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The population of Newfoundland and Labrador (NL) is largely derived from settlers who migrated primarily from England and Ireland in the 1700s-1800s. Previously described as an isolated founder population, based on historical and demographic studies, data on the genetic ancestry of this population remains fragmentary. Here we describe the largest investigation of patrilineal ancestry in NL. To determine the paternal genetic structure of the population, 1,110 Y chromosomes from an NL-based cohort were analyzed using 5,761 Y-specific SNPs. We identified 160 distinct terminal haplogroups, the majority of which (71.4%) belong to the R1b haplogroup. When compared with global reference populations, the NL population haplogroup composition and frequencies primarily resemble those observed in English and Irish ancestral source populations. There is also evidence of genetic contributions from Basque, French, Portuguese, and Spanish fishermen and early settlers who frequented NL. Interestingly, the observed population structure shows geographical and religious clustering that can be associated with the settlement of the ancestral source populations from predominantly Protestant, England, and Catholic, Ireland respectively. For example, the R1b-M222 haplogroup, seen in people of Irish descent, is found clustered in the Irish-settled Southeast region of NL. The clustering and expansion of Y haplogroups in conjunction with the geographical and religious clusters illustrate that limited subsequent in-migration, geographic isolation, and societal factors have contributed to the genetic substructure of the NL population and its designation as a founder population.
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BACKGROUND: Perinatal depression (including antenatal-, postnatal-, and depression that spans both timepoints) is a prevalent disorder with high morbidity that affects both mother and child. Even though the full biological blueprints of perinatal depression remain incomplete, multiple studies indicate that, at least for antenatal depression, the disorder has an inflammatory component likely linked to a dysregulation of the enzymatic kynurenine pathway. The production of neuroactive metabolites in this pathway, including quinolinic acid (QUIN), is upregulated in the placenta due to the multiple immunological roles of the metabolites during pregnancy. Since neuroactive metabolites produced by the pathway also may affect mood by directly affecting glutamate neurotransmission, we sought to investigate whether the placental expression of kynurenine pathway enzymes controlling QUIN production was associated with both peripheral inflammation and depressive symptoms during pregnancy. METHODS: 68 placentas obtained at birth were analyzed using qPCR to determine the expression of kynurenine pathway enzymes. Cytokines and metabolites were quantified in plasma using high-sensitivity electroluminescence and ultra-performance liquid chromatography, respectively. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) throughout pregnancy and the post-partum. Associations between these factors were assessed using robust linear regression with ranked enzymes. RESULTS: Low placental quinolinate phosphoribosyl transferase (QPRT), the enzyme responsible for degrading QUIN, was associated with higher IL-6 and higher QUIN/kynurenic acid ratios at the 3rd trimester. Moreover, women with severe depressive symptoms in the 3rd trimester had significantly lower placental expression of both QPRT and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD); impaired activity of these two enzymes leads to QUIN accumulation. CONCLUSION: Overall, our data support that a compromised placental environment, featuring low expression of critical kynurenine pathway enzymes is associated with increased levels of plasma cytokines and the dysregulated kynurenine metabolite pattern observed in depressed women during pregnancy.
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Depresión , Inflamación , Quinurenina , Placenta , Ácido Quinolínico , Humanos , Femenino , Embarazo , Quinurenina/metabolismo , Quinurenina/sangre , Placenta/metabolismo , Adulto , Inflamación/metabolismo , Depresión/metabolismo , Ácido Quinolínico/metabolismo , Ácido Quinolínico/sangre , Citocinas/metabolismo , Complicaciones del Embarazo/metabolismo , Carboxiliasas/metabolismo , PentosiltransferasaRESUMEN
Parametric splines are popular tools for precision optical metrology of complex freeform surfaces. However, as a promising topologically unconstrained solution, existing T-spline fitting techniques, such as improved global fitting, local fitting, and split-connect algorithms, still suffer the problems of low computational efficiency, especially in the case of large data scales and high accuracy requirements. This paper proposes a speed-improved algorithm for fast, large-scale freeform point cloud fitting by stitching locally fitted T-splines through three steps of localized operations. Experiments show that the proposed algorithm produces a three-to-eightfold efficiency improvement from the global and local fitting algorithms, and a two-to-fourfold improvement from the latest split-connect algorithm, in high-accuracy and large-scale fitting scenarios. A classical Lena image study showed that the algorithm is at least twice as fast as the split-connect algorithm using fewer than 80% control points of the latter.
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The founder population of Newfoundland and Labrador (NL) is a unique genetic resource, in part due to its geographic and cultural isolation, where historical records describe a migration of European settlers, primarily from Ireland and England, to NL in the 18th and 19th centuries. Whilst its historical isolation, and increased prevalence of certain monogenic disorders are well appreciated, details of the fine-scale genetic structure and ancestry of the population are lacking. Understanding the genetic origins and background of functional, disease causing, genetic variants would aid genetic mapping efforts in the Province. Here, we leverage dense genome-wide SNP data on 1,807 NL individuals to reveal fine-scale genetic structure in NL that is clustered around coastal communities and correlated with Christian denomination. We show that the majority of NL European ancestry can be traced back to the south-east and south-west of Ireland and England, respectively. We date a substantial population size bottleneck approximately 10-15 generations ago in NL, associated with increased haplotype sharing and autozygosity. Our results reveal insights into the population history of NL and demonstrate evidence of a population conducive to further genetic studies and biomarker discovery.
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Genética de Población , Población Blanca , Humanos , Terranova y Labrador , Irlanda , Migración HumanaRESUMEN
Camera-based methods for optical coordinate metrology, such as digital fringe projection, rely on accurate calibration of the cameras in the system. Camera calibration is the process of determining the intrinsic and distortion parameters which define the camera model and relies on the localisation of targets (in this case, circular dots) within a set of calibration images. Localising these features with sub-pixel accuracy is key to providing high quality calibration results which in turn allows for high quality measurement results. A popular solution to the localisation of calibration features is provided in the OpenCV library. In this paper, we adopt a hybrid machine learning approach where an initial localisation is given by OpenCV which is then refined through a convolutional neural network based on the EfficientNet architecture. Our proposed localisation method is then compared with the OpenCV locations without refinement, and to an alternative refinement method based on traditional image processing. We show that under ideal imaging conditions, both refinement methods provide a reduction in the mean residual reprojection error of approximately 50%. However, in adverse imaging conditions, with high noise levels and specular reflection, we show that the traditional refinement degrades the results given by pure OpenCV, increasing the mean residual magnitude by 34%, which corresponds to 0.2 pixels. In contrast, the EfficientNet refinement is shown to be robust to the unideal conditions and is still able to reduce the mean residual magnitude by 50% compared to OpenCV. The EfficientNet feature localisation refinement, therefore, enables a greater range of viable imaging positions across the measurement volume. leading to more robust camera parameter estimations.
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BACKGROUND: Acute kidney injury (AKI) is common in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to explore the changes in AKI epidemiology between the first and the second COVID wave in the United Kingdom (UK). METHODS: This was an observational study of critically ill adult patients with COVID-19 in an expanded tertiary care intensive care unit (ICU) in London, UK. Baseline characteristics, organ support, COVID-19 treatments, and patient and kidney outcomes up to 90 days after discharge from hospital were compared. RESULTS: A total of 772 patients were included in the final analysis (68% male, mean age 56 ± 13.6). Compared with wave 1, patients in wave 2 were older, had higher body mass index and clinical frailty score, but lower baseline serum creatinine and C-reactive protein (CRP). The proportion of patients receiving invasive mechanical ventilation (MV) on ICU admission was lower in wave 2 (61% vs 80%; p < 0.001). AKI incidence within 14 days of ICU admission was 76% in wave 1 and 51% in wave 2 (p < 0.001); in wave 1, 32% received KRT compared with 13% in wave 2 (p < 0.001). Patients in wave 2 had significantly lower daily cumulative fluid balance (FB) than in wave 1. Fewer patients were dialysis dependent at 90 days in wave 2 (1% vs. 4%; p < 0.001). CONCLUSIONS: In critically ill adult patients admitted to ICU with COVID-19, the risk of AKI and receipt of KRT significantly declined in the second wave. The trend was associated with less MV, lower PEEP and lower cumulative FB. TRIAL REGISTRATION: NCT04445259.
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BACKGROUND: Acute kidney injury (AKI) is a frequent complication in patients with severe respiratory failure receiving extracorporeal membrane oxygenation (ECMO). However, little is known of long-term kidney function in ECMO survivors. We aimed to assess the long-term mortality and kidney outcomes in adult patients treated with veno-venous ECMO (VV-ECMO). METHODS: This was a single-centre retrospective study of adult patients (≥ 18 years old) who were treated with VV-ECMO at a commissioned ECMO centre in the UK between 1st September 2010, and 30th November 2016. AKI was defined and staged using the serum creatinine and urine output criteria of the Kidney Diseases: Improving Global Outcomes (KDIGO) classification. The primary outcome was 1-year mortality. Secondary outcomes were long-term mortality (up to March 2020), 1-year incidence of end-stage kidney disease (ESKD) or chronic kidney disease (CKD) among AKI patients who received renal replacement therapy (AKI-RRT), AKI patients who did not receive RRT (AKI-no RRT) and patients without AKI (non-AKI). RESULTS: A total of 300 patients [57% male; median age 44.5; interquartile range (IQR) 34-54] were included in the final analysis. Past medical histories included diabetes (12%), hypertension (17%), and CKD (2.3%). The main cause of severe respiratory failure was pulmonary infection (72%). AKI occurred in 230 patients (76.7%) and 59.3% received renal replacement therapy (RRT). One-year mortality was 32% in AKI-RRT patients vs. 21.4% in non-AKI patients (p = 0.014). The median follow-up time was 4.35 years. Patients who received RRT had a higher risk of 1-year mortality than those who did not receive RRT (adjusted HR 1.80, 95% CI 1.06, 3.06; p = 0.029). ESKD occurred in 3 patients, all of whom were in the AKI-RRT group. At 1-year, 41.2% of survivors had serum creatinine results available. Among these, CKD was prevalent in 33.3% of AKI-RRT patients vs. 4.3% in non-AKI patients (p = 0.004). CONCLUSIONS: VV-EMCO patients with AKI-RRT had high long-term mortality. Monitoring of kidney function after hospital discharge was poor. In patients with follow-up creatinine results available, the CKD prevalence was high at 1 year, especially in AKI-RRT patients. More awareness about this serious long-term complication and appropriate follow-up interventions are required.
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The simultaneous measurement of all six degrees of freedom of motion error for a linear stage is significantly faster than methods that measure each degree of freedom separately. However, in current simultaneous measurement methods, error crosstalk issues significantly affect measurement accuracy. In this paper, a direct and simple crosstalk decoupling simultaneous measurement method to determine the six degrees of freedom of motion error of a linear stage is proposed. Based on the combination of single-frequency laser interferometry and laser self-collimation, a novel, to the best of our knowledge, optical configuration with a complete error decoupling relationship is designed, and a mathematical model is derived for error decoupling to address the crosstalk issue. A prototype system based on the new method is developed, and experiments are conducted to verify its effectiveness. Analysis shows that, compared with a commercial laser interferometer for linear stage measurement, the deviations of the positioning, horizontal straightness, vertical straightness, roll, pitch, and yaw errors are±0.50µm, ±0.58µm, ±0.50µm, ±1.02in., ±0.72in., and ±0.87in. respectively, over a 200 mm measurement range.
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Depression during and after pregnancy affects up to 20% of pregnant women, but the biological underpinnings remain incompletely understood. As pregnancy progresses, the immune system changes to facilitate fetal development, leading to distinct fluctuations in the production of pro-inflammatory factors and neuroactive tryptophan metabolites throughout the peripartum period. Therefore, it is possible that depression in pregnancy could constitute a specific type of inflammation-induced depression. Both inflammatory factors and kynurenine metabolites impact neuroinflammation and glutamatergic neurotransmission and can therefore affect mood and behavior. To determine whether cytokines and kynurenine metabolites can predict the development of depression in pregnancy, we analyzed blood samples and clinical symptoms in 114 women during each trimester and the postpartum. We analyzed plasma IL-1ß, IL-2, -6, -8, -10, TNF, kynurenine, tryptophan, serotonin, kynurenic- quinolinic- and picolinic acids and used mixed-effects models to assess the association between biomarkers and depression severity. IL-1ß and IL-6 levels associated positively with severity of depressive symptoms across pregnancy and the postpartum, and that the odds of experiencing significant depressive symptoms increased by >30% per median absolute deviation for both IL-1ß and IL-6 (both P = 0.01). A combination of cytokines and kynurenine metabolites in the 2nd trimester had a >99% probability of accurately predicting 3rd trimester depression, with an ROC AUC > 0.8. Altogether, our work shows that cytokines and tryptophan metabolites can predict depression during pregnancy and could be useful as clinical markers of risk. Moreover, inflammation and kynurenine pathway enzymes should be considered possible therapeutic targets in peripartum depression.
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Depresión , Triptófano , Citocinas , Femenino , Humanos , Quinurenina , Enfermedades Neuroinflamatorias , EmbarazoRESUMEN
The capability of optical surface topography measurement methods for measurement of steep and tilted surfaces is investigated through modelling of a coherence scanning interferometer. Of particular interest is the effect on the interference signal and measured topography when tilting the object at angles larger than the numerical aperture slope limit (i.e. the specular reflection limit) of the instrument. Here we use theoretical modelling to predict the results across a range of tilt angles for a blazed diffraction grating. The theoretically predicted interference patterns and surface height measurements are then verified directly with experimental measurements. Results illustrate the capabilities, limitations and modelling methods for interferometers to measure beyond the specular reflection limit.
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Leading organisations recommend follow-up of acute kidney injury (AKI) survivors, as these patients are at risk of long-term complications and increased mortality. Information transfer between specialties and from tertiary to primary care is essential to ensure timely and appropriate follow-up. Our aim was to examine the association between completeness of discharge documentation and subsequent follow-up of AKI survivors who received kidney replacement therapy (KRT) in the Intensive Care Unit (ICU). We retrospectively analysed the data of 433 patients who had KRT for AKI during ICU admission in a tertiary care centre in the UK between June 2017 and May 2018 and identified patients who were discharged from hospital alive. Patients with pre-existing end-stage kidney disease and patients who were transferred from hospitals outside the catchment area were excluded. The primary objective was to assess the completeness of discharge documentation from critical care and hospital; secondary objectives were to determine cardiovascular medications reconciliation after AKI, and to investigate kidney care and outcomes at 1 year. The development of AKI and the need for KRT were mentioned in 85 and 82% of critical care discharge letters, respectively. Monitoring of kidney function post-discharge was recommended in 51.6% of critical care and 36.3% of hospital discharge summaries. Among 35 patients who were prescribed renin-angiotensin-aldosterone system inhibitors before hospitalisation, 15 (42.9%) were not re-started before discharge from hospital. At 3 months, creatinine and urine protein were measured in 88.2 and 11.8% of survivors, respectively. The prevalence of chronic kidney disease stage III or worse increased from 27.2% pre-hospitalisation to 54.9% at 1 year (p < 0.001). Our data demonstrate that discharge summaries of patients with AKI who received KRT lacked essential information. Furthermore, even in patients with appropriate documentation, renal follow-up was poor suggesting the need for more education and streamlined care pathways.
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BACKGROUND: There are limited data on acute kidney injury (AKI) progression and long-term outcomes in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to describe the prevalence and risk factors for development of AKI, its subsequent clinical course and AKI progression, as well as renal recovery or dialysis dependence and survival in this group of patients. METHODS: This was a retrospective observational study in an expanded tertiary care intensive care unit in London, United Kingdom. Critically ill patients admitted to ICU between 1st March 2020 and 31st July 2020 with confirmed SARS-COV2 infection were included. Analysis of baseline characteristics, organ support, COVID-19 associated therapies and their association with mortality and outcomes at 90 days was performed. RESULTS: Of 313 patients (70% male, mean age 54.5 ± 13.9 years), 240 (76.7%) developed AKI within 14 days after ICU admission: 63 (20.1%) stage 1, 41 (13.1%) stage 2, 136 (43.5%) stage 3. 113 (36.1%) patients presented with AKI on ICU admission. Progression to AKI stage 2/3 occurred in 36%. Risk factors for AKI progression were mechanical ventilation [HR (hazard ratio) 4.11; 95% confidence interval (CI) 1.61-10.49] and positive fluid balance [HR 1.21 (95% CI 1.11-1.31)], while steroid therapy was associated with a reduction in AKI progression (HR 0.73 [95% CI 0.55-0.97]). Kidney replacement therapy (KRT) was initiated in 31.9%. AKI patients had a higher 90-day mortality than non-AKI patients (34% vs. 14%; p < 0.001). Dialysis dependence was 5% at hospital discharge and 4% at 90 days. Renal recovery was identified in 81.6% of survivors at discharge and in 90.9% at 90 days. At 3 months, 16% of all AKI survivors had chronic kidney disease (CKD); among those without renal recovery, the CKD incidence was 44%. CONCLUSIONS: During the first COVID-19 wave, AKI was highly prevalent among severely ill COVID-19 patients with a third progressing to severe AKI requiring KRT. The risk of developing CKD was high. This study identifies factors modifying AKI progression, including a potentially protective effect of steroid therapy. Recognition of risk factors and monitoring of renal function post-discharge might help guide future practice and follow-up management strategies. Trial registration NCT04445259.
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We introduce an iteration-free approach, based on a centroid algorithm with a locally adaptive threshold, for nanometer-level peak position localization of the axial response signal in confocal microscopy. This approach has localization accuracies that are near theoretical limits, especially when there is a small number of sampling points within the discrete signal. The algorithm is also orders of magnitude faster compared to fitting schemes based on maximum likelihood estimation. Simulations and experiments demonstrate the localization performance of the approach.
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PURPOSE: To evaluate whether total FSH dose was negatively correlated with number of oocytes retrieved in a large data set where previously, a negative correlation between FSH dose and live birth rate was identified. METHODS: Data from 650,637 fresh autologous in vitro fertilization (IVF) cycles reported to the Society for Assisted Reproductive Technology between 2004 and 2012 were included. Logistic regression analysis was performed to determine if the relationship between total FSH dose used during ART with number of oocytes retrieved was impacted by the patient's health prognosis, age, BMI, ovarian stimulation protocol, or infertility diagnosis. RESULTS: The number of oocytes retrieved was negatively correlated with FSH dose (P < 0.0001). Regardless of patient prognosis, age, BMI, ovarian stimulation protocol, and infertility diagnosis, the highest number of oocytes retrieved was in the 1001-2000 IU FSH group, and was 36-51% lower in the > 5000 IU compared with the optimal, 1001-2000 IU, FSH groups. Overall, ~80% of patients received FSH doses outside of the optimal FSH dose. Moreover, 61% of good prognosis patients (excludes individuals likely prescribed higher FSH doses) received doses exceeding the optimal dose range. CONCLUSION: The inverse relationship between FSH dose and the number of oocytes retrieved independent of patient age or health implies that excessive FSH doses during ART may be detrimental to oocyte retrieval.
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Tasa de Natalidad , Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Recuperación del Oocito/métodos , Adulto , Índice de Masa Corporal , Relación Dosis-Respuesta a Droga , Endometriosis/fisiopatología , Femenino , Fertilización In Vitro/estadística & datos numéricos , Humanos , Infertilidad Femenina/terapia , Persona de Mediana Edad , Recuperación del Oocito/estadística & datos numéricos , Síndrome del Ovario Poliquístico/fisiopatología , Embarazo , Técnicas Reproductivas AsistidasRESUMEN
Surface topography measuring interference microscopy is a three-dimensional (3D) imaging technique that provides quantitative analysis of industrial and biomedical specimens. Many different instrument modalities and configurations exist, but they all share the same theoretical foundation. In this paper, we discuss a unified theoretical framework for 3D image (interferogram) formation in interference microscopy. We show how the scattered amplitude is linearly related to the surface topography according to the Born and the Kirchhoff approximations and highlight the main differences and similarities of each. With reference to the Ewald and McCutchen spheres, the relationship between the spatial frequencies that characterize the illuminating and scattered waves, and those that characterize the object, are defined and formulated as a 3D linear filtering process. It is shown that for the case of near planar surfaces, the 3D filtering process can be reduced to two dimensions under the small height approximation. However, the unified 3D framework provides significant additional insight into the scanning methods used in interference microscopy, effects such as interferometric defocus and ways to mitigate errors introduced by aberrations of the optical system. Furthermore, it is possible to include the nonlinear effects of multiple scattering into the generalized framework. Finally, we consider the inherent nonlinearities introduced when estimating surface topography from the recorded interferogram.
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In chromatic confocal microscopy, the signal characteristics influence the accuracy of the signal processing, which in turn determines measurement performance. Thus, a full understanding of the spectral characteristics is critical to enhance the measurement performance. Existing spectral models only describe the signal intensity-wavelength characteristics, without taking the displacement-wavelength relation into consideration. These models require prior knowledge of the optical design, which reduces the effectiveness in the optical design process. In this paper, we develop a two-dimensional spectral signal model to describe the signal intensity-wavelength-displacement characteristics in chromatic confocal microscopy without prior knowledge of the optical design layout. With this model, the influence of the dimensional characteristics of the confocal setup and the displacement-wavelength characteristics and monochromatic aberrations of the hyperchromatic objective are investigated. Experimental results are presented to illustrate the effectiveness of our signal model. Using our model, further evaluation of the spectral signal can be used to enhance the measurement performance of chromatic confocal microscopy.
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The design of innovative reference aspheric and freeform optical elements was investigated with the aim of calibration and verification of ultra-high accurate measurement systems. The verification is dedicated to form error analysis of aspherical and freeform optical surfaces based on minimum zone fitting. Two thermo-invariant material measures were designed, manufactured using a magnetorheological finishing process and selected for the evaluation of a number of ultra-high-precision measurement machines. All collected data sets were analysed using the implemented robust reference minimum zone (Hybrid Trust Region) fitting algorithm to extract the values of form error. Agreement among the results of several partners was observed, which demonstrates the establishment of a traceable reference full metrology chain for aspherical and freeform optical surfaces with small amplitudes.
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BACKGROUND: One of the biggest challenges in the swine industry is to increase female reproductive efficiency. Recently, vulva score categories (VSC), assessed prior to puberty, has been proposed as an indicator trait of efficient reproductive performance in sows. The objective of this study was to validate the use of VSC as an indicator trait for reproductive performance, and to perform genetic and genomic analyses for VSC. METHODS: The phenotypic relationship of VSC, using a three-point scale: small (VSC-S), medium (VSC-M), and large (VSC-L), on reproductive performance was evaluated on three farms. VSC was measured at 15 weeks of age, for farms 1 and 2, and at 14 weeks of age for farm 3 on 3981 Yorkshire gilts, in which 1083 had genotypes (~ 50 K SNPs). Genetic parameters for VSC with reproductive traits were estimated using ssGBLUP. A Genome-wide association study (GWAS) for VSC was performed using BayesB. RESULTS: For the phenotypic analysis of VSC across datasets, differences in performance were identified there was a significant effect (P ≤ 0.05) for the interaction between Farm and VSC for total number dead (TND), and a trend (P < 0.10) for total number born (TNB). There were significant (P ≤ 0.05) pre-defined contrasts of VSC-S versus VSC-M + L on TNB, number born alive (NBA), TND, number of stillborn (NSB), and number of mummies (MUM). Heritability estimates for VSC as a categorical trait (VSCc) and a quantitative trait (VSCq) were 0.40 ± 0.02 and 0.83 ± 0.02, respectively, for across farm, 0.13 ± 0.07 and 0.20 ± 0.10, respectively, for Farm1, 0.07 ± 0.07 and 0.09 ± 0.09, respectively, for Farm2, and 0.20 ± 0.03 and 0.34 ± 0.05, respectively, for Farm3. For across farms, favorable genetic correlations estimates were found for TNB (0.28 ± 0.19) and NBA (0.26 ± 0.17). Within farms, moderate genetic correlations between VSC with reproductive traits were found for TNB (0.61 ± 0.47) and MUM (0.69 ± 0.47) for farm 1, for number of services until first farrow (NS; 0.69 ± 0.38) and unique service with successful first farrow (SFS; - 0.71 ± 0.38) for farm 3. Multiple genomic regions associated with VSCc were identified. Of these, a QTL located on chromosome 3 at 33-34 Mb accounted for about 7.1% of the genetic variance for VSCc and VSCq. This region harbors the gene PRM1 that has been associated with early embryonic development in pigs. CONCLUSIONS: The results support potential of VSC for improved reproductive efficiency on first-parity performance, but the results might depend on the interaction between environmental factors and VSC, as well as potentially additive genetics.