A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

© 2016 cThe Author(s). Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases

Neoadjuvant chemotherapy in the setting of locally advanced olfactory neuroblastoma with intracranial extension

Olfactory neuroblastoma (esthesioneuroblastoma) is a rare malignant tumor of neuroectodermal origin. With only about 1,000 cases reported, there are no clear guidelines regarding management of this disease. Intracranial extension and orbital involvement have been shown to be independent risk factors associated with poorer outcomes. We hereby report a case of a 46-year old male presented with an 8-month history of progressive nasal obstruction and intermittent right-sided epistaxis associated with anosmia and increased pressure sensation in and around the right eye. Further evaluation revealed a large enhancing heterogeneous cystic and solid mass in the right nasal cavity measuring 5.0×5.3×4.6 cm with extension superiorly into the anterior cranial fossa and frontal lobes, ethmoid and sphenoid sinuses. A biopsy of this mass confirmed high grade olfactory neuroblastoma. Because of the intra-cranial extension, a decision was made to start neoadjuvant chemotherapy with cisplatin and etoposide. The patient had very good response to this treatment on a repeat imaging study and went on to have resection of this mass. Post-operatively, he received radiation therapy to the tumor bed and 2 more cycles of chemotherapy. He has been followed now for more than 8 months with no evidence of disease recurrence

Associations between partial sickness benefit and disability pensions: initial findings of a Finnish nationwide register study

<p>Abstract</p> <p>Background</p> <p>Timely return to work after longterm sickness absence and the increased use of flexible work arrangements together with partial health-related benefits are tools intended to increase participation in work life. Although partial sickness benefit and partial disability pension are used in many countries, prospective studies on their use are largely lacking. Partial sickness benefit was introduced in Finland in 2007. This register study aimed to investigate the use of health-related benefits by subjects with prolonged sickness absence, initially on either partial or full sick leave.</p> <p>Methods</p> <p>Representative population data (13 375 men and 16 052 women either on partial or full sick leave in 2007) were drawn from national registers and followed over an average of 18 months. The registers provided information on the study outcomes: diagnoses and days of payment for compensated sick leaves, and the occurrence of disability pension. Survival analysis and multinomial regression were carried out using sociodemographic variables and prior sickness absence as covariates.</p> <p>Results</p> <p>Approximately 60% of subjects on partial sick leave and 30% of those on full sick leave had at least one recurrent sick leave over the follow up. A larger proportion of those on partial sick leave (16%) compared to those on full sick leave (1%) had their first recurrent sick leave during the first month of follow up. The adjusted risks of the first recurrent sick leave were 1.8 and 1.7 for men and women, respectively, when subjects on partial sick leave were compared with those on full sick leave. There was no increased risk when those with their first recurrent sick leave in the first month were excluded from the analyses. The risks of a full disability pension were smaller and risks of a partial disability pension approximately two-fold among men and women initially on partial sick leave, compared to subjects on full sick leave.</p> <p>Conclusions</p> <p>This is the first follow up study of the newly adopted partial sickness benefit in Finland. The results show that compared to full sick leave, partial sick leave - when not followed by lasting return to work - is more typically followed by partial disability pension and less frequently by full disability pension. It is anticipated that the use of partial benefits in connection with part-time participation in work life will have favourable effects on future disability pension rates in Finland.</p

The antibacterial activity of acetic acid against biofilm-producing pathogens of relevance to burns patients

Introduction: Localised infections, and burn wound sepsis are key concerns in the treatment of burns patients, and prevention of colonisation largely relies on biocides. Acetic acid has been shown to have good antibacterial activity against various planktonic organisms, however data is limited on efficacy, and few studies have been performed on biofilms. Objectives: We sought to investigate the antibacterial activity of acetic acid against important burn wound colonising organisms growing planktonically and as biofilms. Methods: Laboratory experiments were performed to test the ability of acetic acid to inhibit growth of pathogens, inhibit the formation of biofilms, and eradicate pre-formed biofilms. Results: Twenty-nine isolates of common wound-infecting pathogens were tested. Acetic acid was antibacterial against planktonic growth, with an minimum inhibitory concentration of 0.16-0.31% for all isolates, and was also able to prevent formation of biofilms (at 0.31 %). Eradication of mature biofilms was observed for all isolates after three hours of exposure. Conclusions: This study provides evidence that acetic acid can inhibit growth of key burn wound pathogens when used at very dilute concentrations. Owing to current concerns of the reducing efficacy of systemic antibiotics, this novel biocide application offers great promise as a cheap and effective measure to treat infections in burns patients

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

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration