Improving ICD-based semantic similarity by accounting for varying degrees of comorbidity

Finding similar patients is a common objective in precision medicine, facilitating treatment outcome assessment and clinical decision support. Choosing widely-available patient features and appropriate mathematical methods for similarity calculations is crucial. International Statistical Classification of Diseases and Related Health Problems (ICD) codes are used worldwide to encode diseases and are available for nearly all patients. Aggregated as sets consisting of primary and secondary diagnoses they can display a degree of comorbidity and reveal comorbidity patterns. It is possible to compute the similarity of patients based on their ICD codes by using semantic similarity algorithms. These algorithms have been traditionally evaluated using a single-term expert rated data set. However, real-word patient data often display varying degrees of documented comorbidities that might impair algorithm performance. To account for this, we present a scale term that considers documented comorbidity-variance. In this work, we compared the performance of 80 combinations of established algorithms in terms of semantic similarity based on ICD-code sets. The sets have been extracted from patients with a C25.X (pancreatic cancer) primary diagnosis and provide a variety of different combinations of ICD-codes. Using our scale term we yielded the best results with a combination of level-based information content, Leacock & Chodorow concept similarity and bipartite graph matching for the set similarities reaching a correlation of 0.75 with our expert's ground truth. Our results highlight the importance of accounting for comorbidity variance while demonstrating how well current semantic similarity algorithms perform.Comment: 11 pages, 6 figures, 1 tabl

The Simons Observatory: Beam characterization for the Small Aperture Telescopes

We use time-domain simulations of Jupiter observations to test and develop a beam reconstruction pipeline for the Simons Observatory Small Aperture Telescopes. The method relies on a map maker that estimates and subtracts correlated atmospheric noise and a beam fitting code designed to compensate for the bias caused by the map maker. We test our reconstruction performance for four different frequency bands against various algorithmic parameters, atmospheric conditions and input beams. We additionally show the reconstruction quality as function of the number of available observations and investigate how different calibration strategies affect the beam uncertainty. For all of the cases considered, we find good agreement between the fitted results and the input beam model within a ~1.5% error for a multipole range l = 30 - 700.Comment: 22 pages, 21 figures, to be submitted to Ap

DNAAF1 links heart laterality with the AAA+ ATPase RUVBL1 and ciliary intraflagellar transport

DNAAF1 (LRRC50) is a cytoplasmic protein required for dynein heavy chain assembly and cilia motility, and DNAAF1 mutations cause primary ciliary dyskinesia (PCD; MIM 613193). We describe four families with DNAAF1 mutations and complex congenital heart disease (CHD). In three families, all affected individuals have typical PCD phenotypes. However, an additional family demonstrates isolated CHD (heterotaxy) in two affected siblings, but no clinical evidence of PCD. We identified a homozygous DNAAF1 missense mutation, p.Leu191Phe, as causative for heterotaxy in this family. Genetic complementation in dnaaf1-null zebrafish embryos demonstrated the rescue of normal heart looping with wild-type human DNAAF1, but not the p.Leu191Phe variant, supporting the conserved pathogenicity of this DNAAF1 missense mutation. This observation points to a phenotypic continuum between CHD and PCD, providing new insights into the pathogenesis of isolated CHD. In further investigations of the function of DNAAF1 in dynein arm assembly, we identified interactions with members of a putative dynein arm assembly complex. These include the ciliary intraflagellar transport protein IFT88 and the AAA+ (ATPases Associated with various cellular Activities) family proteins RUVBL1 (Pontin) and RUVBL2 (Reptin). Co-localization studies support these findings, with the loss of RUVBL1 perturbing the co-localization of DNAAF1 with IFT88. We show that RUVBL1 orthologues have an asymmetric left-sided distribution at both the mouse embryonic node and the Kupffer’s vesicle in zebrafish embryos, with the latter asymmetry dependent on DNAAF1. These results suggest that DNAAF1-RUVBL1 biochemical and genetic interactions have a novel functional role in symmetry breaking and cardiac development

The Simons Observatory: Beam characterization for the small aperture telescopes

We use time-domain simulations of Jupiter observations to test and develop a beam reconstruction pipeline for the Simons Observatory Small Aperture Telescopes. The method relies on a mapmaker that estimates and subtracts correlated atmospheric noise and a beam fitting code designed to compensate for the bias caused by the mapmaker. We test our reconstruction performance for four different frequency bands against various algorithmic parameters, atmospheric conditions, and input beams. We additionally show the reconstruction quality as a function of the number of available observations and investigate how different calibration strategies affect the beam uncertainty. For all of the cases considered, we find good agreement between the fitted results and the input beam model within an ∼1.5% error for a multipole range ℓ = 30–700 and an ∼0.5% error for a multipole range ℓ = 50–200. We conclude by using a harmonic-domain component separation algorithm to verify that the beam reconstruction errors and biases observed in our analysis do not significantly bias the Simons Observatory r-measuremen

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Alignment of the CMS tracker with LHC and cosmic ray data

© CERN 2014 for the benefit of the CMS collaboration, published under the terms of the Creative Commons Attribution 3.0 License by IOP Publishing Ltd and Sissa Medialab srl. Any further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation and DOI.The central component of the CMS detector is the largest silicon tracker ever built. The precise alignment of this complex device is a formidable challenge, and only achievable with a significant extension of the technologies routinely used for tracking detectors in the past. This article describes the full-scale alignment procedure as it is used during LHC operations. Among the specific features of the method are the simultaneous determination of up to 200 000 alignment parameters with tracks, the measurement of individual sensor curvature parameters, the control of systematic misalignment effects, and the implementation of the whole procedure in a multi-processor environment for high execution speed. Overall, the achieved statistical accuracy on the module alignment is found to be significantly better than 10μm

Water, mining, and waste: An historical and economic perspective on conflict management in South Africa

Lack of government intervention in South Africa’s mining industry has worsened conflicts associated with limited water resources. With the advent of democracy, new legislation demands that all South African citizens have the right to a clean, safe environment, including access to potable water, and that the country develop in a sustainable manner. But conflict remains due to the historical partnership between the government and the mining industry, as well as due to cumulative impacts associated with mining, which has polluted natural ground water sources. In this article, an historical overview of the mining industry in South Africa is presented, along with a simple economic model to describe behavior of the mining industry over time. Legislative frameworks used to address mine waste and mine water management are evaluated and suggestions are made for how to use an understanding of resource driven conflict to improve the outlook of mining and access to water for all in South Africa.Water, mining, conflict, South Africa

Brain metastases in gastroesophageal cancers—an underestimated complication

Background!#!Brain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs.!##!Methods!#!We analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs.!##!Results!#!From 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%, p = 0.0051) and in adenocarcinomas (90.74% vs 9.26%, p = 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (p = 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months, p = 0.0091).!##!Conclusion!#!In this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases