Guiding properties of a non-isothermal atmosphere for acoustic-gravity waves

The propagation of pressure waves in a stratified, non-isothermal atmosphere is studied in the linear approximation. It is found that acoustic and acoustic-gravity waves can be horizontally guided by the effect of the Earth’s thermocline alone, under very mild conditions on the temperature gradient steepness. The effect of the Earth’s surface is also studied. Lamb’s modes associated with the rigid surface are, then, identified and their behaviour, as a function of the Earth’s position, is discussed. Finally, dissipation is included, and its effect is derived using a perturbation technique

A homeostatic function of CXCR2 signalling in articular cartilage

Funding This work was funded by Arthritis Research UK (grants 17859, 17971, 19654), INNOCHEM EU FP6 (grant LSHB-CT-2005-51867), MRC (MR/K013076/1) and the William Harvey Research FoundationPeer reviewedPublisher PD

Intra-parenchymal renal resistive index variation (IRRIV) describes renal functional reserve (RFR): Pilot study in healthy volunteers

An increase of glomerular filtration rate after protein load represents renal functional reserve (RFR) and is due to afferent arteriolar vasodilation. Lack of RFR may be a risk factor for acute kidney injury (AKI), but is cumbersome to measure. We sought to develop a non-invasive, bedside method that would indirectly measure RFR. Mechanical abdominal pressure, through compression of renal vessels, decreases blood flow and activates the auto-regulatory mechanism which can be measured by a fall in renal resistive index (RRI). The study aims at elucidating the relationship between intra-parenchymal renal resistive index variation (IRRIV) during abdominal pressure and RFR. In healthy volunteers, pressure was applied by a weight on the abdomen (fluid-bag 10% of subject's body weight) while RFR was measured through a protein loading test. We recorded RRI in an interlobular artery after application of pressure using ultrasound. The maximum percentage reduction of RRI from baseline was compared in the same subject to RFR. We enrolled 14 male and 16 female subjects (mean age 38 ± 14 years). Mean creatinine clearance was 106.2 ± 16.4 ml/min/1.73 m2. RFR ranged between -1.9 and 59.7 with a mean value of 28.9 ± 13.1 ml/min/1.73 m2. Mean baseline RRI was 0.61 ± 0.05, compared to 0.49 ± 0.06 during abdominal pressure; IRRIV was 19.6 ± 6.7%, ranging between 3.1% and 29.2%. Pearson's coefficient between RFR and IRRIV was 74.16% (p < 0.001). Our data show the correlation between IRRIV and RFR. Our results can lead to the development of a "stress test" for a rapid screen of RFR to establish renal susceptibility to different exposures and the consequent risk for AKI

Generating a Wnt switch: it’s all about the right dosage

Wnt proteins can activate different branches of the Wnt signaling pathway, raising the question of specificity. In this issue, Nalesso et al. (2011. J. Cell Biol. doi:10.1083/jcb.201011051) provide an answer to this conundrum by showing that different concentrations of Wnt ligands can elicit different intracellular responses. These findings not only provide new insights into the molecular mechanisms underlying Wnt signaling, but also indicate how Wnt gradients might contribute to tissue patterning during embryogenesis

Determinazione di residui di sparo in ferite d\u2019arma da fuoco putrefatte mediante Micro-TC

Introduzione: La Micro-TC \ue8 un mezzo rapido e preciso per la determinazione del gunshot-residue (GSR) su ferite d\u2019arma da fuoco ai fini della determinazione della distanza di sparo. \uc8 noto come la disepitelizzazione e la colliquazione della cute e del sottocute indotte dai fenomeni autolitici-putrefattivi rendano difficoltosa l\u2019analisi ispettiva delle ferite cutanee. Il presente studio si propone di testare l\u2019efficienza diagnostica della Micro-TC nell\u2019identificazione e quantificazione del GSR su ferite d\u2019arma da fuoco sottoposte a putrefazione standardizzata. Materiali e metodi: Previa autorizzazione del Comitato Etico, 10 gambe umane amputate chirurgicamente sono state sezionate in 3 segmenti di circa 6 cm (totale 30 segmenti) e sottoposte a prove di sparo da tre differenti distanze (5, 15 e 30 cm) mediante l\u2019utilizzo di una pistola semi-automatica calibro 7.65 mm fissata su un supporto rigido. I pezzi anatomici sono stati posti in cassette di legno, conservati all\u2019aria aperta per 10 giorni e successivamente fissati in formalina al 4%. Sono stati quindi ottenuti campioni cutanei di forma cubica (lato di cm 1) comprendenti il foro di ingresso o di uscita, il tramite e i tessuti molli circostanti. Ogni campione \ue8 stato sottoposto a esame con Micro-TC e ricostruito in 3D. La percentuale di GSR nella regione di interesse \ue8 stata calcolata mediante un software densitometrico analizzando solo particelle con densit\ue0 superiore a 1000 HU. La stima statistica del modello sulla base del campione rilevato \ue8 stata effettuata mediante la procedura PROC NLIN di SAS\uae. Risultati: L\u2019analisi ispettiva delle ferite immediatamente dopo le prove balistiche ha evidenziato una progressiva riduzione dell\u2019alone di affumicatura e del tatuaggio all\u2019aumentare della distanza di sparo. A distanza di 10 giorni le caratteristiche accessorie apparivano pi\uf9 sfumate a causa delle modificazioni post-mortali della cute associate alla presenza di larve e muffe. L\u2019analisi con micro-CT ha consentito di individuare residui di sparo sulla superficie cutanea, nel sottocute e lungo il tramite di tutte le ferite di ingresso. Tali residui erano invece sempre assenti a livello dei fori d\u2019uscita. La percentuale di GSR ha mostrato un decremento non lineare al crescere della distanza di sparo; nonostante ci\uf2, la variabilit\ue0 del fenomeno non ha permesso di evidenziare differenze statisticamente significative nella media e deviazione standard dei valori relativi alle diverse distanze testate. Conclusioni: L\u2019analisi con micro-TC di ferite d\u2019arma da fuoco prodotte da colpi esplosi a distanza medio-bassa (fino a 30 cm) consente di porre diagnosi differenziale tra foro di ingresso e di uscita. Le modificazioni cutanee indotte dai fenomeni autolitici e putrefattivi post-mortali inducono una tale variabilit\ue0 nei risultati tale da non permettere l\u2019utilizzo di tale tecnica nella determinazione della distanza di sparo

Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review

INTRODUCTION: Severe sepsis and septic shock are common problems in the intensive care unit and carry a high mortality. Endotoxin, one of the principal components on the outer membrane of gram-negative bacteria, is considered important to their pathogenesis. Polymyxin B bound and immobilized to polystyrene fibers (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption, theoretically preventing the progression of the biological cascade of sepsis. We performed a systematic review to describe the effect in septic patients of direct hemoperfusion with PMX-F on outcomes of blood pressure, use of vasoactive drugs, oxygenation, and mortality reported in published studies. METHODS: We searched PubMed, the Cochrane Collaboration Database, and bibliographies of retrieved articles and consulted with experts to identify relevant studies. Prospective and retrospective observational studies, pre- and post-intervention design, and randomized controlled trials were included. Three authors reviewed all citations. We identified a total of 28 publications - 9 randomized controlled trials, 7 non-randomized parallel studies, and 12 pre-post design studies - that reported at least one of the specified outcome measures (pooled sample size, 1,425 patients: 978 PMX-F and 447 conventional medical therapy). RESULTS: Overall, mean arterial pressure (MAP) increased by 19 mm Hg (95% confidence interval [CI], 15 to 22 mm Hg; p < 0.001), representing a 26% mean increase in MAP (range, 14% to 42%), whereas dopamine/dobutamine dose decreased by 1.8 microg/kg per minute (95% CI, 0.4 to 3.3 microg/kg per minute; p = 0.01) after PMX-F. There was significant intertrial heterogeneity for these outcomes (p < 0.001), which became non-significant when analysis was stratified for baseline MAP. The mean arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio increased by 32 units (95% CI, 23 to 41 units; p < 0.001). PMX-F therapy was associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI, 0.43 to 0.65). The trials assessed had suboptimal method quality. CONCLUSION: Based on this critical review of the published literature, direct hemoperfusion with PMX-F appears to have favorable effects on MAP, dopamine use, PaO2/FiO2 ratio, and mortality. However, publication bias and lack of blinding need to be considered. These findings support the need for further rigorous study of this therapy

Movements of scalloped hammerhead sharks (Sphyrna lewini) at Cocos Island, Costa Rica and between oceanic islands in the Eastern Tropical Pacific

Many species of sharks form aggregations around oceanic islands, yet their levels of residency and their site specificity around these islands may vary. In some cases, the waters around oceanic islands have been designated as marine protected areas, yet the conservation value for threatened shark species will depend greatly on how much time they spend within these protected waters. Eighty-four scalloped hammerhead sharks (Sphyrna lewini Griffith & Smith), were tagged with acoustic transmitters at Cocos Island between 2005–2013. The average residence index, expressed as a proportion of days present in our receiver array at the island over the entire monitoring period, was 0.52±0.31, implying that overall the sharks are strongly associated with the island. Residency was significantly greater at Alcyone, a shallow seamount located 3.6 km offshore from the main island, than at the other sites. Timing of presence at the receiver locations was mostly during daytime hours. Although only a single individual from Cocos was detected on a region-wide array, nine hammerheads tagged at Galapagos and Malpelo travelled to Cocos. The hammerheads tagged at Cocos were more resident than those visiting from elsewhere, suggesting that the Galapagos and Malpelo populations may use Cocos as a navigational waypoint or stopover during seasonal migrations to the coastal Central and South America. Our study demonstrates the importance of oceanic islands for this species, and shows that they may form a network of hotspots in the Eastern Tropical Pacific

Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis

WNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. We identified Heme Oxygenase I (HMOX1) and Sox-9 as specific markers of the WNT/CaMKII signalling in articular chondrocytes through a microarray analysis. We showed that the expression of the activated form of CaMKII, phospho-CaMKII, was increased in human and murine osteoarthritis and the expression of HMOX1 was accordingly reduced, demonstrating the activation of the pathway during disease progression. To elucidate its function, we administered the CaMKII inhibitor KN93 to mice in which osteoarthritis was induced by resection of the anterior horn of the medial meniscus and of the medial collateral ligament in the knee joint. Pharmacological blockade of CaMKII exacerbated cartilage damage and bone remodelling. Finally, we showed that CaMKII inhibition in articular chondrocytes upregulated the expression of matrix remodelling enzymes alone and in combination with Interleukin 1. These results suggest an important homeostatic role of the WNT/CaMKII signalling in osteoarthritis which could be exploited in the future for therapeutic purposes

The App-Runx1 Region Is Critical for Birth Defects and Electrocardiographic Dysfunctions Observed in a Down Syndrome Mouse Model

Down syndrome (DS) leads to complex phenotypes and is the main genetic cause of birth defects and heart diseases. The Ts65Dn DS mouse model is trisomic for the distal part of mouse chromosome 16 and displays similar features with post-natal lethality and cardiovascular defects. In order to better understand these defects, we defined electrocardiogram (ECG) with a precordial set-up, and we found conduction defects and modifications in wave shape, amplitudes, and durations in Ts65Dn mice. By using a genetic approach consisting of crossing Ts65Dn mice with Ms5Yah mice monosomic for the App-Runx1 genetic interval, we showed that the Ts65Dn viability and ECG were improved by this reduction of gene copy number. Whole-genome expression studies confirmed gene dosage effect in Ts65Dn, Ms5Yah, and Ts65Dn/Ms5Yah hearts and showed an overall perturbation of pathways connected to post-natal lethality (Coq7, Dyrk1a, F5, Gabpa, Hmgn1, Pde10a, Morc3, Slc5a3, and Vwf) and heart function (Tfb1m, Adam19, Slc8a1/Ncx1, and Rcan1). In addition cardiac connexins (Cx40, Cx43) and sodium channel sub-units (Scn5a, Scn1b, Scn10a) were found down-regulated in Ts65Dn atria with additional down-regulation of Cx40 in Ts65Dn ventricles and were likely contributing to conduction defects. All these data pinpoint new cardiac phenotypes in the Ts65Dn, mimicking aspects of human DS features and pathways altered in the mouse model. In addition they highlight the role of the App-Runx1 interval, including Sod1 and Tiam1, in the induction of post-natal lethality and of the cardiac conduction defects in Ts65Dn. These results might lead to new therapeutic strategies to improve the care of DS people