Association between urinary sodium, creatinine, albumin, and long term survival in chronic kidney disease

Dietary sodium intake is associated with hypertension and cardiovascular risk in the general population. In patients with chronic kidney disease, sodium intake has been associated with progressive renal disease, but not independently of proteinuria. We studied the relationship between urinary sodium excretion and urinary sodium:creatinine ratio and mortality or requirement for renal replacement therapy in chronic kidney disease. Adults attending a renal clinic who had at least one 24-hour urinary sodium measurement were identified. 24-hour urinary sodium measures were collected and urinary sodium:creatinine ratio calculated. Time to renal replacement therapy or death was recorded. 423 patients were identified with mean estimated glomerular filtration rate of 48ml/min/1.73m<sup>2</sup>. 90 patients required renal replacement therapy and 102 patients died. Mean slope decline in estimated glomerular filtration rate was -2.8ml/min/1.73m<sup>2</sup>/year. Median follow-up was 8.5 years. Patients who died or required renal replacement therapy had significantly higher urinary sodium excretion and urinary sodium:creatinine but the association with these parameters and poor outcome was not independent of renal function, age and albuminuria. When stratified by albuminuria, urinary sodium:creatinine was a significant cumulative additional risk for mortality, even in patients with low level albuminuria. There was no association between low urinary sodium and risk, as observed in some studies. This study demonstrates an association between urinary sodium excretion and mortality in chronic kidney disease, with a cumulative relationship between sodium excretion, albuminuria and reduced survival. These data support reducing dietary sodium intake in chronic kidney disease but further study is required to determine the target sodium intake

Cell-free translation and purification of Arabidopsis thaliana regulator of G signaling 1 protein

Arabidopsis thaliana Regulator of G protein Signalling 1 (AtRGS1) is a protein with a predicted N-terminal 7-transmembrane (7TM) domain and a C-terminal cytosolic RGS1 box domain. The RGS1 box domain exerts GTPase activation (GAP) activity on Gα (AtGPA1), a component of heterotrimeric G protein signaling in plants. AtRGS1 may perceive an exogenous agonist to regulate the steady-state levels of the active form of AtGPA1. It is uncertain if the full length RGS1 protein exerts any atypical effects on Gα, nor has it been established exactly how AtRGS1 contributes to perception of an extracellular signal and transmits this response to a G-protein dependent signaling cascade. Such an understanding can be deduced from in vitro studies using the purified and soluble RGS1-box domain. Further studies on full-length AtRGS1 have been inhibited due to the extreme low abundance of the endogenous AtRGS1 protein in plants and lack of a suitable heterologous system to express AtRGS1. Here, we describe methods to produce full-length AtRGS1 by cell free synthesis into unilamellar liposomes and nanodiscs. The cell-free synthesized AtRGS1 exhibits GTPase activating activity on Gα and can be purified to a level suitable for biochemical analyses

A taste of the deep-sea: The roles of gustatory and tactile searching behaviour in the grenadier fish <i>Coryphaenoides armatus</i>

The deep-sea grenadier fishes (Coryphaenoides spp.) are among the dominant predators and scavengers in the ocean basins that cover much of Earth's surface. Baited camera experiments were used to study the behaviour of these fishes. Despite the apparent advantages of rapidly consuming food, grenadiers attracted to bait spend a large proportion of their time in prolonged periods of non-feeding activity. Video analysis revealed that fish often adopted a head-down swimming attitude (mean of 21.3 degrees between the fish and seafloor), with swimming velocity negatively related to attitude. The fish also swam around and along vertical and horizontal structures of the lander with their head immediately adjacent to the structure. We initially hypothesised that this behaviour was associated with the use of the short chin barbel in foraging. Barbel histology showed numerous taste buds in the skin, and a barbel nerve with about 20,000 axons in adult fish. A tracing experiment in one undamaged animal revealed the termination fields of the barbel neurons in the trigeminal and rhombencephalic regions, indicating both a mechanoreceptory and a gustatory role for the barbel. Our conclusion was that olfactory foraging becomes ineffective at close ranges and is followed by a search phase using tactile and gustatory sensing by the barbel. The development of this sensory method probably co-evolved alongside behavioural changes in swimming mechanics to allow postural stability at low swimming speeds

B \to K(K^*) missing energy in Unparticle physics

In the present work we study the effects of an unparticle \unpart as the possible source of missing energy in the decay $B \to K (K^*) + {\rm missing energy}$. We find that the dependence of the differential branching ratio on the $K$($K^*$)-meson's energy in the presence of the vector unparticle operators is very distinctive from that of the SM. Moreover, in using the existing upper bound on $B \to K (K^*) + {\rm missing energy}$ decays, we have been able to put more stringent constraints on the parameters of unparticle stuff.Comment: 13 pages, 5 figure

Effect of PSI-697, a novel P-selectin inhibitor, on platelet-monocyte aggregate formation in humans

Background: Platelet activation is central to the pathogenesis of acute coronary syndromes. Surface expression of P‐selectin on activated platelets induces formation of platelet–monocyte aggregates and promotes vascular inflammation and thrombosis. P‐selectin antagonism may represent a novel therapeutic strategy in vascular disease. We aimed to investigate the effects of the novel P‐selectin antagonist PSI‐697 on platelet–monocyte aggregate formation in humans. Methods and Results: In a double‐blind, randomized, placebo‐controlled crossover study, healthy smokers were randomized to receive either oral PSI‐697 600 mg or matched placebo. The sequence of treatment was also randomized, with all subjects receiving both PSI‐697 and placebo. Platelet–monocyte aggregates were measured by flow cytometry at 4 and 24 hours in the presence and absence of thrombin receptor‐activating peptide (TRAP; 0.1 to 1.0 μm/L). The ex vivo addition of TRAP caused a concentration‐dependent increase in platelet–monocyte aggregates from 8.2% to 94.8% (P&lt;0.001). At 4 and 24 hours, plasma concentrations of PSI‐697 increased to 1906 and 83 ng/mL, respectively (P&lt;0.001). PSI‐697 had no demonstrable effect on either stimulated or unstimulated platelet–monocyte aggregates at 4 or 24 hours (P&gt;0.05). P‐selectin‐blocking antibody (CLB‐Thromb6), but not PSI‐697, inhibited both stimulated and unstimulated platelet–monocyte aggregate formation in vitro (P&lt;0.001). Conclusions: The novel small‐molecule P‐selectin antagonist PSI‐697 did not inhibit basal or stimulated platelet–monocyte aggregate formation in humans at the dose tested. Its clinical efficacy remains to be established

In-situ fluorescence spectroscopy indicates total bacterial abundance and dissolved organic carbon

We explore in-situ fluorescence spectroscopy as an instantaneous indicator of total bacterial abundance and faecal contamination in drinking water. Eighty-four samples were collected outside of the recharge season from groundwater-derived water sources in Dakar, Senegal. Samples were analysed for tryptophan-like (TLF) and humic-like (HLF) fluorescence in-situ, total bacterial cells by flow cytometry, and potential indicators of faecal contamination such as thermotolerant coliforms (TTCs), nitrate, and in a subset of 22 samples, dissolved organic carbon (DOC). Significant single-predictor linear regression models demonstrated that total bacterial cells were the most effective predictor of TLF, followed by on-site sanitation density; TTCs were not a significant predictor. An optimum multiple-predictor model of TLF incorporated total bacterial cells, nitrate, nitrite, on-site sanitation density, and sulphate (r2 0.68). HLF was similarly related to the same parameters as TLF, with total bacterial cells being the best correlated (ρs 0.64). In the subset of 22 sources, DOC clustered with TLF, HLF, and total bacterial cells, and a linear regression model demonstrated HLF was the best predictor of DOC (r2 0.84). The intergranular nature of the aquifer, timing of the study, and/or non-uniqueness of the signal to TTCs can explain the significant associations between TLF/HLF and indicators of faecal contamination such as on-site sanitation density and nutrients but not TTCs. The bacterial population that relates to TLF/HLF is likely to be a subsurface community that develops in-situ based on the availability of organic matter originating from faecal sources. In-situ fluorescence spectroscopy instantly indicates a drinking water source is impacted by faecal contamination but it remains unclear how that relates specifically to microbial risk in this setting

Constraints on Astro-unparticle Physics from SN 1987A

SN 1987A observations have been used to place constraints on the interactions between standard model particles and unparticles. In this study we calculate the energy loss from the supernovae core through scalar, pseudo scalar, vector, pseudo vector unparticle emission from nuclear bremsstrahlung for degenerate nuclear matter interacting through one pion exchange. In order to examine the constraints on $d_{\cal U}=1$ we considered the emission of scalar, pseudo scalar, vector, pseudo vector and tensor through the pair annihilation process $e^+e^-\to {\cal U} \gamma$. In addition we have re-examined other pair annihilation processes. The most stringent bounds on the dimensionless coupling constants for $d_{\cal U} =1$ and $\Lambda_{\cal U}= m_Z$ are obtained from nuclear bremsstrahlung process for the pseudo scalar and pseudo-vector couplings $\bigl|\lambda^{\cal P}_{0,1}\bigr|\leq 4\times 10^{-11}$ and for tensor interaction, the best limit on dimensionless coupling is obtained from $e^+ e^-\to {\cal U} \gamma$ and we get $\bigl|\lambda^{\cal T}\bigr| \leq 6\times 10^{-6}$.Comment: 12 pages, 2 postscript figure

The physical oceanography of the transport of floating marine debris

Marine plastic debris floating on the ocean surface is a major environmental problem. However, its distribution in the ocean is poorly mapped, and most of the plastic waste estimated to have entered the ocean from land is unaccounted for. Better understanding of how plastic debris is transported from coastal and marine sources is crucial to quantify and close the global inventory of marine plastics, which in turn represents critical information for mitigation or policy strategies. At the same time, plastic is a unique tracer that provides an opportunity to learn more about the physics and dynamics of our ocean across multiple scales, from the Ekman convergence in basin-scale gyres to individual waves in the surfzone. In this review, we comprehensively discuss what is known about the different processes that govern the transport of floating marine plastic debris in both the open ocean and the coastal zones, based on the published literature and referring to insights from neighbouring fields such as oil spill dispersion, marine safety recovery, plankton connectivity, and others. We discuss how measurements of marine plastics (both in situ and in the laboratory), remote sensing, and numerical simulations can elucidate these processes and their interactions across spatio-temporal scales

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Comparing ocean surface boundary vertical mixing schemes including langmuir turbulence

Six recent Langmuir turbulence parameterization schemes and five traditional schemes are implemented in a common single‐column modeling framework and consistently compared. These schemes are tested in scenarios versus matched large eddy simulations, across the globe with realistic forcing (JRA55‐do, WAVEWATCH‐III simulated waves) and initial conditions (Argo), and under realistic conditions as observed at ocean moorings. Traditional non‐Langmuir schemes systematically underpredict large eddy simulation vertical mixing under weak convective forcing, while Langmuir schemes vary in accuracy. Under global, realistic forcing Langmuir schemes produce 6% (−1% to 14% for 90% confidence) or 5.2 m (−0.2 m to 17.4 m for 90% confidence) deeper monthly mean mixed layer depths than their non‐Langmuir counterparts, with the greatest differences in extratropical regions, especially the Southern Ocean in austral summer. Discrepancies among Langmuir schemes are large (15% in mixed layer depth standard deviation over the mean): largest under wave‐driven turbulence with stabilizing buoyancy forcing, next largest under strongly wave‐driven conditions with weak buoyancy forcing, and agreeing during strong convective forcing. Non‐Langmuir schemes disagree with each other to a lesser extent, with a similar ordering. Langmuir discrepancies obscure a cross‐scheme estimate of the Langmuir effect magnitude under realistic forcing, highlighting limited understanding and numerical deficiencies. Maps of the regions and seasons where the greatest discrepancies occur are provided to guide further studies and observations