Human helminth therapy to treat inflammatory disorders - where do we stand?

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans

Vocal Communications and the Maintenance of Population Specific Songs in a Contact Zone

Bird song has been hypothesized to play a role in several important aspects of the biology of songbirds, including the generation of taxonomic diversity by speciation; however, the role that song plays in speciation within this group may be dependent upon the ability of populations to maintain population specific songs or calls in the face of gene flow and external cultural influences. Here, in an exploratory study, we construct a spatially explicit model of population movement to examine the consequences of secondary contact of populations singing distinct songs. We concentrate on two broad questions: 1) will population specific songs be maintained in a contact zone or will they be replaced by shared song, and 2) what spatial patterns in the distribution of songs may result from contact? We examine the effects of multiple factors including song-based mating preferences and movement probabilities, oblique versus paternal learning of song, and both cultural and genetic mutations. We find a variety of conditions under which population specific songs can be maintained, particularly when females have preferences for their population specific songs, and we document many distinct patterns of song distribution within the contact zone, including clines, banding, and mosaics

Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

Brain computer tomography in critically ill patients -- a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Brain computer tomography (brain CT) is an important imaging tool in patients with intracranial disorders. In ICU patients, a brain CT implies an intrahospital transport which has inherent risks. The proceeds and consequences of a brain CT in a critically ill patient should outweigh these risks. The aim of this study was to critically evaluate the diagnostic and therapeutic yield of brain CT in ICU patients.</p> <p>Methods</p> <p>In a prospective observational study data were collected during one year on the reasons to request a brain CT, expected abnormalities, abnormalities found by the radiologist and consequences for treatment. An “expected abnormality” was any finding that had been predicted by the physician requesting the brain CT. A brain CT was “diagnostically positive”, if the abnormality found was new or if an already known abnormality was increased. It was “diagnostically negative” if an already known abnormality was unchanged or if an expected abnormality was not found. The treatment consequences of the brain CT, were registered as “treatment as planned”, “treatment changed, not as planned”, “treatment unchanged”.</p> <p>Results</p> <p>Data of 225 brain CT in 175 patients were analyzed. In 115 (51%) brain CT the abnormalities found were new or increased known abnormalities. 115 (51%) brain CT were found to be diagnostically positive. In the medical group 29 (39%) of brain CT were positive, in the surgical group 86 (57%), <it>p</it> 0.01. After a positive brain CT, in which the expected abnormalities were found, treatment was changed as planned in 33%, and in 19% treatment was changed otherwise than planned.</p> <p>Conclusions</p> <p>The results of this study show that the diagnostic and therapeutic yield of brain CT in critically ill patients is moderate. The development of guidelines regarding the decision rules for performing a brain CT in ICU patients is needed.</p

Pressure transduction and fluid evacuation during conventional negative pressure wound therapy of the open abdomen and NPWT using a protective disc over the intestines

<p>Abstract</p> <p>Background</p> <p>Negative pressure wound therapy (NPWT) has gained acceptance among surgeons, for the treatment of open abdomen, since very high closure rates have been reported with this method, compared to other kinds of wound management for the open abdomen. However, the method has occasionally been associated with increased development of fistulae. We have previously shown that NPWT induces ischemia in the underlying small intestines close to the vacuum source, and that a protective disc placed between the intestines and the vacuum source prevents the induction of ischemia. In this study we compare pressure transduction and fluid evacuation of the open abdomen with conventional NPWT and NPWT with a protective disc.</p> <p>Methods</p> <p>Six pigs underwent midline incision and the application of conventional NPWT and NPWT with a protective disc between the intestines and the vacuum source. The pressure transduction was measured centrally beneath the dressing, and at the anterior abdominal wall, before and after the application of topical negative pressures of -50, -70 and -120 mmHg. The drainage of fluid from the abdomen was measured, with and without the protective disc.</p> <p>Results</p> <p>Abdominal drainage was significantly better (p < 0. 001) using NPWT with the protective disc at -120 mmHg (439 ± 25 ml vs. 239 ± 31 ml), at -70 mmHg (341 ± 27 ml vs. 166 ± 9 ml) and at -50 mmHg (350 ± 50 ml vs. 151 ± 21 ml) than with conventional NPWT. The pressure transduction was more even at all pressure levels using NPWT with the protective disc than with conventional NPWT.</p> <p>Conclusions</p> <p>The drainage of the open abdomen was significantly more effective when using NWPT with the protective disc than with conventional NWPT. This is believed to be due to the more even and effective pressure transduction in the open abdomen using a protective disc in combination with NPWT.</p

Microvascular blood flow response in the intestinal wall and the omentum during negative wound pressure therapy of the open abdomen

PURPOSE: Higher closure rates of the open abdomen have been reported with negative pressure wound therapy (NPWT) compared with other wound therapy techniques. However, the method has occasionally been associated with increased development of intestinal fistulae. The present study measures microvascular blood flow in the intestinal wall and the omentum before and during NPWT. METHODS: Six pigs underwent midline incision and application of NPWT to the open abdomen. The microvascular blood flow in the underlying intestinal loop wall and the omentum was recorded before and after the application of NPWT of -50, -70, -100, -120, -150, and -170 mmHg respectively, using laser Doppler velocimetry. RESULTS: A significant decrease in microvascular blood flow was seen in the intestinal wall during application of all negative pressures levels. The blood flow was 2.7 (±0.2) Perfusion Units (PU) before and 2.0 (±0.2) PU (*p < 0.05) after application of -50 mmHg, and 3.6 (±0.6) PU before and 1.5 (±0.2) PU (**p < 0.01) after application of -170 mmHg. CONCLUSIONS: In the present study, we show that negative pressures between -50 and -170 mmHg induce a significant decrease in the microvascular blood flow in the intestinal wall. The decrease in blood flow increased with the amount of negative pressure applied. One can only speculate that a longstanding decreased blood flow in the intestinal wall may induce ischemia and secondary necrosis in the intestinal wall, which, theoretically, could promote the development of intestinal fistulae. We believe that NPWT of the open abdomen is a very effective treatment but could probably be improved

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT