postoperative days 1, 2, and 3. Repeated measures ANOVA demonstrated that parents in the overestimator group administered higher, though still within safe limits, amounts of ibuprofen and oxycodone (mg/day) than did the underestimator or agreement groups. Multiple regression models showed hospital site as the only independent predictor for postoperative pain rating disagreement between children and parents. ConclusionsSince parents overestimate their child's postoperative pain and may administer more analgesics to their child, it is essential to develop a standardized method of child pain assessment and a tailored recommended postoperative analgesic regimen amongst medical providers for children undergoing T&A.

Haiti Acute and Emergency Care Conference: descriptive analysis of an acute care continuing medical education program

# Background Several disasters over the past decade have highlighted the need for strong acute-care systems in Haiti. As part of a multifaceted approach to improving national acute-care training, the Research and Education consortium for Acute Care in Haiti (REACH) launched the inaugural Haiti Acute and Emergency Care Conference (HAECC). # Methods REACH is a Haitian-led, multinational collaboration based out of Saint Luc Hospital in Port-au-Prince. The HAECC was held in April, 2017. Pre- and post-course evaluation consisted of subjective and objective components. Differences between pre- and post-responses were determined using McNemar's test of paired proportions. # Results 57 participants from 21 hospitals in five Haitian departments were included. The majority (37/58, 63.8%) were physicians. Most (33/57, 57.9%) had no prior training in acute or emergency care, but 8/57 (14.0%) had taken ATLS/ACLS, 11/57 (19.3%) had taken a formal course not internationally recognized, and only 1/57 (1.8%) had completed acute care specialty training. 43.7% (25/57) reported routine access to point-of-care ultrasound. Following course completion, participants felt significantly more comfortable managing basic emergency conditions (up to 25/57, 43.9% increase, *P*\<0.01) and using ultrasound (up to 30/57, 52.6% increase, *P*\<0.01), but improvements on objective testing were not significant (ranging from -2 (-3.5%, *P*=1.00) to +5 (8.7%, *P*=0.15) change). # Conclusions While continued quality review is necessary for future iterations of the conference, the inaugural HAECC provided a useful first pass for current front-line providers in Haiti.

Effect of two alternative methods of pooling sputum prior to testing for tuberculosis with genexpert MTB/RIF

BackgroundPooling sputum specimens is one potential strategy for reducing the cost of using Xpert MTB/RIF, a rapid polymerase chain reaction (PCR)-based test, for the diagnosis of pulmonary tuberculosis. We sought to compare the sensitivity of two alternative method of pooling.MethodsPatients referred for assessment for TB, whose initial sputum was Xpert MTB positive, were recruited and their sputum specimens were pooled for analysis with sputum specimens that were Xpert MTB negative. Two alternative pooling strategies were employed: one in which the concentration of sample reagent (buffer) was maintained at 2:1 (standard), in accordance with the manufacturer’s instructions, and another in which the concentration of sample reagent was reduced to 1:1.ResultsWe tested 101 Xpert MTB positive sputum specimens. Among these, 96% of valid test results (95% confidence interval (CI) 89–99%) were positive using the “standard buffer method”. Using the “reduced buffer pooling” method 94% of valid test results (95% CI 87–98%) were positive. McNemar’s test for the difference in paired proportions did not reach statistical significance (P = 0.56).ConclusionWe have confirmed that pooling of two sputum specimens for testing in a single cartridge is a valid method of reducing the number of cartridges required when using Xpert MTB to detect pulmonary tuberculosis. Two alternative pooling strategies tested here yielded similar results.Trial registrationThe present study was conducted within the Active Casefinding in Tuberculosis (ACT3) Trial. The ACT3 Trial had been registered with Australian and New Zealand Clinical Trials Register on 8th April, 2014. The trial registration number is ACTRN12614000372684. (Retrospectively registered).

Stable isotopes of carbon reveal flexible pairing strategies in a migratory Arctic bird

Many birds change their partners every year and pairing may occur before arrival on the breeding grounds. Early pairing strategies can benefit mates by strengthening pair-bonds and increasing the rate of pre-breeding resource acquisition, leading to increased reproductive output and success, especially for migratory species breeding in seasonally-constrained environments like the Arctic. Despite the theorized and documented advantages of early pairing, we know rather little about pairing phenology in many species. Here, we test the use of a stable isotope (carbon δ13C) method to assign geographic origin of paired birds to examine pairing phenology in Arctic-breeding Common Eiders (Somateria mollissima borealis). During two consecutive years, we captured paired individuals upon their arrival at breeding grounds approximately 2–3 weeks before laying. Pairs with similar δ13C in their claws indicates that they paired during winter, while similar blood values (with no similarity in claws) would reveal pairs formed much later, during the pre-breeding period near or on the breeding grounds. While a large proportion of pairs (43%) appeared to pair on wintering grounds, an almost equal number (52%) likely paired within 1 month prior to arrival on the breeding grounds. The remaining 5% did not have an obvious pairing time. Despite this variability in pairing phenology, we found no significant differences in body condition between females or males which paired in winter or spring. In the year characterized with more challenging winter conditions, pairs formed in spring tended to have a higher breeding propensity than those formed in winter, although there were no detectable links to body condition. Delaying pairing until spring may be advantageous for Arctic-breeding eiders, although a specific mechanism is unknown. Future research focusing on the energetic costs and benefits for male eiders during these periods would help further understand pairing phenology and potential impacts on males of female breeding decisions.

A Systematic Review of Principal Component Analysis–Derived Dietary Patterns in Japanese Adults: Are Major Dietary Patterns Reproducible Within a Country?

Principal component analysis (PCA) has been widely used in nutritional epidemiology to derive dietary patterns. However, although PCA-derived dietary patterns are population-dependent, their reproducibility in different populations is largely unexplored. We aimed to investigate whether major dietary patterns are consistently identified among different populations within a country and, if so, how similar these dietary patterns are. We conducted a systematic review of PCA-derived dietary patterns in Japanese adults using PubMed and Web of Science for English articles and Ichushi-Web and CiNii databases for Japanese articles. We assessed the reproducibility of major dietary patterns using congruence coefficients (CCs), with values ≥0.80 considered to represent fair similarity. From 65 articles (80 studies) included in this review, 285 different dietary patterns were identified. Based on the names of these patterns, major dietary patterns were Western (n=34), Japanese (n=12), traditional (n=10), traditional Japanese (n=9), healthy (n=18), and prudent (n=9) patterns. When assessment was limited to high-quality data (i.e., studies based on a sample size ≥200 and use of a validated dietary assessment questionnaire or multiple-day dietary record), the median CC was low for Western (0.44), traditional (0.59), and traditional Japanese (0.31) patterns. Conversely, the median CC was 0.89 for healthy, 0.86 for prudent, and 0.80 for Japanese patterns; and the proportion of pairs with a CC ≥0.80 was 87.3%, 64.3%, and 50.0%, respectively. Characteristics shared among these 3 dietary patterns included higher intakes of mushrooms, seaweeds, vegetables, potatoes, fruits, pulses, and pickles. In conclusion, this systematic review showed that some of the major dietary patterns are relatively reproducible in different populations within a country, whereas others are not. This highlights the importance of careful interpretation of PCA-derived dietary patterns. Our findings in Japan should be confirmed in different countries and globally. This study was registered at https://www.crd.york.ac.uk/prospero/ as CRD42018087669.

Compatibility of pulse-pulse intervals with R-R intervals in assessing cardiac autonomic function and its relation to risks of atherosclerosis.

Objective:Heart rate variability (HRV) analysis using electrocardiographic R–R intervals (RRIs) in either a time or a frequency domain is a useful tool for assessing cardiac autonomic dysfunction in clinical research. For convenience, pulse–pulse intervals (PPIs) acquired by photoplethysmography have been used to assess HRV. However, the compatibility of PPI with RRI is controversial.Materials and Methods:In this study, we investigated the compatibility of PPI with RRI in five groups of participants, including nonoverweight young individuals with a body mass index (BMI) <24 kg/m2 (Group 1, n = 20, aged 18–40 years), overweight young individuals with a BMI ≥24 kg/m2 (Group 2, n = 13, aged 21–38 years), nonoverweight upper middle-aged individuals with a BMI <24 kg/m2 (Group 3, n = 21, aged 45–89 years), overweight upper middle-aged individuals with a BMI ≥24 kg/m2 (Group 4, n = 14, aged 43–74 years), and diabetic patients with a BMI ≥24 kg/m2 (Group 5, n = 19, aged 35–74 years). We then used cross-approximate entropy (CAE) to assess the compatibility between RRI and PPI and analyzed HRV in the time and frequency domains derived from PPR and RRI with traditional methods.Results:The CAE values in Group 1 were significantly lower than those in Group 2 (1.68 ± 0.16 vs. 1.78 ± 0.15, P = 0.041), Group 3 (1.68 ± 0.16 vs. 2.05 ± 0.27, P < 0.001), Group 4 (1.68 ± 0.16 vs. 1.87 ± 0.23, P = 0.023), and Group 5 (1.68 ± 0.16 vs. 2.09 ± 0.23, P < 0.001). There were no significant differences in HRV acquired by PPI and RRI, except for proportion of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording in Group 1. All HRVs derived from PPI were different from those acquired from RRI in the other groups.Conclusion:PPI may be an alternative parameter for effectively assessing cardiac autonomic function in nonoverweight healthy individuals. It should be used carefully in overweight, elderly, or diabetic individuals.

134: The immunological basis for villitis of unknown etiology: concordance within dizygotic vs. monozygotic twins

Villitis of unknown origin (VUE) is a chronic inflammatory placental pathology that is associated with fetal growth restriction and stillbirth. It has been suggested that VUE represents a form of host-versus-graft disease, in which maternal T-cells react to ‘foreign’ fetal antigens. However, data in support of this mechanism is scarce. Our objective was to compare the proportion of twin pairs concordant for VUE (i.e., proportion of twin pairs in which placentas of both fetuses are affected by VUE) between monozygotic (MZ) and DZ twins. We hypothesized that if the suggested immunological mechanism is true, the proportion of concordant pairs would be higher among MZ twins (who share the same genetic material) than among DZ twins. We performed a retrospective cohort study of all women with twin gestations at a single, tertiary centre (2001-2015), who had placental pathology data. Monochorionic placentas were examined as separate placentas according to the relative placental territory attributed to each twin. The proportion of twin pairs concordant for VUE was compared between monochorionic twins (representing MZ twins) and opposite-sex dichorionic twins (representing DZ twins). Overall, 561 DZ twins and 347 MZ twins were included in the analysis. The MZ group was characterized by lower gestational age at delivery and lower birth weight (Table). The overall rate of VUE in the DZ and MZ twin pregnancies was 8.7% (n=49) and 7.5% (n=26), respectively (p=0.51). There were no difference between DZ and MZ twins with regard to the proportion of twin pairs concordant for VUE (3.0% vs. 2.6%, respectively, p=0.70) (Table). When using only twin pregnancies affected by VUE as the denominator, the proportion of concordant pairs for VUE in DZ and MZ twins was similar as well at 34.7% (17/49) and 34.6% (9/26) (p=0.99). The proportion of twin pairs concordant for VUE is MZ twins is similar to that in DZ twins. These finding questions the current hypothesis regarding the mechanisms underlying VUE.

The SmartTarget Biopsy Trial: A Prospective, Within-person Randomised, Blinded Trial Comparing the Accuracy of Visual-registration and Magnetic Resonance Imaging/Ultrasound Image-fusion Targeted Biopsies for Prostate Cancer Risk Stratification

BackgroundMultiparametric magnetic resonance imaging (mpMRI)-targeted prostate biopsies can improve detection of clinically significant prostate cancer and decrease the overdetection of insignificant cancers. It is unknown whether visual-registration targeting is sufficient or augmentation with image-fusion software is needed. ObjectiveTo assess concordance between the two methods. Design, setting, and participantsWe conducted a blinded, within-person randomised, paired validating clinical trial. From 2014 to 2016, 141 men who had undergone a prior (positive or negative) transrectal ultrasound biopsy and had a discrete lesion on mpMRI (score 3–5) requiring targeted transperineal biopsy were enrolled at a UK academic hospital; 129 underwent both biopsy strategies and completed the study. InterventionThe order of performing biopsies using visual registration and a computer-assisted MRI/ultrasound image-fusion system (SmartTarget) on each patient was randomised. The equipment was reset between biopsy strategies to mitigate incorporation bias. Outcome measurements and statistical analysisThe proportion of clinically significant prostate cancer (primary outcome: Gleason pattern ≥3+4=7, maximum cancer core length ≥4mm; secondary outcome: Gleason pattern ≥4+3=7, maximum cancer core length ≥6mm) detected by each method was compared using McNemar's test of paired proportions. Results and limitationsThe two strategies combined detected 93 clinically significant prostate cancers (72% of the cohort). Each strategy detected 80/93 (86%) of these cancers; each strategy identified 13 cases missed by the other. Three patients experienced adverse events related to biopsy (urinary retention, urinary tract infection, nausea, and vomiting). No difference in urinary symptoms, erectile function, or quality of life between baseline and follow-up (median 10.5 wk) was observed. The key limitations were lack of parallel-group randomisation and a limit on the number of targeted cores. ConclusionsVisual-registration and image-fusion targeting strategies combined had the highest detection rate for clinically significant cancers. Targeted prostate biopsy should be performed using both strategies together. Patient summaryWe compared two prostate cancer biopsy strategies: visual registration and image fusion. A combination of the two strategies found the most clinically important cancers and should be used together whenever targeted biopsy is being performed.

Power in pairs: assessing the statistical value of paired samples in tests for differential expression

BackgroundWhen genomics researchers design a high-throughput study to test for differential expression, some biological systems and research questions provide opportunities to use paired samples from subjects, and researchers can plan for a certain proportion of subjects to have paired samples. We consider the effect of this paired samples proportion on the statistical power of the study, using characteristics of both count (RNA-Seq) and continuous (microarray) expression data from a colorectal cancer study.ResultsWe demonstrate that a higher proportion of subjects with paired samples yields higher statistical power, for various total numbers of samples, and for various strengths of subject-level confounding factors. In the design scenarios considered, the statistical power in a fully-paired design is substantially (and in many cases several times) greater than in an unpaired design.ConclusionsFor the many biological systems and research questions where paired samples are feasible and relevant, substantial statistical power gains can be achieved at the study design stage when genomics researchers plan on using paired samples from the largest possible proportion of subjects. Any cost savings in a study design with unpaired samples are likely accompanied by underpowered and possibly biased results.