Provenance of north Gondwana Cambrian-Ordovician sandstone: U-Pb SHRIMP dating of detrital zircons from Israel and Jordan

A vast sequence of quartz-rich sandstone was deposited over North Africa and Arabia during Early Palaeozoic times, in the aftermath of Neoproterozoic Pan-African orogeny and the amalgamation of Gondwana. This rock sequence forms a relatively thin sheet (1–3 km thick) that was transported over a very gentle slope and deposited over a huge area. The sense of transport indicates unroofing of Gondwana terranes but the exact provenance of the siliciclastic deposit remains unclear. Detrital zircons from Cambrian arkoses that immediately overlie the Neoproterozoic Arabian–Nubian Shield in Israel and Jordan yielded Neoproterozoic U–Pb ages (900–530 Ma), suggesting derivation from a proximal source such as the Arabian–Nubian Shield. A minor fraction of earliest Neoproterozoic and older age zircons was also detected. Upward in the section, the proportion of old zircons increases and reaches a maximum (40%) in the Ordovician strata of Jordan. The major earliest Neoproterozoic and older age groups detected are 0.95–1.1, 1.8–1.9 and 2.65–2.7 Ga, among which the 0.95–1.1 Ga group is ubiquitous and makes up as much as 27% in the Ordovician of Jordan, indicating it is a prominent component of the detrital zircon age spectra of northeast Gondwana. The pattern of zircon ages obtained in the present work reflects progressive blanketing of the northern Arabian–Nubian Shield by Cambrian–Ordovician sediments and an increasing contribution from a more distal source, possibly south of the Arabian–Nubian Shield. The significant changes in the zircon age signal reflect many hundreds of kilometres of southward migration of the provenance

Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. Design, setting, and participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. Main outcomes and measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. Conclusions and relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.Patient-Centered Outcomes Research Institute - PCOR

The detrital zircon U-Pb-Hf fingerprint of the northern Arabian-Nubian Shield as reflected by a Late Ediacaran arkosic wedge (Zenifim Formation; subsurface Israel)

The Neoproterozoic Arabian-Nubian Shield (ANS), which comprises the northern sector of the East African Orogen (EAO), has been deeply denuded in Ediacaran times and its erosional products were deposited across NE Africa and Arabia; they are also found i

Molecular targeting of papillary thyroid carcinoma with fluorescently labeled ratiometric activatable cell penetrating peptides in a transgenic murine model.

Background and objectivesMolecularly targeted fluorescent molecules may help detect tumors that are unseen by traditional white-light surgical techniques. We sought to evaluate a fluorescent ratiometric activatable cell penetrating peptide (RACPP) for tumor detection in a transgenic model of PTC.MethodsThirteen BRAFV600E mice with PTC were studied-seven injected intravenously with RACPP, four controls with saline. Total thyroidectomy was performed with microscopic white-light visualization. Fluorescent imaging of post-thyroidectomy fields was performed, and tissue with increased signal was removed and evaluated for PTC. Final samples were analyzed by a pathologist blinded to conditions. Vocal cord function was evaluated postoperatively with video laryngoscopy.ResultsThe average in situ ratiometric (Cy5/Cy7) thyroid tumor-to-background contrast ratio was 2.27 +/- 0.91. Fluorescence-guided clean-up following thyroidectomy identified additional tumor in 2 of 7 RACPP animals (smallest dimension 1.2 mm), and decreased the number of animals with residual tumor from 4 to 3. All retained tumor foci on final pathology were smaller than 0.76 mm. Intact vocal abduction was present in all of the RACPP animals.ConclusionsRACPPs successfully targeted PTC in a transgenic thyroidectomy model, and allowed for residual tumor detection that reduced positive margins beyond what was possible with white-light surgery alone

Functional disease architectures reveal unique biological role of transposable elements

Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze data from 41 independent diseases and complex traits to draw three conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39 ± 2% of heritability), TE explain substantially more heritability than expected based on their depletion for known functional annotations. This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function. Third, Short Interspersed Nuclear Elements (SINE) are far more enriched for blood traits than for other traits. Our results can help elucidate the biological roles that TE play in the genetic architecture of diseases