1,072 research outputs found
Commentary on strategies for switching antipsychotics
Both the new generation of antipsychotics and the more traditional antipsychotic drugs produce an important and meaningful improvement in patients with schizophrenia, but most patients are neither cured nor free of symptoms. As a consequence, it is common to switch from one drug to another in the hope of obtaining a better response. All antipsychotic drugs produce some side effects, so switching can also be a tolerance issue. There are reports in the literature on the tactics of switching: abrupt discontinuation, cross tapering, starting a patient on a new drug while continuing with the old drug until the new drug has reached a steady state, or some variation on these tactics. In this issue, Ganguli et al. have carried out a randomized switching study, the data from which indicates the tactics that might be optimal. We put this paper into context, provide a critique and describe indications for switching
A massive, quiescent galaxy at redshift of z=3.717
In the early Universe finding massive galaxies that have stopped forming
stars present an observational challenge as their rest-frame ultraviolet
emission is negligible and they can only be reliably identified by extremely
deep near-infrared surveys. These have revealed the presence of massive,
quiescent early-type galaxies appearing in the universe as early as z2,
an epoch 3 Gyr after the Big Bang. Their age and formation processes have now
been explained by an improved generation of galaxy formation models where they
form rapidly at z3-4, consistent with the typical masses and ages derived
from their observations. Deeper surveys have now reported evidence for
populations of massive, quiescent galaxies at even higher redshifts and earlier
times, however the evidence for their existence, and redshift, has relied
entirely on coarsely sampled photometry. These early massive, quiescent
galaxies are not predicted by the latest generation of theoretical models.
Here, we report the spectroscopic confirmation of one of these galaxies at
redshift z=3.717 with a stellar mass of 1.710 M whose
absorption line spectrum shows no current star-formation and which has a
derived age of nearly half the age of the Universe at this redshift. The
observations demonstrates that the galaxy must have quickly formed the majority
of its stars within the first billion years of cosmic history in an extreme and
short starburst. This ancestral event is similar to those starting to be found
by sub-mm wavelength surveys pointing to a possible connection between these
two populations. Early formation of such massive systems is likely to require
significant revisions to our picture of early galaxy assembly.Comment: 6 pages, 7 figures. This is the final preprint corresponding closely
to the published version. Uploaded 6 months after publication in accordance
with Nature polic
Compromized geranylgeranylation of RhoA and Rac1 in mevalonate kinase deficiency
Mevalonate kinase deficiency (MKD) is an autoinflammatory disorder caused by mutations in the MVK gene resulting in decreased activity of the enzyme mevalonate kinase (MK). Although MK is required for biosynthesis of all isoprenoids, in MKD, in particular, the timely synthesis of geranylgeranyl pyrophosphate appears to be compromised. Because small guanosine triphosphatases (GTPases) depend on geranylgeranylation for their proper signaling function, we studied the effect of MK deficiency on geranylgeranylation and activation of the two small GTPases, RhoA and Rac1. We demonstrate that both geranylgeranylation and activation of the two GTPases are more easily disturbed in MKD cells than in control cells when the flux though the isoprenoid biosynthesis pathway is suppressed by low concentrations of simvastatin. The limited capacity of geranylgeranylation in MKD cells readily leads to markedly increased levels of nonisoprenylated and activated GTPases, which will affect proper signaling by these GTPases
The rapid assembly of an elliptical galaxy of 400 billion solar masses at a redshift of 2.3
Stellar archeology shows that massive elliptical galaxies today formed
rapidly about ten billion years ago with star formation rates above several
hundreds solar masses per year (M_sun/yr). Their progenitors are likely the
sub-millimeter-bright galaxies (SMGs) at redshifts (z) greater than 2. While
SMGs' mean molecular gas mass of 5x10^10 M_sun can explain the formation of
typical elliptical galaxies, it is inadequate to form ellipticals that already
have stellar masses above 2x10^11 M_sun at z ~ 2. Here we report
multi-wavelength high-resolution observations of a rare merger of two massive
SMGs at z = 2.3. The system is currently forming stars at a tremendous rate of
2,000 M_sun/yr. With a star formation efficiency an order-of-magnitude greater
than that of normal galaxies, it will quench the star formation by exhausting
the gas reservoir in only ~200 million years. At a projected separation of 19
kiloparsecs, the two massive starbursts are about to merge and form a passive
elliptical galaxy with a stellar mass of ~4x10^11 M_sun. Our observations show
that gas-rich major galaxy mergers, concurrent with intense star formation, can
form the most massive elliptical galaxies by z ~ 1.5.Comment: Appearing in Nature online on May 22 and in print on May 30.
Submitted here is the accepted version (including the Supplementary
Information), see nature.com for the final versio
AMI-LA observations of the SuperCLASS supercluster
We present a deep survey of the SuperCLASS super-cluster - a region of sky
known to contain five Abell clusters at redshift - performed using
the Arcminute Microkelvin Imager (AMI) Large Array (LA) at 15.5GHz. Our
survey covers an area of approximately 0.9 square degrees. We achieve a nominal
sensitivity of Jy beam toward the field centre, finding 80
sources above a threshold. We derive the radio colour-colour
distribution for sources common to three surveys that cover the field and
identify three sources with strongly curved spectra - a high-frequency-peaked
source and two GHz-peaked-spectrum sources. The differential source count (i)
agrees well with previous deep radio source count, (ii) exhibits no evidence of
an emerging population of star-forming galaxies, down to a limit of 0.24mJy,
and (iii) disagrees with some models of the 15GHz source population.
However, our source count is in agreement with recent work that provides an
analytical correction to the source count from the SKADS Simulated Sky,
supporting the suggestion that this discrepancy is caused by an abundance of
flat-spectrum galaxy cores as-yet not included in source population models
Central modulation in cluster headache patients treated with occipital nerve stimulation: an FDG-PET study
Peer reviewe
Contrasting Patterns of Coral Bleaching Susceptibility in 2010 Suggest an Adaptive Response to Thermal Stress
Background: \ud
Coral bleaching events vary in severity, however, to date, the hierarchy of susceptibility to bleaching among coral taxa has been consistent over a broad geographic range and among bleaching episodes. Here we examine the extent of spatial and temporal variation in thermal tolerance among scleractinian coral taxa and between locations during the 2010 thermally induced, large-scale bleaching event in South East Asia.\ud
\ud
Methodology/Principal Findings: \ud
Surveys to estimate the bleaching and mortality indices of coral genera were carried out at three locations with contrasting thermal and bleaching histories. Despite the magnitude of thermal stress being similar among locations in 2010, there was a remarkable contrast in the patterns of bleaching susceptibility. Comparisons of bleaching susceptibility within coral taxa and among locations revealed no significant differences between locations with similar thermal histories, but significant differences between locations with contrasting thermal histories (Friedman = 34.97; p,0.001). Bleaching was much less severe at locations that bleached during 1998, that had greater historical temperature variability and lower rates of warming. Remarkably, Acropora and Pocillopora, taxa that are typically highly susceptible, although among the most susceptible in Pulau Weh (Sumatra, Indonesia) where respectively, 94% and 87% of colonies died, were among the least susceptible in Singapore, where only 5% and 12% of colonies died.\ud
\ud
Conclusions/Significance: \ud
The pattern of susceptibility among coral genera documented here is unprecedented. A parsimonious explanation for these results is that coral populations that bleached during the last major warming event in 1998 have adapted and/or acclimatised to thermal stress. These data also lend support to the hypothesis that corals in regions subject to more variable temperature regimes are more resistant to thermal stress than those in less variable environments
Chronic non-specific low back pain - sub-groups or a single mechanism?
Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a
considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions
for chronic non-specific low back pain indicate limited effectiveness for most commonly applied
interventions and approaches.
Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of
effectiveness is at odds with their clinical experience of managing patients with back pain. A
common explanation for this discrepancy is the perceived heterogeneity of patients with chronic
non-specific low back pain. It is felt that the effects of treatment may be diluted by the application
of a single intervention to a complex, heterogeneous group with diverse treatment needs. This
argument presupposes that current treatment is effective when applied to the correct patient.
An alternative perspective is that the clinical trials are correct and current treatments have limited
efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important
that the sub-grouping paradigm is closely examined. This paper argues that there are numerous
problems with the sub-grouping approach and that it may not be an important reason for the
disappointing results of clinical trials. We propose instead that current treatment may be ineffective
because it has been misdirected. Recent evidence that demonstrates changes within the brain in
chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of
cortical reorganisation and degeneration. This perspective offers interesting insights into the
chronic low back pain experience and suggests alternative models of intervention.
Summary: The disappointing results of clinical research are commonly explained by the failure of
researchers to adequately attend to sub-grouping of the chronic non-specific low back pain
population. Alternatively, current approaches may be ineffective and clinicians and researchers may
need to radically rethink the nature of the problem and how it should best be managed
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