Maintenance of polar stratospheric clouds in a moist stratosphere

Previous work has shown that polar stratospheric clouds (PSCs) could have acted to substantially warm high latitude regions during past warm climates such as the Eocene (55 Ma). Using a simple model of stratospheric water vapor transport and polar stratospheric cloud (PSC) formation, we investigate the dependence of PSC optical depth on tropopause temperature, cloud microphysical parameters, stratospheric overturning, and tropospheric methane. We show that PSC radiative effects can help slow removal of water from the stratosphere via self-heating. However, we also show that the ability of PSCs to have a substantial impact on climate depends strongly on the PSC particle number density and the strength of the overturning circulation. Thus even a large source of stratospheric water vapor (e.g. from methane oxidation) will not result in substantial PSC radiative effects unless PSC ice crystal number density is high compared to most current observations, and stratospheric overturning (which modulates polar stratospheric temperatures) is low. These results are supported by analysis of a series of runs of the NCAR WACCM model with methane concentrations varying up to one thousand times present levels

Dual nature of Leydig cells of the human testis

This review is devoted to the human Leydig cell, and systematizes published and own unpublished results from studies performed during the last decade. Leydig cells are the main cell type in the testis that produce androgens which are important for the development of the male genital organs, secondary sex characteristics and behavior as well as for the processing and maintenance of spermatogenesis. A lot of information accumulated provides evidence that Leydig cells of the human testis and the testis of some other species express or possess immunoreactivities for numerous marker substances characteristic for nerve and neuroendocrine cells. It is shown that human Leydig cells, beside of markers for steroidogenic activity, possess: neuronal markers, synaptic and storage vesicle proteins, neural cytoskeletal proteins, 5-hydroxytryptamine, enzymes involved in the synthesis of catecholamines, neurohormones and/or their receptors, neuropeptides, calcium-binding proteins, cell adhesion molecules, glial cell antigens, components of the nitric oxide/cyclic guanosine monophosphate system, components of the renin/angiotensin system, and numerous growth factors and their receptors. These results provide new evidence for the neuroendocrine nature of Leydig cells. As consequence, two main questions arise: (i) the origin of Leydig cells and (ii) their functional significance as neuroendocrine cells. The presumption that Leydig cells originate from mesenchymal-like cells of the mesonephros is the most common view in the literature. However, no data are provided concerning the origin of the stem cells from which the Leydig cell lineage develops. Mesenchyme comprises the embryonic connective tissue cells that may have mesodermal, ectodermal and neuroectodermal (neural crest) origin. In this relation and based on the recently established neuroendocrine feature, we speculate that Leydig stem cells may detach from unknown regions of the neural crest and migrate to the mesonephric and gonadal anlage at early stages of development. The functional significance of Leydig cells as neuroendocrine cells is also illustrated on the basis of the nitric oxide/cyclic guanosine monophosphate system. Accordingly, Leydig cells may regulate their steroidogenic activity by an intracrine or autocrine fashion. Furthermore, they are probably able to synchronize the activity of the cells in a Leydig cell cluster by a paracrine way. Leydig cells may influence the contractile activity of the smooth muscle cells of blood vessels, thus regulating the blood flow rate and the permeability for hormones and nutritive substances. Also, Leydig cells may regulate the contractile state of peritubular myofibroblasts and myofibroblasts and smooth muscle cells of the tunica albuginea. Similarly, Leydig cells may communicate with Sertoli cells and germ cells of the seminiferous tubules. Leydig cells are a relatively stable, heterogeneous population of cells in the human testis which persists even in cases of impaired spermatogenesis, fibrosis and different pathological changes of the testis. This fact suggests that Leydig cells survive under unusual conditions due to precise regulatory systems which make them to a larger extent independent from the local homeostasis.Biomedical Reviews 1996; 6: 11-41

Publication guidelines for quality improvement in health care: evolution of the SQUIRE project

In 2005, draft guidelines were published for reporting studies of quality improvement interventions as the initial step in a consensus process for development of a more definitive version. This article contains the full revised version of the guidelines, which the authors refer to as SQUIRE (Standards for QUality Improvement Reporting Excellence). This paper also describes the consensus process, which included informal feedback from authors, editors and peer reviewers who used the guidelines; formal written commentaries; input from a group of publication guideline developers; ongoing review of the literature on the epistemology of improvement and methods for evaluating complex social programmes; a two-day meeting of stakeholders for critical discussion and debate of the guidelines’ content and wording; and commentary on sequential versions of the guidelines from an expert consultant group. Finally, the authors consider the major differences between SQUIRE and the initial draft guidelines; limitations of and unresolved questions about SQUIRE; ancillary supporting documents and alternative versions that are under development; and plans for dissemination, testing and further development of SQUIRE

Progenitor cells of the testosterone-producing Leydig cells revealed

The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair

A novel neurotrophic therapeutic strategy for experimental stroke.

Human chorionic gonadotropin (hCG) promotes proliferation of endogenous neural stem cells, and erythropoietin (EPO) promotes differentiation of these cells into neural stem cells. The current study examined effects of sequential administration of these two compounds, initiated 24 h after stroke. At that time, rats were randomized into four treatment groups: hCG+EPO (3 IM doses hCG over 5 days, followed by 3 IV doses EPO over 3 days), hCG+Saline using the same schedule, Saline+EPO using the same schedule, or neither drug (Saline+Saline). The primary endpoint was the composite neurological score, measured 11 times, from 1 h until 12 weeks post-insult. The neurological score was different across treatment groups (p<0.03). Pairwise testing of groups found that the hCG+EPO group had significantly better behavior at 6/10 post-stroke time points as compared to Saline+Saline. The differences observed when comparing the two-drug group with placebo were less apparent when comparing either of the one-drug groups with placebo. The two one-drug treatment arms did not significantly differ at any time point. Treatment with hCG+EPO significantly reduced total lesion volume by 82-89% compared to the other three treatment groups. The current therapeutic strategy improved behavioral outcome and reduced lesion volume with a time window of 24 h after the onset of stroke. The results from these experiments provide new insight into the effects of these two growth factors on stroke in rats, and could suggest a potential for translation into human stroke studies

Network synchronization: Optimal and Pessimal Scale-Free Topologies

By employing a recently introduced optimization algorithm we explicitely design optimally synchronizable (unweighted) networks for any given scale-free degree distribution. We explore how the optimization process affects degree-degree correlations and observe a generic tendency towards disassortativity. Still, we show that there is not a one-to-one correspondence between synchronizability and disassortativity. On the other hand, we study the nature of optimally un-synchronizable networks, that is, networks whose topology minimizes the range of stability of the synchronous state. The resulting ``pessimal networks'' turn out to have a highly assortative string-like structure. We also derive a rigorous lower bound for the Laplacian eigenvalue ratio controlling synchronizability, which helps understanding the impact of degree correlations on network synchronizability.Comment: 11 pages, 4 figs, submitted to J. Phys. A (proceedings of Complex Networks 2007

Optimal network topologies: Expanders, Cages, Ramanujan graphs, Entangled networks and all that

We report on some recent developments in the search for optimal network topologies. First we review some basic concepts on spectral graph theory, including adjacency and Laplacian matrices, and paying special attention to the topological implications of having large spectral gaps. We also introduce related concepts as ``expanders'', Ramanujan, and Cage graphs. Afterwards, we discuss two different dynamical feautures of networks: synchronizability and flow of random walkers and so that they are optimized if the corresponding Laplacian matrix have a large spectral gap. From this, we show, by developing a numerical optimization algorithm that maximum synchronizability and fast random walk spreading are obtained for a particular type of extremely homogeneous regular networks, with long loops and poor modular structure, that we call entangled networks. These turn out to be related to Ramanujan and Cage graphs. We argue also that these graphs are very good finite-size approximations to Bethe lattices, and provide almost or almost optimal solutions to many other problems as, for instance, searchability in the presence of congestion or performance of neural networks. Finally, we study how these results are modified when studying dynamical processes controlled by a normalized (weighted and directed) dynamics; much more heterogeneous graphs are optimal in this case. Finally, a critical discussion of the limitations and possible extensions of this work is presented.Comment: 17 pages. 11 figures. Small corrections and a new reference. Accepted for pub. in JSTA

Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren

<STRONG>Background</STRONG> Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation. <STRONG>Methods and Findings</STRONG> We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37–39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12–1.20; 33–36 wk adjusted OR 1.53, 95% CI 1.43–1.63; 28–32 wk adjusted OR 2.66, 95% CI 2.38–2.97; 24–27 wk adjusted OR 6.92, 95% CI 5.58–8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37–39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases. <STRONG>Conclusions</STRONG> Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery

Is adrenalectomy necessary during unilateral nephrectomy for Wilms Tumor? A report from the Children\u27s Oncology Group.

PURPOSE: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome. METHODS: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy. RESULTS: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially in 194 patients (5.2%). Of the adrenal glands removed, 68 (4.4%) contained tumor. Adrenal involvement was more common in patients with stage 3 (9.8%) than stage 2 disease (1.9%; p \u3c 0.0001). After controlling for stage and histopathology, five-year EFS was similar whether or not the adrenal gland was removed (p = 0.48), or involved with tumor (p = 0.81); however, intraoperative spill rates were higher in patients undergoing adrenalectomy (26.1% vs 15.5%, p \u3c 0.0001), likely due to larger tumor size or technical factors. No patient had clinical evidence of adrenal insufficiency or tumor recurrence in the adrenal gland during follow-up (median 9.9 years). CONCLUSIONS: Sparing the adrenal gland during nephrectomy for unilateral Wilms tumor was not associated with a higher incidence of intraoperative spill and was associated with a similar oncologic outcome, on a per-stage basis, with cases where the adrenal was removed. Thus, adrenalectomy should not be considered mandatory during radical nephrectomy for Wilms tumor