Abstract Intracranial aneurysms are acquired lesions (5–10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact ...etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3–p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3–p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2 gene). Moreover, 3 of the polymorphisms analyzed in 2 genes (endothelial nitric oxide synthase T786C, interleukin-6 G572C, and interleukin-6 G174C) were found to be significantly associated with ruptured/unruptured aneurysms: the endothelial nitric oxide synthase gene single-nucleotide polymorphisms increased the risk, while IL-6 G174C seemed protective. More recently, two genomic loci (endothelin receptor A and cyclin-dependent kinase inhibitor 2BAS) have been found to be significantly associated with intracranial aneurysms in the Japanese population; endothelin-1 is a potent vasoconstrictor produced by the endothelial cells. Until now, there are no diagnostic tests for specific genetic risk factors to identify patients who are at a high risk of developing intracranial aneurysms. Knowledge of the genetic determinants may be useful in order to allow clues on stopping aneurysm formation and obtain diagnostic tools for identifying individuals at increased risk. Further multicenter studies have to be carried out.
•Aside from transvaginal ultrasound (TVS) there was a paucity of data to assess other imaging modalities for the diagnosis of bladder deep endometriosis.•TVS had limited sensitivity but excellent ...specificity.
To review the diagnostic accuracy and determine the optimum imaging modality for the detection of bladder deep endometriosis (DE) in women with a clinical suspicion of endometriosis.
A systematic review of studies published from inception to May 2020 using Embase, Google Scholar, Medline, PubMed and Scopus. Prospective studies, which pre-operatively assessed any imaging modality for the presence of bladder DE, and correlated with the gold standard surgical data as a reference were included. The QUADAS-2 tool was used to assess quality. This review was prospectively registered with PROSPERO (CRD42017059872).
Of the 1,977 references identified, 8 studies (n = 1,052) were included in the analysis. The overall pooled sensitivity and specificity, from which the likelihood ratio of a positive test (LR+), likelihood ratio of a negative test (LR-) and diagnostic odds ratio (DOR) were calculated, for all transvaginal ultrasonography (TVS) techniques were 55 % (95 % CI 28–79%), 99 % (95 % CI 98–100%), 54.5 (95 % CI 18.9–157.4), 0.46 (95 % CI 0.25 – 0.85) and 119 (95 % CI 24–577), and for only two-dimensional (2D) TVS 53 % (95 % CI 23–82%), 99 % (96 % CI 97–100%), 48.8 (95 % CI 13.1–181.4), 0.47 (95 % CI 0.23 – 0.98), and 104 (95 % CI 15–711), respectively. Meta-analyses of the other modalities, namely magnetic resonance imaging (MRI) and transrectal endoscopic sonography (RES), were not possible due to the limited number of studies. There was significant heterogeneity and the studies were considered poor methodologically according to the QUADAS-2 tool.
Whilst the sensitivity of TVS was limited, the specificity was excellent. Given that there is a paucity of literature for other imaging modalities, until more studies are performed, TVS should be considered as the first-line tool given it is the only modality with sufficient evidence.
Novel sequencing technologies are rapidly expanding the size of data sets that can be applied to phylogenetic studies. Currently the most commonly used phylogenomic approaches involve some form of ...genome reduction. While these approaches make assembling phylogenomic data sets more economical for organisms with large genomes, they reduce the genomic coverage and thereby the long-term utility of the data. Currently, for organisms with moderate to small genomes (<1000 Mbp) it is feasible to sequence the entire genome at modest coverage (10–30×). Computational challenges for handling these large data sets can be alleviated by assembling targeted reads, rather than assembling the entire genome, to produce a phylogenomic data matrix. Here we demonstrate the use of automated Target Restricted Assembly Method (aTRAM) to assemble 1107 single-copy ortholog genes from whole genome sequencing of sucking lice (Anoplura) and out-groups. We developed a pipeline to extract exon sequences from the aTRAM assemblies by annotating them with respect to the original target protein. We aligned these protein sequences with the inferred amino acids and then performed phylogenetic analyses on both the concatenated matrix of genes and on each gene separately in a coalescent analysis. Finally, we tested the limits of successful assembly in aTRAM by assembling 100 genes from close- to distantly related taxa at high to low levels of coverage. Both the concatenated analysis and the coalescent-based analysis produced the same tree topology, which was consistent with previously published results and resolved weakly supported nodes. These results demonstrate that this approach is successful at developing phylogenomic data sets from raw genome sequencing reads. Further, we found that with coverages above 5–10×, aTRAM was successful at assembling 80–90% of the contigs for both close and distantly related taxa. As sequencing costs continue to decline, we expect full genome sequencing will become more feasible for a wider array of organisms, and aTRAM will enable mining of these genomic data sets for an extensive variety of applications, including phylogenomics.
Objective
To assess the general population’s knowledge regarding the utility and availability of tools to diagnosis endometriosis, with a focus on ultrasound.
Design
An international cross‐sectional ...online survey study was performed between August and October 2019.
Setting and population
5301 respondents, representing 73 countries.
Methods
In all, 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient‐ and community‐endometriosis groups using social media.
Main outcomes and measures
Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound.
Results
In all, 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of whom had been diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. A total of 91.8%, 28.8% and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method, whereas in those diagnosed non‐surgically, 51.5% knew (P < 0.001). In all, 14.7%, 31.1% and 18.2% stated superficial, ovarian and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). Lastly, 58.4% of respondents do not believe they could access an advanced ultrasound in their region.
Conclusions
There is a limited appreciation for the role of non‐surgical diagnostic tests for endometriosis among lay respondents to this survey.
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International survey shows limited awareness of lay respondents about non‐surgical endometriosis diagnostic tools.
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International survey shows limited awareness of lay respondents about non‐surgical endometriosis diagnostic tools.
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