Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence

In adult mice, haematopoietic stem cells are maintained in a quiescent state. The transcriptional repressor Myeloid Translocation Gene 16 (MTG16) is shown to govern this process

Tidal propagation in strongly convergent channels

Simple first‐ and second‐order analytic solutions, which diverge markedly from classical views of cooscillating tides, are derived for tidal propagation in strongly convergent channels. Theoretical predictions compare well with observations from typical examples of shallow, “funnel‐shaped” tidal estuaries. A scaling of the governing equations appropriate to these channels indicates that at first order, gradients in cross‐sectional area dominate velocity gradients in the continuity equation and the friction term dominates acceleration in the momentum equation. Finite amplitude effects, velocity gradients due to wave propagation, and local acceleration enter the equations at second order. Applying this scaling, the first‐order governing equation becomes a first‐order wave equation, which is inconsistent with the presence of a reflected wave. The solution is of constant amplitude and has a phase speed near the frictionless wave speed, like a classical progressive wave, yet velocity leads elevation by 90°, like a classical standing wave. The second‐order solution at the dominant frequency is also a unidirectional wave; however, its amplitude is exponentially modulated. If inertia is finite and convergence is strong, amplitude increases along channel, whereas if inertia is weak and convergence is limited, amplitude decays. Compact solutions for second‐order tidal harmonics quantify the partially canceling effects of (1) time variations in channel depth, which slow the propagation of low water, and (2) time variations in channel width, which slow the propagation of high water. Finally, it is suggested that phase speed, along‐channel amplitude growth, and tidal harmonics in strongly convergent channels are all linked by morphodynamic feedback

Validation of a Persian version of the OIDP index

BACKGROUND: Measuring the impacts of oral conditions on quality of life is an important part of oral health needs assessment. For this purpose a variety of oral health-related quality of life instruments have been developed. To use a scale in a new context or with a different groups of people, it is necessary to re-establish its psychometric properties. The objectives of this study are to develop and test the reliability and validity of the Persian version of Oral Impacts on Daily Performances (OIDP) index. METHODS: The Persian version of OIDP index was developed through a linguistic translation exercise. The psychometric properties of the Persian version of OIDP were evaluated in terms of face, content, construct and criterion validity in addition to internal and test-retest reliability. A convenience sample of 285 working adults aged 20–50 living in Mashad was recruited (91% response rate) to evaluate the Persian version. RESULTS: The Persian version of OIDP had excellent validity and reliability charactersitics. Weighted Kappa was 0.91. Cronbachs alpha coefficient was 0.79. The index showed significant associations with self-rated oral and general health status, as well as perceived dental treatment needs, satisfaction with mouth and prevalence of pain in mouth (P < 0.001). 64.9% of subjects had an oral impact on their daily performances. The most prevalent performance affected was eating, followed by major work or role and sleeping. CONCLUSION: The Persian version of OIDP index is a valid and reliable measure for use in 20 to 50 year old working Iranians

Provenance of Cretaceous through Eocene strata of the Four Corners region: Insights from detrital zircons in the San Juan Basin, New Mexico and Colorado

Cretaceous through Eocene strata of the Four Corners region provide an excellent record of changes in sediment provenance from Sevier thin-skinned thrusting through the formation of Laramide block uplifts and intra-foreland basins. During the ca. 125–50 Ma timespan, the San Juan Basin was flanked by the Sevier thrust belt to the west, the Mogollon highlands rift shoulder to the southwest, and was influenced by (ca. 75–50 Ma) Laramide tectonism, ultimately preserving a >6000 ft (>2000 m) sequence of continental, marginal-marine, and offshore marine sediments. In order to decipher the influences of these tectonic features on sediment delivery to the area, we evaluated 3228 U-Pb laser analyses from 32 detrital-zircon samples from across the entire San Juan Basin, of which 1520 analyses from 16 samples are newly reported herein. The detrital-zircon results indicate four stratigraphic intervals with internally consistent age peaks: (1) Lower Cretaceous Burro Canyon Formation, (2) Turonian (93.9–89.8 Ma) Gallup Sandstone through Campanian (83.6–72.1 Ma) Lewis Shale, (3) Campanian Pictured Cliffs Sandstone through Campanian Fruitland Formation, and (4) Campanian Kirtland Sandstone through Lower Eocene (56.0–47.8 Ma) San Jose Formation. Statistical analysis of the detrital-zircon results, in conjunction with paleocurrent data, reveals three distinct changes in sediment provenance. The first transition, between the Burro Canyon Formation and the Gallup Sandstone, reflects a change from predominantly reworked sediment from the Sevier thrust front, including uplifted Paleozoic sediments and Mesozoic eolian sandstones, to a mixed signature indicating both Sevier and Mogollon derivation. Deposition of the Pictured Cliffs Sandstone at ca. 75 Ma marks the beginning of the second transition and is indicated by the spate of near-depositional-age zircons, likely derived from the Laramide porphyry copper province of southern Arizona and southwestern New Mexico. Paleoflow indicators suggest the third change in provenance was complete by 65 Ma as recorded by the deposition of the Paleocene Ojo Alamo Sandstone. However, our new U-Pb detrital-zircon results indicate this transition initiated ∼8 m.y. earlier during deposition of the Campanian Kirtland Formation beginning ca. 73 Ma. This final change in provenance is interpreted to reflect the unroofing of surrounding Laramide basement blocks and a switch to local derivation. At this time, sediment entering the San Juan Basin was largely being generated from the nearby San Juan Mountains to the north-northwest, including uplift associated with early phases of Colorado mineral belt magmatism. Thus, the detrital-zircon spectra in the San Juan Basin document the transition from initial reworking of the Paleozoic and Mesozoic cratonal blanket to unroofing of distant basement-cored uplifts and Laramide plutonic rocks, then to more local Laramide uplifts.National Science Foundation (NSF grant EAR-1649254

HMOX1 Gene Promoter Alleles and High HO-1 Levels Are Associated with Severe Malaria in Gambian Children

Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)n repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)n repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]