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Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.
Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development
A Snapshot of J. L. Synge
A brief description is given of the life and influence on relativity theory
of Professor J. L. Synge accompanied by some technical examples to illustrate
his style of work
Knee surgery and its evidence base
Introduction Evidence driven orthopaedics is gaining prominence. It enables better management decisions and therefore better patient care. The aim of our study was to review a selection of the leading publications pertaining to knee surgery to assess changes in levels of evidence over a decade. Methods Articles from the years 2000 and 2010 in The Knee, the Journal of Arthroplasty, Knee Surgery, Sports Traumatology, Arthroscopy, the Journal of Bone and Joint Surgery (American Volume) and the Bone and Joint Journal were analysed and ranked according to guidelines from the Centre for Evidence-Based Medicine. The intervening years (2003, 2005 and 2007) were also analysed to further define the trend. Results The percentage of high level evidence (level I and II) studies increased albeit without reaching statistical significance. Following a significant downward trend, the latter part of the decade saw a major rise in levels of published evidence. The most frequent type of study was therapeutic. Conclusions Although the rise in levels of evidence across the decade was not statistically significant, there was a significant drop and then rise in these levels in the interim. It is therefore important that a further study is performed to assess longer-term trends. Recent developments have made clear that high quality evidence will be having an ever increasing influence on future orthopaedic practice. We suggest that journals implement compulsory declaration of a published study's level of evidence and that authors consider their study designs carefully to enhance the quality of available evidence
Hierarchies of Susy Splittings and Invisible Photinos as Dark Matter
We explore how to generate hierarchies in the splittings between
superpartners. Some of the consequences are the existence of invisible
components of dark matter, new inflaton candidates, invisible monopoles and a
number of invisible particles that might dominate during various eras, in
particular between BBN and recombination and decay subsequently.Comment: 16 pages. v3: Ref. 27 has been modified. v4: Published versio
Light dark matter and dark force at colliders
Light Dark Matter, GeV, with sizable direct detection rate is an
interesting and less explored scenario. Collider searches can be very powerful,
such as through the channel in which a pair of dark matter particle are
produced in association with a jet. It is a generic possibility that the
mediator of the interaction between DM and the nucleus will also be accessible
at the Tevatron and the LHC. Therefore, collider search of the mediator can
provide a more comprehensive probe of the dark matter and its interactions. In
this article, to demonstrate the complementarity of these two approaches, we
focus on the possibility of the mediator being a new gauge boson, which
is probably the simplest model which allows a large direct detection cross
section for a light dark matter candidate. We combine searches in the
monojet+MET channel and dijet resonance search for the mediator. We find that
for the mass of between 250 GeV and 4 TeV, resonance searches at the
colliders provide stronger constraints on this model than the monojet+MET
searches.Comment: 23 pages and 14 figure
Catastrophizing mediates the relationship between the personal belief in a just world and pain outcomes among chronic pain support group attendees
Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to one’s own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made
Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.
OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock.
METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact.
RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring.
CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock
Maverick dark matter at colliders
Assuming that dark matter is a weakly interacting massive particle (WIMP)
species X produced in the early Universe as a cold thermal relic, we study the
collider signal of pp or ppbar -> XXbar + jets and its distinguishability from
standard-model background processes associated with jets and missing energy. We
assume that the WIMP is the sole particle related to dark matter within reach
of the LHC--a "maverick" particle--and that it couples to quarks through a
higher dimensional contact interaction. We simulate the WIMP final-state signal
XXbar + jet and dominant standard-model (SM) background processes and find that
the dark-matter production process results in higher energies for the colored
final state partons than do the standard-model background processes, resulting
in more QCD radiation and a higher jet multiplicity. As a consequence, the
detectable signature of maverick dark matter is an excess over standard-model
expectations of events consisting of large missing transverse energy, together
with large leading jet transverse momentum and scalar sum of the transverse
momenta of the jets. Existing Tevatron data and forthcoming LHC data can
constrain (or discover!) maverick dark matter.Comment: 11 pages, 7 figure
The gravitino coupling to broken gauge theories applied to the MSSM
We consider gravitino couplings in theories with broken gauge symmetries. In
particular, we compute the single gravitino production cross section in W+ W-
fusion processes. Despite recent claims to the contrary, we show that this
process is always subdominant to gluon fusion processes in the high energy
limit. The full calculation is performed numerically; however, we give analytic
expressions for the cross section in the supersymmetric and electroweak limits.
We also confirm these results with the use of the effective theory of goldstino
interactions.Comment: 26 pages, 4 figure
Neural development features: Spatio-temporal development of the Caenorhabditis elegans neuronal network
The nematode Caenorhabditis elegans, with information on neural connectivity,
three-dimensional position and cell linage provides a unique system for
understanding the development of neural networks. Although C. elegans has been
widely studied in the past, we present the first statistical study from a
developmental perspective, with findings that raise interesting suggestions on
the establishment of long-distance connections and network hubs. Here, we
analyze the neuro-development for temporal and spatial features, using birth
times of neurons and their three-dimensional positions. Comparisons of growth
in C. elegans with random spatial network growth highlight two findings
relevant to neural network development. First, most neurons which are linked by
long-distance connections are born around the same time and early on,
suggesting the possibility of early contact or interaction between connected
neurons during development. Second, early-born neurons are more highly
connected (tendency to form hubs) than later born neurons. This indicates that
the longer time frame available to them might underlie high connectivity. Both
outcomes are not observed for random connection formation. The study finds that
around one-third of electrically coupled long-range connections are late
forming, raising the question of what mechanisms are involved in ensuring their
accuracy, particularly in light of the extremely invariant connectivity
observed in C. elegans. In conclusion, the sequence of neural network
development highlights the possibility of early contact or interaction in
securing long-distance and high-degree connectivity
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