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| 4. |
- Anney, R. J. L., et al.
(författare)
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Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
- 2017
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Ingår i: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
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| 5. |
- Binotti, M, et al.
(författare)
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Heart rate assessment using NeoTapAdvancedSupport: a simulation study
- 2019
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 104:4, s. F440-F442
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Tidskriftsartikel (refereegranskat)abstract
- NeoTapAdvancedSupport (NeoTapAS) is a mobile application, based on a screen tapping method that calculates the heart rate (HR). We aimed to evaluate the accuracy of NeoTapAS in reliably determining HR from auscultation in a high-fidelity simulated newborn resuscitation scenario.MethodsPaediatric residents assessed HR by auscultation plus NeoTapAS in an asphyxiated term infant scenario and orally communicated the estimated HR. An external observer simultaneously documented the actual HR set in the manikin and the communicated HR.ResultsOne hundred and sixty HR measurements were recorded. The agreement between communicated and set HR was good (Cohen’s kappa 0.80, 95% CI 0.72 to 0.87; Bangdiwala’s weighted agreement strength statistic 0.93). Bland-Altman plot showed a mean difference between communicated and set HR values of 1 beats per minute (bpm) (95% agreement limits −9 to 11 bpm).ConclusionNeoTapAS showed a good accuracy in estimating HR and it could be an important resource in settings with limited availability of ECG monitor.
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| 7. |
- Buselli, Irene, et al.
(författare)
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Natural language processing for aviation safety : Extracting knowledge from publicly-available loss of separation reports
- 2022
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Ingår i: Open Research Europe. - : F1000 Research Ltd. - 2732-5121. ; , s. 1-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: The air traffic management (ATM) system has historicallycoped with a global increase in traffic demand ultimately leading toincreased operational complexity.When dealing with the impact of this increasing complexity on systemsafety it is crucial to automatically analyse the losses of separation(LoSs) using tools able to extract meaningful and actionableinformation from safety reports.Current research in this field mainly exploits natural languageprocessing (NLP) to categorise the reports,with the limitations that theconsidered categories need to be manually annotated by experts andthat general taxonomies are seldom exploited.Methods: To address the current gaps,authors propose to performexploratory data analysis on safety reports combining state-of-the-arttechniques like topic modelling and clustering and then to develop analgorithm able to extract the Toolkit for ATM Occurrence Investigation(TOKAI) taxonomy factors from the free-text safety reports based onsyntactic analysis.TOKAI is a tool for investigation developed by EUROCONTROL and itstaxonomy is intended to become a standard and harmonisedapproach to future investigations.Results: Leveraging on the LoS events reported in the publicdatabases of the Comisi n de Estudio y An lisis de Notificaciones deIncidentes de Tr nsito A reo and the United Kingdom AirproxBoard,authors show how their proposal is able to automaticallyextract meaningful and actionable information from safetyreports,other than to classify their content according to the TOKAItaxonomy.The quality of the approach is also indirectly validated by checking theconnection between the identified factors and the main contributor ofthe incidents.Conclusions: Authors' results are a promising first step toward the fullautomation of a general analysis of LoS reports supported by resultson real-world data coming from two different sources.In the future,authors' proposal could be extended to othertaxonomies or tailored to identify factors to be included in the safetytaxonomies.KeywordsATM, Safety, Resilience, Natural Language Processing, Losses ofSeparation, Safety Reports, TOKAI
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| 11. |
- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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| 12. |
- Dempsey, Tina, et al.
(författare)
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Endotracheal intubation performance at a large obstetric hospital delivery room, Hanoi, Vietnam
- 2022
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Ingår i: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Intrapartum-related events account for nearly 700,000 neonatal deaths globally yearly. Endotracheal intubation is a cornerstone in preventing many of these deaths, but it is a difficult skill to acquire. Previous studies have described intubation performances in high-income coun-tries, but data from low-and middle-income countries are lacking. We aimed to assess the performance of delivery room intubation in a lower middle -income country.Methods: This prospective observational study was conducted at the Phu San Hanoi Hospital, Vietnam, from September 2020 to January 2021. Video cameras were positioned above the resuscitation tables and data were extracted using adopted software (NeoTapAS). All neonates requiring positive pressure ventilation were included. Our main variables of interest were time to first intubation attempt, first intubation attempt duration, and successful first intubation attempt.Results: 18,107 neonates were born during the five months. Of these, 75 (0.4%) received positive pressure ventilation, and 36 (0.2%) required endotracheal intubation of whom 24 were captured on video. The median time to the first intubation attempt was 252 seconds (range 91-771 sec-onds), the median first attempt duration was 49 seconds (range 10-105 seconds), and the first attempt success rate was 75%.Conclusion: Incidences of positive pressure ventilation and endotracheal intubation were low in comparison to global estimates. Three out of four intubations were successful at the first attempt and the procedural duration was often longer than recommended. Future studies should focus on how to achieve and maintain intubation skills and could include considering alternative devices for airway management at birth.
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| 13. |
- Dempsey, Tina, et al.
(författare)
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Incidence of Intrapartum-Related Events at the Largest Obstetric Hospital in Hanoi, Vietnam : A Retrospective Study
- 2022
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Ingår i: Children. - : MDPI AG. - 2227-9067. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Every year, 2.4 million neonates die during their first month of life and even more suffer permanent injury. The main causes are intrapartum-related events, prematurity, and infection, with sub-Saharan Africa and southern Asia being the worst affected regions. With a focus on intrapartum-related events, we aimed to assess the neonatal demographic characteristics, clinical management, and outcomes among neonates born at the largest obstetric hospital in Hanoi, Vietnam. This was a retrospective cross-sectional study that included all the inborn neonates in November 2019, which was selected as a representative month. A total of 4554 neonates were born during the study period. Of these, 1.0% (n = 44) were stillbirths, 0.15% (n = 7) died in hospital, 0.61% (n = 28) received positive pressure ventilation at birth, and 0.15% (n = 7) were diagnosed with hypoxic ischemic encephalopathy. A total of 581 (13%) neonates were admitted to the neonatal unit, among which the most common diagnoses were prematurity (37%, n = 217) and infection (15%, n = 89). Except for the intrapartum-related events, our findings are consistent with the previously documented data on neonatal morbidity. The intrapartum-related events, however, were surprisingly low in number even in comparison to high-income countries. Research on the current clinical practice at Phu San Hanoi Hospital may bring further clarity to identify the success factors.
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| 17. |
- Hellden, D, et al.
(författare)
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Neonatal resuscitation practices in Uganda: a video observational study
- 2021
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Ingår i: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 5:1, s. e001092-
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Tidskriftsartikel (refereegranskat)abstract
- Neonatal mortality, often due to birth asphyxia, remains stubbornly high in sub-Saharan Africa. Guidelines for neonatal resuscitation, where achieving adequate positive pressure ventilation (PPV) is key, have been implemented in low-resource settings. However, the actual clinical practices of neonatal resuscitation have rarely been examined in these settings. The primary aim of this prospective observational study was to detail the cumulative proportion of time with ventilation during the first minute on the resuscitation table of neonates needing PPV at the Mulago National Referral Hospital in Kampala, Uganda.MethodsFrom November 2015 to January 2016, resuscitations of non-breathing neonates by birth attendants were video-recorded using motion sensor cameras. The resuscitation practices were analysed using the application NeoTapAS and compared between those taking place in the labour ward and those in theatre through Fisher’s exact test and Wilcoxon rank-sum test.ResultsFrom 141 recorded resuscitations, 99 were included for analysis. The time to initiation of PPV was 66 (42–102) s overall, and there was minimal PPV during the first minute in both groups with 0 (0–10) s and 0 (0–12) s of PPV, respectively. After initiating PPV the overall duration of interruptions during the first minute was 28 (18–37) s. Majority of interruptions were caused by stimulation (28%), unknown reasons (25%) and suction (22%).ConclusionsOur findings show a low adherence to standard resuscitation practices in 2015–2016. This emphasises the need for continuous educational efforts and investments in staff and adequate resources to increase the quality of clinical neonatal resuscitation practices in low-resource settings.
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| 18. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 19. |
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| 20. |
- Hook, SM, et al.
(författare)
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Smartphone app for neonatal heart rate assessment: an observational study
- 2020
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Ingår i: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 4:1, s. e000688-
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Tidskriftsartikel (refereegranskat)abstract
- Heart rate (HR) assessment is crucial in neonatal resuscitation, but pulse oximetry (PO) and electrocardiography (ECG) are rarely accessible in low-resource to middle-resource settings. This study evaluated a free-of-charge smartphone application, NeoTap, which records HR with a screen-tapping method bypassing mental arithmetic calculations.MethodsThis observational study was carried out during three time periods between May 2015 and January 2019 in Uganda in three phases. In phase 1, a metronome rate (n=180) was recorded by low-end users (midwives) using NeoTap. In phase 2, HR (n=69) in breathing neonates was recorded by high-end users (paediatricians) using NeoTap versus PO. In phase 3, HR (n=235) in non-breathing neonates was recorded by low-end users using NeoTap versus ECG.ResultsIn high-end users the mean difference was 3 beats per minute (bpm) higher with NeoTap versus PO (95% agreement limits −14 to 19 bpm), with acquisition time of 5 seconds. In low-end users, the mean difference was 6 bpm lower with NeoTap versus metronome (95% agreement limits −26 to 14 bpm) and 3 bpm higher with NeoTap versus ECG in non-breathing neonates (95% agreement limits −48 to 53 bpm), with acquisition time of 2.7 seconds. The agreement between NeoTap and ECG was good in the HR categories of 60–99 bpm and ≥100 bpm; HR <60 bpm had few measurements (kappa index 0.71, 95% CI 0.63 to 0.79).ConclusionHR could be accurately and rapidly assessed using a smartphone application in breathing neonates in a low-resource setting. Clinical assessment by low-end users was less accurate with wider CI but still adds clinically important information in non-breathing neonates. The authors suggest low-end users may benefit from auscultation-focused training. More research is needed to evaluate its feasibility in clinical use.
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| 21. |
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| 22. |
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| 23. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 24. |
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| 25. |
- Koul, A., et al.
(författare)
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BRCA1 and BRCA2 mutations in ovarian cancer : Covariation with specific cytogenetic features
- 2000
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 10:4, s. 289-295
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed 37 primary invasive carcinomas for BRCA1 and BRCA2 mutations by screening the entire coding regions of both genes. Seven predicted truncating mutations (four in BRCA1 and three in BRCA2) and one novel BRCA1 missense variant (S1542C) were identified (8/37, 22%). Two of the BRCA1 mutations were somatic changes, whereas the remaining three BRCA1 changes and all mutations of BRCA2 were found to be of germline origin. All eight BRCA-positive tumors were serous or seropapillary carcinomas (8/27 serous tumors, 30%), and all but one were poorly differentiated. The correlation between tumor karyotype and BRCA status showed that clonal chromosomal aberrations were present in all BRCA-positive tumors (8/8) compared with 20 of 29 BRCA-negative ones. The most consistently affected region in BRCA-positive tumors was the long arm of chromosome 6; alterations within this arm with a breakpoint in band 6q21 were seen in four of five BRCA1-positive and in two of three BRCA2-positive tumors, but only in four of 20 karyotypically abnormal tumors without BRCA mutations, suggesting that the genetic pathways of tumor progression differ in the two groups. The high frequency of germline BRCA mutations detected in this pilot study (16% of 37 invasive carcinomas) points to the need for more extended analyses of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population.
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| 26. |
- Koul, Anjila, et al.
(författare)
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Identification of TP53 gene mutations in uterine corpus cancer with short follow-up
- 1997
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 67:3, s. 295-302
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Tidskriftsartikel (refereegranskat)abstract
- The involvement of the TP53 tumor suppressor gene in uterine corpus cancer was investigated by single-stranded conformation polymorphism and sequence analysis of its exons 4 to 10. Mutations were found in 12 (18.5%) of 65 cases. Ten of these 12 were single-base substitutions (8 missense and 2 nonsense mutations), whereas 2 were frame-shifting mutations. TP53 gene mutations correlated significantly with advanced surgical stage of disease (P = 0.006) and unfavorable tumor histology types (P = 0.003), whereas the association to myometrial wall invasion did not reach statistical significance (P = 0.054). TP53 gene mutations also correlated significantly with allelic loss at TP53 locus (P = 0.024), absence of estrogen (P = 0.045) and progesterone receptors (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction values (P = 0.002). Our results suggest that inactivation of the TP53 checkpoint function is associated with disease transition into a stage of rapid progression and spread.
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| 27. |
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| 28. |
- Larsson, M., et al.
(författare)
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Oxygen saturation after birth in resuscitated neonates in Uganda: a video-based observational study
- 2022
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Ingår i: Bmj Paediatrics Open. - : BMJ. - 2399-9772. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Monitoring of peripheral capillary oxygen saturation (SpO(2)) during neonatal resuscitation is standard of care in high-resource settings, but seldom performed in low-resource settings. We aimed to measure SpO(2) and heart rate during the first 10 min of life in neonates receiving positive pressure ventilation (PPV) according to the Helping Babies Breathe (HBB) protocol and compare results with SpO(2) and heart rate targets set by the American Heart Association (AHA). Methods A cross-sectional study was conducted at Mulago National Referral Hospital, Kampala, Uganda, as a substudy of the NeoSupra Trial. SpO(2) and heart rate were measured on apnoeic neonates (>= 34 weeks) who received PPV according to HBB (room air). Those who remained distressed after PPV received supplemental oxygen (O-2). All resuscitations were video recorded and data were extracted by video review at 1 min intervals until 10 min post partum. Data were analysed for all observations and separately for only observations before and during PPV. Results 49 neonates were analysed. Median SpO(2) at 5 min (n=39) was 67% (49-88) with 59% of the observations below AHA target of 80%. At 10 min median SpO(2) (n=44) was 93% (80-97) and 32% were below AHA target of 85%. When only observations before and during PPV were analysed, median SpO(2) min (n=18) was 52% (34-66) and 83% were below AHA target. At 10 min (n=15), median SpO(2) was 72% (57-89) and 67% were below AHA target. Median heart rates were above AHA target of 100 beats/min at all time intervals. Conclusions A high proportion of neonates resuscitated with PPV after birth failed to reach the AHA SpO(2) target in this small sample, implying an increased risk of hypoxic-ischaemic encephalopathy. Further studies in low-resource settings are needed to evaluate baseline data and the need for supplemental O-2 and optimal SpO(2) during PPV.
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| 29. |
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| 30. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 31. |
- Lu, Yingchang, et al.
(författare)
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A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
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Tidskriftsartikel (refereegranskat)abstract
- .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
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| 32. |
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| 33. |
- Olson, L, et al.
(författare)
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Neonatal resuscitation monitoring: A low-cost video recording setup for quality improvement in the delivery room at the resuscitation table
- 2022
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Ingår i: Frontiers in pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10, s. 952489-
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Tidskriftsartikel (refereegranskat)abstract
- The quality of neonatal resuscitation after delivery needs to be improved to reach the Sustainable Development Goals 3.2 (reducing neonatal deaths to <12/1,000 live newborns) by the year 2030. Studies have emphasized the importance of correctly performing the basic steps of resuscitation including stimulation, heart rate assessment, ventilation, and thermal control. Recordings with video cameras have previously been shown to be one way to identify performance practices during neonatal resuscitation.MethodsA description of a low-cost delivery room set up for video recording of neonatal resuscitation. The technical setup includes rechargeable high-definition cameras with two-way audio, NeoBeat heart rate monitors, and the NeoTapAS data collection tools for iPad with direct data export of data for statistical analysis. The setup was field tested at Mulago National Referral Hospital, Kampala, Uganda, and Phu San Hanoi Hospital, Hanoi, Vietnam.ResultsThe setup provided highly detailed resuscitation video footage including data on procedures and team performance, heart rate monitoring, and clinical assessment of the neonate. The data were analyzed with the free-of-charge NeoTapAS for iPad, which allowed fast and accurate registration of all resuscitative events. All events were automatically registered and exported to R statistical software for further analysis.ConclusionsVideo analysis of neonatal resuscitation is an emerging quality assurance tool with the potential to improve neonatal resuscitation outcomes. Our methodology and technical setup are well adapted for low- and lower-middle-income countries settings where improving neonatal resuscitation outcomes is crucial. This delivery room video recording setup also included two-way audio communication that potentially could be implemented in day-to-day practice or used with remote teleconsultants.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Pejovic, NJ, et al.
(författare)
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Neonatal resuscitation using a laryngeal mask airway: a randomised trial in Uganda
- 2018
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Ingår i: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 103:3, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Mortality rates from birth asphyxia in low-income countries remain high. Face mask ventilation (FMV) performed by midwives is the usual method of resuscitating neonates in such settings but may not always be effective. The i-gel is a cuffless laryngeal mask airway (LMA) that could enhance neonatal resuscitation performance. We aimed to compare LMA and face mask (FM) during neonatal resuscitation in a low-resource setting.SettingMulago National Referral Hospital, Kampala, Uganda.DesignThis prospective randomised clinical trial was conducted at the labour ward operating theatre. After a brief training on LMA and FM use, infants with a birth weight >2000 g and requiring positive pressure ventilation at birth were randomised to resuscitation by LMA or FM. Resuscitations were video recorded.Main outcome measuresTime to spontaneous breathing.ResultsForty-nine (24 in the LMA and 25 in the FM arm) out of 50 enrolled patients were analysed. Baseline characteristics were comparable between the two arms. Time to spontaneous breathing was shorter in LMA arm than in FM arm (mean 153 s (SD±59) vs 216 s (SD±92)). All resuscitations were effective in LMA arm, whereas 11 patients receiving FM were converted to LMA because response to FMV was unsatisfactory. There were no adverse effects.ConclusionA cuffless LMA was more effective than FM in reducing time to spontaneous breathing. LMA seems to be safe and effective in clinical practice after a short training programme. Its potential benefits on long-term outcomes need to be assessed in a larger trial.Clinical trial registryThis trial was registered in https://clinicaltrials.gov, with registration number NCT02042118.
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- Pejovic, Tanja, et al.
(författare)
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Chromosome aberrations in 35 primary ovarian carcinomas
- 1992
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 4:1, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic analysis was performed on short-term cultures of primary ovarian carcinomas from 62 patients. Cytogenetic analysis was successful in 59 cases. Clonal chromosome aberrations were detected in 35 tumors. Only numerical changes or a single structural change were found in five carcinomas: trisomy 12 was the sole anomaly in two tumors, one tumor had the karyotype 50,XX, + 5, + 7, + 12, + 14, a fourth tumor had a balanced t(1;5), and the fifth tumor had an unbalanced t(8;15). The fact that four of these five carcinomas were well differentiated suggests that simple karyotypic changes are generally characteristic of these less aggressive ovarian tumors. The majority of the cytogenetically abnormal tumors (n = 30) had complex karyotypes, with both numerical and structural aberrations and often hypodiploid or near-triploid stemlines. The numerical imbalances (comparison with the nearest euploid number) were mostly losses, in order of decreasing frequency -17, -22, -13, -8, -X, and -14. The structural aberrations were mostly deletions and unbalanced translocations. Recurrent loss of genetic material affected chromosome arms 1p, 3p, 6q, and 11p. The breakpoints of the clonal structural abnormalities clustered to several chromosome bands and segments: 19p13, 11p13-15, 1q21-23, 1p36, 19q13, 3p12-13, and 6q21-23. The most consistent change (16 tumors) was a 19p + marker, and in 12 of the tumors the 19p + markers looked alike.
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- Tanner, M M, et al.
(författare)
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Genetic aberrations in hypodiploid breast cancer: frequent loss of chromosome 4 and amplification of cyclin D1 oncogene
- 1998
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Ingår i: American Journal of Pathology. - 1525-2191. ; 153:1, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of somatic genetic aberrations in breast cancer has remained poorly understood. The most common chromosomal abnormality is hyperdiploidy, which is thought to arise via a transient hypodiploid state. However, hypodiploidy persists in 1 to 2% of breast tumors, which are characterized by a poor prognosis. We studied the genetic aberrations in 15 flow cytometrically hypodiploid breast cancers by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). Surprisingly, numerous copy number gains were detected in addition to the copy number losses. The number of gains per tumor was 4.3 +/- 3.2 and that of losses was 4.5 +/- 3.3 (mean +/- SD), which is similar to that previously observed in hyperdiploid breast cancers. Gains at chromosomes or chromosomal regions at 11q13, 1q, 19, and 16p and losses of 2q, 4, 6q, 9p, 13, and 18 were most commonly observed. Compared with unselected breast carcinomas, hypodiploid tumors showed certain differences. Loss of chromosome 4 (53%) and gain of 11q13 (60%) were significantly more common in hypodiploid tumors. The gain at 11q13 was found by FISH to harbor amplification of the Cyclin D1 oncogene, which is therefore three to four times more common in hypodiploid than in unselected breast cancers (15 to 20%). Structural chromosomal aberrations (such as Cyclin D1 amplification) were present both in diploid and hypodiploid tumor cell populations, as assessed by FISH and CGH after flow cytometric sorting. Together these results indicate that hypodiploid tumors form a distinct genetic entity of invasive breast cancer, although they probably share a common genetic evolution pathway where structural chromosomal aberrations precede gross DNA ploidy changes.
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