Reliability of the Danish Aerospace Corporation Portable Pulmonary Function System

Metabolic gas analysis is a critical component of investigations that measure cardio-pulmonary exercise responses during and after long-duration spaceflight. The primary purpose of the current study was to determine the reliability and intra-subject repeatability of a metabolic gas analysis device, the Portable Pulmonary Function System (PPFS), designed for use on the International Space Station (ISS). The second objective of this study was to directly compare PPFS measurements of expired oxygen and carbon dioxide (FEO2 and FECO2) to values obtained from a well-validated clinical metabolic gas analysis system (ParvoMedics TrueOne (c) [PM]). Eight subjects performed four peak cycle tests to maximal exertion. The first test was used to prescribe work rates for the subsequent test sessions. Metabolic gas analysis for this test was performed by the PM, but samples of FEO2 and FECO2 also were simultaneously collected for analysis by the PPFS. Subjects then performed three additional peak cycle tests, consisting of three 5-min stages designed to elicit 25%, 50%, and 75% maximal oxygen consumption (VO2max) followed by stepwise increases of 25 W/min until subjects reached volitional exhaustion. Metabolic gas analysis was performed using the PPFS for these tests. Intraclass correlation coefficients (ICC), within-subject standard deviations (WS SD), and coefficients of variation (CV%) were calculated for the repeated exercise tests. Mixed model regression analysis was used to compare paired FEO2 and FECO2 values obtained from the PPFS and the PM during the initial test. The ICC values for oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilation (VE) indicate that the PPFS is highly reliable (0.79 to 0.99) for all exercise levels tested; however, ICCs for respiratory exchange ratio (RER) were low ( 0.11 - 0.51), indicating poor agreement between trials during submaximal and maximal exercise. Overall, CVs ranged from 1.6% to 6.7% for all measurements, a finding consistent with reported values that were obtained using other metabolic gas analysis techniques. The PPFS and PM produced comparable FEO2 data; however, there was less agreement between measures of FECO2 obtained from the two devices, particularly at lower CO2 concentrations. The PPFS appears, in practically all respects, to yield highly reliable metabolic gas analysis data. Lower reliability of RER measurements reported in the literature and likely is not a function of the PPFS device. Further examination of PPFS CO2 data is warranted to better understand the limitations of these PPFS measurements. Overall, the PPFS when used for repeated measures of cardio-pulmonary exercise should provide accurate and reliable data for studies of human adaptation to spaceflight

Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified

Peak Oxygen Uptake during and after Long-duration Space Flight

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion

Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting

Background: Well-validated models of maternal behavior in small-brain mammals posit a central role of oxytocin in parenting, by reducing stress and enhancing the reward value of social interactions with offspring. In contrast, human studies are only beginning to gain insights into how oxytocin modulates maternal behavior and affiliation. Methods: To explore associations between oxytocin receptor genes and maternal parenting behavior in humans, we conducted a genetic imaging study of women selected to exhibit a wide range of observed parenting when their children were 4-6 years old. Results: In response to child stimuli during functional magnetic resonance imaging (fMRI), hemodynamic responses in brain regions that mediate affect, reward, and social behavior were significantly correlated with observed positive parenting. Furthermore, single nucleotide polymorphisms (SNPs) (rs53576 and rs1042778) in the gene encoding the oxytocin receptor were significantly associated with both positive parenting and hemodynamic responses to child stimuli in orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus. Conclusions: These findings contribute to the emerging literature on the role of oxytocin in human social behavior and support the feasibility of tracing biological pathways from genes to neural regions to positive maternal parenting behaviors in humans using genetic imaging methods. © 2014 Michalska, Decety, Liu, Chen, Martz, Jacob, Hipwell, Lee, Chronis-Tuscano, Waldman and Lahey

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Validity of estimated cardiorespiratory fitness in patients with primary breast cancer

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.Background: Estimated peak oxygen consumption (Vo2peak) is widely used in oncology; however, estimated Vo2peak equations were developed in noncancer settings. Objectives: The aim of this study was to evaluate the validity of estimated Vo2peak in women with primary breast cancer and to develop oncology-specific estimated Vo2peak equations. Methods: Vo2peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo2peak. New equations were developed using patient and peak (Oncpeak) or submaximal (Oncsub) exercise test characteristics. Results: The median differences between measured and estimated Vo2peak were 7.0 mL O2·kg−1·min−1, 3.9 mL O2·kg−1·min−1, and −0.2 mL O2·kg−1·min−1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo2peak values within ±3.5 mL O2·kg−1·min−1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Oncpeak and OncSub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo2peak were 0.02 mL O2·kg−1·min−1 (Oncpeak) and −0.2 mL O2·kg−1·min−1 (Oncsub). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo2peak values were within ±3.5 mL O2·kg−1·min−1 of the measured Vo2peak values for Oncpeak and Oncsub, respectively. Conclusions: HF-FRIEND or oncology-specific equations could be applied to estimate Vo2peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer [EXCITE]; NCT01186367publishedVersionInstitutt for fysisk prestasjonsevne / Department of Physical Performanc

Pathologist Concordance for Ovarian Carcinoma Subtype Classification and Identification of Relevant Histologic Features Using Microscope and Whole Slide Imaging.

CONTEXT.—: Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined. OBJECTIVE.—: To assess pathologist performance for the histologic subtyping of individual sections of ovarian carcinomas using a light microscope and WSI. DESIGN.—: A panel of 3 experienced gynecologic pathologists provided reference subtype diagnoses for 212 histologic sections from 109 ovarian carcinomas based on optical microscopy review. Two additional attending pathologists provided diagnoses and also identified the presence of a set of 8 histologic features important for ovarian tumor subtyping. Two experienced gynecologic pathologists and 2 fellows reviewed the corresponding WSI images for subtype classification and feature identification. RESULTS.—: Across pathologists specialized in gynecologic pathology, concordance with the reference diagnosis for the 5 major ovarian carcinoma subtypes was significantly higher for a pathologist reading on a microscope than each of 2 pathologists reading on WSI. Differences were primarily due to more frequent classification of mucinous carcinomas as endometrioid with WSI. Pathologists had generally low agreement in identifying histologic features important to ovarian tumor subtype classification with either an optical microscopy or WSI. This result suggests the need for refined histologic criteria for identifying such features. Interobserver agreement was particularly low for identifying intracytoplasmic mucin with WSI. Inconsistencies in evaluating nuclear atypia and mitoses with WSI were also observed. CONCLUSIONS.—: Further research is needed to specify the reasons for these diagnostic challenges and to inform users and manufacturers of WSI technology

Effects of Gender Bias and Stereotypes in Surgical Training

Importance: Factors contributing to underrepresentation of women in surgery are incompletely understood. Pro-male bias and stereotype threat appear to contribute to gender imbalance in surgery. Objectives: To evaluate the association between pro-male gender bias and career engagement and the effect of stereotype threat on skill performance among trainees in academic surgery. Design, Setting, and Participants: A 2-phase study with a double-blind, randomized clinical trial component was conducted in 3 academic general surgery training programs. Residents were recruited between August 1 and August 15, 2018, and the study was completed at the end of that academic year. In phase 1, surveys administered 5 to 6 months apart investigated the association of gender bias with career engagement. In phase 2, residents were randomized 1:1 using permuted-block design stratified by site, training level, and gender to receive either a trigger of or protection against stereotype threat. Immediately after the interventions, residents completed the Fundamentals of Laparoscopic Surgery (FLS) assessment followed by a final survey. A total of 131 general surgery residents were recruited; of these 96 individuals with academic career interests met eligibility criteria; 86 residents completed phase 1. Eighty-five residents were randomized in phase 2, and 4 residents in each arm were lost to follow-up. Intervention: Residents read abstracts that either reported that women had worse laparoscopic skill performance than men (trigger of stereotype threat [A]) or had no difference in performance (protection against stereotype threat [B]). Main Outcomes and Measures: Association between perception of pro-male gender bias and career engagement survey scores (phase 1) and stereotype threat intervention and FLS scores (phase 2) were the outcomes. Intention-to-treat analysis was conducted. Results: Seventy-seven residents (38 women [49.4%]) completed both phases of the study. The association between pro-male gender bias and career engagement differed by gender (interaction coefficient, -1.19; 95% CI, -1.90 to -0.49; P = .02); higher perception of bias was associated with higher engagement among men (coefficient, 1.02; 95% CI, 0.19-2.24; P = .04), but no significant association was observed among women (coefficient, -0.25; 95% CI, -1.59 to 1.08; P = .50). There was no evidence of a difference in FLS score between interventions (mean [SD], A: 395 [150] vs B: 367 [157]; P = .51). The response to stereotype threat activation was similar in men and women (interaction coefficient, 15.1; 95% CI, -124.5 to 154.7; P = .39). The association between stereotype threat activation and FLS score differed by gender across levels of susceptibility to stereotype threat (interaction coefficient, -35.3; 95% CI, -47.0 to -23.6; P = .006). Higher susceptibility to stereotype threat was associated with lower FLS scores among women who received a stereotype threat trigger (coefficient, -43.4; 95% CI, -48.0 to -38.9; P = .001). Conclusions and Relevance: Perception of pro-male bias and gender stereotypes may influence career engagement and skill performance, respectively, among surgical trainees. Trial Registration: ClinicalTrials.gov Identifier: NCT03623009