Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura

Background Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS. Methods We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA. Results The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605–28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693–21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064–0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029–0.813; P=0.017). Conclusion These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients

Geomagnetic Semiannual Variation Is Not Overestimated and Is Not an Artifact of Systematic Solar Hemispheric Asymmetry

Mursula et al. [2011] (MTL11) suggest that there is a 22-year variation in solar wind activity that coupled with the variation in heliographic latitude of the Earth during the year, gives rise to an apparent semiannual variation of geomagnetic activity in averages obtained over several solar cycles. They conclude that the observed semiannual variation is seriously overestimated and is largely an artifact of this inferred 22-year variation. We show: (1) that there is no systematically alternating annual variation of geomagnetic activity or of the solar driver, changing with the polarity of the solar polar fields, (2) that the universal time variation of geomagnetic activity at all times have the characteristic imprint of the equinoctial hypothesis rather than that of the axial hypothesis required by the suggestion of MTL11, and (3) that the semiannual variation is not an artifact, is not overestimated, and does not need revision.Comment: Submitted to GR

Is resistance to ischaemia of motor axons in diabetic subjects due to membrane depolarization?

The reasons for the resistance to ischaemia of peripheral nerves in diabetics are not well understood. We have now explored whether axonal depolarization underlies this phenomenon, as has previously been proposed. Resistance to ischaemia was determined by the new method of “threshold tracking”. This method revealed an increase in excitability of the peroneal nerve at the popliteal fossa during ischaemia, and a decrease in excitability in the post-ischaemic period. The extent of these alterations in 28 type 1 diabetics without peripheral neuropathy showed a strong correlation with the mean blood glucose concentrations during the last 24 h before examination. To test whether the ischaemic resistance was related to membrane potential, we also measured axonal superexcitability in 11 selected diabetics, since it has been shown that post-spike changes in excitability depend on membrane potential. Changes in excitability of the peroneal nerve were measured in the period between 10 and 30 msec following a conditioning supramaximal compound action potential. Under resting conditions, no differences in the post-spike superexcitability were found between controls and diabetics, despite striking differences in their responses to a 10-min pressure cuff. These observations indicate that membrane depolarization is not involved in the resistance to ischaemia of motor axons in diabetic subjects

Reversible Dysphasia and Statins

This paper presents a case of reversible dysphasia occurring in a patient prescribed atorvastatin in combination with indapamide. A milder dysphasia recurred with the prescription of rosuvastatin and was documented on clinical examination. This resolved following cessation of rosuvastatin. The case highlights both a need for a wider understanding of potential drug interactions through the CYP 450 system and for an increased awareness, questioning and reporting of drug side-effects

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

X Chromosome Sites Autonomously Recruit the Dosage Compensation Complex in Drosophila Males

It has been proposed that dosage compensation in Drosophila males occurs by binding of two core proteins, MSL-1 and MSL-2, to a set of 35–40 X chromosome “entry sites” that serve to nucleate mature complexes, termed compensasomes, which then spread to neighboring sequences to double expression of most X-linked genes. Here we show that any piece of the X chromosome with which compensasomes are associated in wild-type displays a normal pattern of compensasome binding when inserted into an autosome, independently of the presence of an entry site. Furthermore, in chromosomal rearrangements in which a piece of X chromosome is inserted into an autosome, or a piece of autosome is translocated to the X chromosome, we do not observe spreading of compensasomes to regions of autosomes that have been juxtaposed to X chromosomal material. Taken together these results suggest that spreading is not involved in dosage compensation and that nothing distinguishes an entry site from the other X chromosome sites occupied by compensasomes beyond their relative affinities for compensasomes. We propose a new model in which the distribution of compensasomes along the X chromosome is achieved according to the hierarchical affinities of individual binding sites

A Cross National Study of Golf Tourists’ Satisfaction

The purpose of this study was two-fold: firstly, it was to examine the determinants satisfaction levels of golf tourists and secondly to investigate if these vary across golf tourists’ country of residence. Using data collected through a survey of golf tourists visiting Lisbon (Portugal), attributes directly related to playing golf as well as more generic destination attributes were examined as potential determinants of golf tourists’ satisfaction. The data was analysed in two stages by the means of logistic regression. In stage one, the analysis was based on a representative sample of golf tourists to the region. In the second stage, two separate analyses were undertaken, one examining the satisfaction of Nordic golf tourists and another of British golf tourists (the two main markets for Lisbon). The results indicate that the satisfaction level of golf tourists is influenced by several factors, including those related to perceived quality and value. In addition, the results suggest that satisfaction is influenced by cross-cultural differences. While some determinants were important influences for both the British and the Nordic golfers, other determinants were specific to each country of origin. lytoinvestigateifthesevaryacrossgolftourists’countryofresidence.Using data collectedthroughasurveyofgolftouristsvisitingLisbon(Portugal),attributesdirectlyrelatedto playinggolfaswellasmoregenericdestinationattributeswereexaminedaspotentialdeterminantsof golf tourists’satisfaction.Thedatawasanalysedintwostagesbythemeansoflogisticregression.In stage one,theanalysiswasbasedonarepresentativesampleofgolftouriststotheregion.Inthesecond stage, twoseparateanalyseswereundertaken,oneexaminingthesatisfactionofNordicgolftourists and anotherofBritishgolftourists(thetwomainmarketsforLisbon).Theresultsindicatethatthe satisfactionlevelofgolftouristsisinfluencedbyseveralfactors,includingthoserelatedtoperceived qualityandvalue.Inaddition,theresultssuggestthatsatisfactionisinfluencedbycross-cultural differences.WhilesomedeterminantswereimportantinfluencesforboththeBritishandtheNordic golfers,otherdeterminantswerespecifictoeachcountryoforigin

Supermassive black hole ancestors

We study a model in which supermassive black holes (SMBHs) can grow by the combined action of gas accretion on heavy seeds and mergers of both heavy (m_s^h=10^5 Msol) and light (m_s^l = 10^2 Msol) seeds. The former result from the direct collapse of gas in T_s^h >1.5x10^4K, H_2-free halos; the latter are the endproduct of a standard H_2-based star formation process. The H_2-free condition is attained by exposing halos to a strong (J_21 > 10^3) Lyman-Werner UV background produced by both accreting BHs and stars, thus establishing a self-regulated growth regime. We find that this condition is met already at z close to 18 in the highly biased regions in which quasars are born. The key parameter allowing the formation of SMBHs by z=6-7 is the fraction of halos that can form heavy seeds: the minimum requirement is that f_heavy>0.001; SMBH as large as 2x10^10 Msol can be obtained when f_heavy approaches unity. Independently of f_heavy, the model produces a high-z stellar bulge-black hole mass relation which is steeper than the local one, implying that SMBHs formed before their bulge was in place. The formation of heavy seeds, allowed by the Lyman-Werner radiative feedback in the quasar-forming environment, is crucial to achieve a fast growth of the SMBH by merger events in the early phases of its evolution, i.e. z>7. The UV photon production is largely dominated by stars in galaxies, i.e. black hole accretion radiation is sub-dominant. Interestingly, we find that the final mass of light BHs and of the SMBH in the quasar is roughly equal by z=6; by the same time only 19% of the initial baryon content has been converted into stars. The SMBH growth is dominated at all epochs z > 7.2 by mergers (exceeding accretion by a factor 2-50); at later times accretion becomes by far the most important growth channel. We finally discuss possible shortcomings of the model.Comment: 12 pages, 9 figures, 1 table, MNRAS in pres

Engaging consumer through the storefront: evidences from integrating interactive technologies

Although previous studies identified the importance of storefront windows on consumer’s entry decision, there is still a lack of research on engaging consumers at the storefront through the integration with interactive technologies. The purpose of this study is to carry out an exploratory investigation into the consumers preference for a certain store based on the storefront windows (in terms of entry decision), with emphasis on the current most attractive interactive technologies. Thus, we examine the extent to which an exploratory sample of consumers is influenced by storefront interactive technologies. Emotional aspects emerge as the most influencing ones in the case of traditional storefronts, while both emotional and functional aspects emerge as the most influencing factors while considering the integration of interactive technologies. In particular, our results shed light on the way these elements can be managed for the design of future attractive storefront windows, by providing important insights for scholars and practitioners

Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post- transplant serum creatinine when compared to “Gold Standard” clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future