Bias in Zipf's Law Estimators

The prevailing maximum likelihood estimators for inferring power law models from rank-frequency data are biased. The source of this bias is an inappropriate likelihood function. The correct likelihood function is derived and shown to be computationally intractable. A more computationally efficient method of approximate Bayesian computation (ABC) is explored. This method is shown to have less bias for data generated from idealised rank-frequency Zipfian distributions. However, the existing estimators and the ABC estimator described here assume that words are drawn from a simple probability distribution, while language is a much more complex process. We show that this false assumption leads to continued biases when applying any of these methods to natural language to estimate Zipf exponents. We recommend that researchers be aware of these biases when investigating power laws in rank-frequency data.Comment: 15 pages, 11 figure

Diagnostic performance of quantitative coronary artery disease assessment using computed tomography in patients with aortic stenosis undergoing transcatheter aortic-valve implantation.

BACKGROUND Computed tomography angiography (CTA) is a cornerstone in the pre- transcatheter aortic valve replacement (TAVI) assessment. We evaluated the diagnostic performance of CTA and coronary artery calcium score (CACS) for CAD evaluation compared to invasive coronary angiography in a cohort of TAVI patients. METHODS In consecutive TAVI patients without prior coronary revascularization and device implants, CAD was assessment by quantitative analysis in CTA. (a) Patients with non-evaluable segments were classified as obstructive CAD. (b) In patients with non-evaluable segments a CACS cut-off of 100 was applied for obstructive CAD. The reference standard was quantitative invasive coronary angiography (QCA, i.e. ≥ 50% stenosis). RESULTS 100 consecutive patients were retrospectively included, age was 82.3 ± 6.5 years and 30% of patients had CAD. In 16% of the patients, adequate visualization of the entire coronary tree (all 16 segments) was possible with CTA, while 84% had at least one segment which was not evaluable for CAD analysis due to impaired image quality. On a per-patient analysis, where patients with low image quality were classified as CAD, CTA showed a sensitivity of 100% (95% CI 88.4-100.0), specificity of 11.4% (95% CI 5.1-21.3), PPV of 32.6% (95% CI 30.8-34.5), NPV of 100% and diagnostic accuracy of 38% (95% CI 28.5-48.3) for obstructive CAD. When applying a combined approach of CTA (in patients with good image quality) and CACS (in patients with low image quality), the sensitivity and NPV remained at 100% and obstructive CAD could be ruled out in 20% of the TAVI patients, versus 8% using CTA alone. CONCLUSION In routinely acquired pre-TAVI CTA, the image quality was insufficient in a high proportion of patients for the assessment of the entire coronary artery tree. However, when adding CACS in patients with low image quality to quantitative CTA assessment in patients with good image quality, obstructive CAD could be ruled-out in 1/5 of the patients and may therefore constitute a strategy to streamline pre-procedural workup, and reduce risk, radiation and costs in selected TAVI patients without prior coronary revascularization or device implants

Reproducibility of 4D cardiac computed tomography feature tracking myocardial strain and comparison against speckle-tracking echocardiography in patients with severe aortic stenosis.

BACKGROUND Myocardial strain is an established parameter for the assessment of cardiac function and routinely derived from speckle tracking echocardiography (STE). Novel post-processing tools allow deformation imaging also by 4D cardiac computed tomography angiography (CCT). This retrospective study aims to analyze the reproducibility of CCT strain and compare it to that of STE. METHODS Left (LV) and right ventricular (RV), and left atrial (LA) ejection fraction (EF), dimensions, global longitudinal (GLS), circumferential (GCS) and radial strain (GRS) were determined by STE and CCT feature tracking in consecutive patients with severe aortic stenosis evaluated for transcatheter aortic valve implantation. RESULTS 106 patients (mean age 79.9 ​± ​7.8, 44.3% females) underwent CCT at a median of 3 days (IQR 0-28 days) after STE. In CCT, strain measures showed good to excellent reproducibility (intra- and inter-reader intraclass correlation coefficient ≥0.75) consistently in the LV, RV and LA. In STE, only LV GLS and LA GLS yielded good reproducibility, whereas LV GCS and LV GRS showed moderate, and RV GLS and free wall longitudinal strain (FWLS) poor reproducibility. Agreement between CCT and STE was strong for LV GLS only, while other strain features displayed moderate (LV GCS, LA GLS) or weak (LV GRS, RV GLS and FWLS) inter-modality correlation. CONCLUSION LV, RV and LA CCT strain assessments were highly reproducible. While a strong agreement to STE was found for LV GLS, inter-modality correlation was moderate or weak for LV GCS, LV GRS, and RV and LA longitudinal strain, possibly related to poor reproducibility of STE measurements

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

Background Microvascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE. Methods Patients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort. Results Forty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%. Conclusion Segmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI

Mio-Pliocene Faunal Exchanges and African Biogeography: The Record of Fossil Bovids

The development of the Ethiopian biogeographic realm since the late Miocene is here explored with the presentation and review of fossil evidence from eastern Africa. Prostrepsiceros cf. vinayaki and an unknown species of possible caprin affinity are described from the hominid-bearing Asa Koma and Kuseralee Members (∼5.7 and ∼5.2 Ma) of the Middle Awash, Ethiopia. The Middle Awash Prostrepsiceros cf. vinayaki constitutes the first record of this taxon from Africa, previously known from the Siwaliks and Arabia. The possible caprin joins a number of isolated records of caprin or caprin-like taxa recorded, but poorly understood, from the late Neogene of Africa. The identification of these two taxa from the Middle Awash prompts an overdue review of fossil bovids from the sub-Saharan African record that demonstrate Eurasian affinities, including the reduncin Kobus porrecticornis, and species of Tragoportax. The fossil bovid record provides evidence for greater biological continuity between Africa and Eurasia in the late Miocene and earliest Pliocene than is found later in time. In contrast, the early Pliocene (after 5 Ma) saw the loss of any significant proportions of Eurasian-related taxa, and the continental dominance of African-endemic taxa and lineages, a pattern that continues today

Signal transduction in a covalent post-assembly modification cascade

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels–Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels–Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes

A 4-item PRECISE-DAPT score for dual antiplatelet therapy duration decision-making

The originally-proposed PRECISE-DAPT score is a 5-item risk score supporting decision-making for dual antiplatelet therapy1 duration after PCI. It is unknown if a simplified version of the score based on 4 factors (age, hemoglobin, creatinine clearance, prior bleeding), and lacking white-blood cell count, retains potential to guide DAPT duration. The 4-item PRECISE-DAPT was used to categorize 10,081 patients who were randomized to short (3-6 months) or long (12-24 months) DAPT regimen according to high (HBR defined by PRECISE-DAPT ≥25 points) or non-high bleeding risk (PRECISE-DAPT<25) status. Long treatment duration was associated with higher bleeding rates in HBR (ARD +2.22% [95% CI +0.53 to +3.90]) but not in non-HBR patients (ARD +0.25% [−0.14 to +0.64]; pint = 0.026), and associated with lower ischemic risks in non-HBR (ARD −1.44% [95% CI −2.56 to −0.31]), but not in HBR patients (ARD +1.16% [−1.91 to +4.22]; pint = 0.11). Only non-HBR patients experienced lower net clinical adverse events (NACE) with longer DAPT (pint = 0.043). A 4-item simplified version of the PRECISE-DAPT score retains the potential to categorize patients who benefit from prolon

Recognition of depression in people of different cultures: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Many minority group patients who attend primary health care are depressed. To identify a depressive state when GPs see patients from other cultures than their own can be difficult because of cultural and gender differences in expressions and problems of communication. The aim of this study was to explore and analyse how GPs think and deliberate when seeing and treating patients from foreign countries who display potential depressive features.</p> <p>Methods</p> <p>The data were collected in focus groups and through individual interviews with GPs in northern Sweden and analysed by qualitative content analysis.</p> <p>Results</p> <p>In the analysis three themes, based on various categories, emerged; "Realizing the background", "Struggling for clarity" and "Optimizing management". Patients' early life events of importance were often unknown which blurred the accuracy. Reactions to trauma, cultural frictions and conflicts between the new and old gender norms made the diagnostic process difficult. The patient-doctor encounter comprised misconceptions, and social roles in the meetings were sometimes confused. GPs based their judgement mainly on clinical intuition and the established classification of depressive disorders was discussed. Tools for management and adequate action were diffuse.</p> <p>Conclusion</p> <p>Dialogue about patients' illness narratives and social context are crucial. There is a need for tools for multicultural, general practice care in the depressive spectrum. It is also essential to be aware of GPs' own conceptions in order to avoid stereotypes and not to under- or overestimate the occurrence of depressive symptoms</p

Determination of “borderline resectable” pancreatic cancer – A global assessment of 30 shades of grey

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis. Accurate preoperative assessment using computed tomography (CT) to determine resectability is crucial in ensuring patients are offered the most appropriate therapeutic strategy. Despite the use of classification guidelines, any interobserver variability between reviewing surgeons and radiologists may confound decisions influencing patient treatment pathways. Methods: In this multicentre observational study, an international group of 96 clinicians (42 hepatopancreatobiliary surgeons and 54 radiologists) were surveyed and asked to report 30 pancreatic CT scans of pancreatic cancer deemed borderline at respective multidisciplinary meetings (MDM). The degree of interobserver agreement in resectability among radiologists and surgeons was assessed and subgroup regression analysis was performed. Results: Interobserver variability between reviewers was high with no unanimous agreement. Overall interobserver agreement was fair with a kappa value of 0.32 with a higher rate of agreement among radiologists over surgeons. Conclusion: Interobserver variability among radiologists and surgeons globally is high, calling into question the consistency of clinical decision making for patients with PDAC and suggesting that central review may be required for studies of neoadjuvant or adjuvant approaches in future as well as ongoing quality control initiatives, even amongst experts in the field