Three-dimensional flow in Kupffer's Vesicle.

Whilst many vertebrates appear externally left-right symmetric, the arrangement of internal organs is asymmetric. In zebrafish, the breaking of left-right symmetry is organised by Kupffer's Vesicle (KV): an approximately spherical, fluid-filled structure that begins to form in the embryo 10 hours post fertilisation. A crucial component of zebrafish symmetry breaking is the establishment of a cilia-driven fluid flow within KV. However, it is still unclear (a) how dorsal, ventral and equatorial cilia contribute to the global vortical flow, and (b) if this flow breaks left-right symmetry through mechanical transduction or morphogen transport. Fully answering these questions requires knowledge of the three-dimensional flow patterns within KV, which have not been quantified in previous work. In this study, we calculate and analyse the three-dimensional flow in KV. We consider flow from both individual and groups of cilia, and (a) find anticlockwise flow can arise purely from excess of cilia on the dorsal roof over the ventral floor, showing how this vortical flow is stabilised by dorsal tilt of equatorial cilia, and (b) show that anterior clustering of dorsal cilia leads to around 40 % faster flow in the anterior over the posterior corner. We argue that these flow features are supportive of symmetry breaking through mechano-sensory cilia, and suggest a novel experiment to test this hypothesis. From our new understanding of the flow, we propose a further experiment to reverse the flow within KV to potentially induce situs inversus.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00285-016-0967-

Primary Superficial Vein Reflux with Competent Saphenous Trunk

AbstractObjectives: because reflux in superficial vein tributaries is most often collectively reported with the main saphenous veins, its importance remains largely unrecognised. This study was designed to identify the distribution and extent of non-truncal superficial venous reflux and its association with the signs and symptoms of chronic venous disease (CVD). Patients and methods: eighty-four limbs in 62 patients with signs and symptoms of CVD and evidence of reflux on continuous-wave Doppler were subsequently examined with colour-flow duplex imaging. Incompetent superficial vein tributaries were imaged throughout their extent and both ends were identified. Limbs with reflux in the main trunk of the saphenous veins or the deep, perforator or muscular veins, superficial or deep vein thrombosis, injection sclerotherapy, varicose-vein surgery, arterial disease and inflammation of non-venous origin were excluded from the study. The CEAP classification system was used for staging clinical severity of CVD. Results: the prevalence of tributary reflux alone was 9.7% (84/860). Reflux was detected in 171 tributaries. The number of incompetent tributaries ranged from 1 to 5 per limb. Most prevalent were the tributaries to the greater saphenous (111, 65%<0.0001), followed by those of lesser saphenous (33, 19%) or a combination of both (12, 7%). Incompetent non-saphenous tributaries were uncommon (15, 9%). Among the named tributaries in the lower limb the posterior arch vein was most often incompetent (46, 27%) followed by the anterolateral vein of the thigh (30, 18%), the medial accessory vein (16, 9%) and the anterior arch vein (14, 8%). Reflux in above-the-knee tributaries alone was found in 18 limbs (21%), in below the knee in 23 (28%) and in both sites in 43 (51%). The vast majority of the limbs (71%,p <0.0001) belonged to CVD class 2, 14% in class 3, 9% in class 1 and only 6% in class 4. Class 3 and 4 patients tended to have a longer duration of signs and symptoms, higher number of incompetent tributaries per limb and also a higher prevalence of combined above- and below-knee reflux. Conclusions: these data indicate that reflux confined to superficial tributaries is found throughout the lower limb. Because this reflux is present without greater and lesser saphenous trunk, perforator and deep-vein incompetence or proximal obstruction, it shows that reflux can develop in any vein without an apparent feeding source. Greater saphenous tributaries are affected significantly more often than those of lesser saphenous, while non-saphenous reflux is uncommon. Most limbs have signs and symptoms of CVD class 2 and 15% belong in classes 3 and 4

Independent predictors of failure up to 7.5 years after 35 386 single-brand cementless total hip replacements: a retrospective cohort study using National Joint Registry data

The popularity of cementless total hip replacement (THR) has surpassed cemented THR in England and Wales. This retrospective cohort study records survival time to revision following primary cementless THR with the most common combination (accounting for almost a third of all cementless THRs), and explores risk factors independently associated with failure, using data from the National Joint Registry for England and Wales. Patients with osteoarthritis who had a DePuy Corail/Pinnacle THR implanted between the establishment of the registry in 2003 and 31 December 2010 were included within analyses. There were 35 386 procedures. Cox proportional hazard models were used to analyse the extent to which the risk of revision was related to patient, surgeon and implant covariates. The overall rate of revision at five years was 2.4% (99% confidence interval 2.02 to 2.79). In the final adjusted model, we found that the risk of revision was significantly higher in patients receiving metal-on-metal (MoM: hazard ratio (HR) 1.93, p < 0.001) and ceramic-on-ceramic bearings (CoC: HR 1.55, p = 0.003) compared with the best performing bearing (metal-on-polyethylene). The risk of revision was also greater for smaller femoral stems (sizes 8 to 10: HR 1.82, p < 0.001) compared with mid-range sizes. In a secondary analysis of only patients where body mass index (BMI) data were available (n = 17 166), BMI ≥ 30 kg/m2 significantly increased the risk of revision (HR 1.55, p = 0.002). The influence of the bearing on the risk of revision remained significant (MoM: HR 2.19, p < 0.001; CoC: HR 2.09, p = 0.001). The risk of revision was independent of age, gender, head size and offset, shell, liner and stem type, and surgeon characteristics. We found significant differences in failure between bearing surfaces and femoral stem size after adjustment for a range of covariates in a large cohort of single-brand cementless THRs. In this study of procedures performed since 2003, hard bearings had significantly higher rates of revision, but we found no evidence that head size had an effect. Patient characteristics, such as BMI and American Society of Anesthesiologists grade, also influence the survival of cementless components

Inert gas clearance from tissue by co-currently and counter-currently arranged microvessels

To elucidate the clearance of dissolved inert gas from tissues, we have developed numerical models of gas transport in a cylindrical block of tissue supplied by one or two capillaries. With two capillaries, attention is given to the effects of co-current and counter-current flow on tissue gas clearance. Clearance by counter-current flow is compared with clearance by a single capillary or by two co-currently arranged capillaries. Effects of the blood velocity, solubility, and diffusivity of the gas in the tissue are investigated using parameters with physiological values. It is found that under the conditions investigated, almost identical clearances are achieved by a single capillary as by a co-current pair when the total flow per tissue volume in each unit is the same (i.e., flow velocity in the single capillary is twice that in each co-current vessel). For both co-current and counter-current arrangements, approximate linear relations exist between the tissue gas clearance rate and tissue blood perfusion rate. However, the counter-current arrangement of capillaries results in less-efficient clearance of the inert gas from tissues. Furthermore, this difference in efficiency increases at higher blood flow rates. At a given blood flow, the simple conduction-capacitance model, which has been used to estimate tissue blood perfusion rate from inert gas clearance, underestimates gas clearance rates predicted by the numerical models for single vessel or for two vessels with co-current flow. This difference is accounted for in discussion, which also considers the choice of parameters and possible effects of microvascular architecture on the interpretation of tissue inert gas clearance

A Full Pharmacological Analysis of the Three Turkey β-Adrenoceptors and Comparison with the Human β-Adrenoceptors

There are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations.Stable cell lines were constructed with each of the turkey β-adrenoceptors and 3H-CGP12177 whole cell binding, CRE-SPAP production and (3)H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4C-adrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation.There are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation

Quality science from quality measurement: The role of measurement type with respect to replication and effect size magnitude in psychological research

Copyright: © 2018 Kornbrot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The quality of psychological studies is currently a major concern. The Many Labs Project (MLP) and the Open-Science-Collaboration (OSC) have collected key data on replicability and statistical effect sizes. We build on this work by investigating the role played by three measurement types: ratings, proportions and unbounded (measures without conceptual upper limits, e.g. time). Both replicability and effect sizes are dependent on the amount of variability due to extraneous factors. We predicted that the role of such extraneous factors might depend on measurement type, and would be greatest for ratings, intermediate for proportions and least for unbounded. Our results support this conjecture. OSC replication rates for unbounded, 43% and proportion 40% combined are reliably higher than those for ratings at 20% (effect size, w = .20). MLP replication rates for the original studies are: pro- portion = .74, ratings = .40 (effect size w = .33). Original effect sizes (Cohen’s d) are highest for: unbounded OSC cognitive = 1.45, OSC social = .90); next for proportions (OSC cogni- tive = 1.01, OSC social = .84, MLP = .82); and lowest for ratings (OSC social = .64, MLP = .31). These findings are of key importance to scientific methodology and design, even if the reasons for their occurrence are still at the level of conjecture.Peer reviewe

Spin pumping in magnetic trilayer structures with an MgO barrier

We present a study of the interaction mechanisms in magnetic trilayer structures with an MgO barrier grown by molecular beam epitaxy. The interlayer exchange coupling, A ex, is determined using SQUID magnetometry and ferromagnetic resonance (FMR), displaying an unexpected oscillatory behaviour as the thickness, t MgO, is increased from 1 to 4 nm. Transmission electron microscopy confirms the continuity and quality of the tunnelling barrier, eliminating the prospect of exchange arising from direct contact between the two ferromagnetic layers. The Gilbert damping is found to be almost independent of the MgO thickness, suggesting the suppression of spin pumping. The element-specific technique of X-ray detected FMR reveals a small dynamic exchange interaction, acting in concert with the static interaction to induce coupled precession across the multilayer stack. These results highlight the potential of spin pumping and spin transfer torque for device applications in magnetic tunnel junctions relying on commonly used MgO barriers

Properties of an acid-tolerant, persistent Cheddar cheese isolate, Lacticaseibacillus paracasei GCRL163

The distinctive flavours in hard cheeses are attributed largely to the activity of nonstarter lactic acid bacteria (NSLAB) which dominate the cheese matrix during maturation after lactose is consumed. Understanding how different strains of NSLAB survive, compete, and scavenge available nutrients is fundamental to selecting strains as potential adjunct starters which may influence product traits. Three Lacticaseibacillus paracasei isolates which dominated at different stages over 63-week maturation periods of Australian Cheddar cheeses had the same molecular biotype. They shared many phenotypic traits, including salt tolerance, optimum growth temperature, growth on N-acetylglucosamine and N-acetylgalactosamine plus delayed growth on D-ribose, carbon sources likely present in cheese due to bacterial autolysis. However, strains 124 and 163 (later named GCRL163) survived longer at low pH and grew on D-tagatose and D-mannitol, differentiating this phenotype from strain 122. When cultured on growth-limiting lactose (0.2%, wt/vol) in the presence of high concentrations of L-leucine and other amino acids, GCRL163 produced, and subsequently consumed lactate, forming acetic and formic acids, and demonstrated temporal accumulation of intermediates in pyruvate metabolism in long-term cultures. Strain GCRL163 grew in Tween 80-tryptone broths, a trait not shared by all L. casei-group dairy isolates screened in this study. Including citrate in this medium stimulated growth of GCRL163 above citrate alone, suggesting cometabolism of citrate and Tween 80. Proteomic analysis of cytosolic proteins indicated that growth in Tween 80 produced a higher stress state and increased relative abundance of three cell envelope proteinases (CEPs) (including PrtP and Dumpy), amongst over 230 differentially expressed proteins