In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by ...leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT‐related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence‐based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease‐modifying therapeutic option. Novel treatments such as peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large fraction of patients.
The NEWS-G collaboration uses spherical proportional counters (SPCs) to search for weakly interacting massive particles (WIMPs). Here, in this paper, we report the first measurements of the nuclear ...quenching factor in neon gas at 2 bar using an SPC deployed in a neutron beam at the TUNL facility. The energy-dependence of the nuclear quenching factor is modeled using a simple power law: $αE^{β}_{nr}$; we determine its parameters by simultaneously fitting the data collected with the detector over a range of energies. We measured the following parameters in Ne : CH4 at 2 bar: α= 0.2801±0.0050 (fit) ±0.0045 (sys) and β=0.0867±0.020 (fit) ±0.006 (sys). Our measurements do not agree with expected values from SRIM or Lindhard theory. We demonstrated the feasibility of performing quenching factor measurements at sub-keV energies in gases using SPCs and a neutron beam.
P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We ...have characterized a PPC detector’s response to
α
particles incident on the sensitive passivated and p
+
surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the
Majorana
Demonstrator
experiment, a search for neutrinoless double-beta decay (
0
ν
β
β
) in
76
Ge.
α
decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of
α
identification, reliably identifying
α
background events on the passivated surface of the detector. We demonstrate effective rejection of all surface
α
events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the
0
ν
β
β
region of interest window by an order of magnitude in the
Majorana
Demonstrator
and will be used in the upcoming LEGEND-200 experiment.
Temporomandibular disorders Durham, Justin; Newton-John, Toby R O; Zakrzewska, Joanna M
BMJ (Online),
03/2015, Letnik:
350, Številka:
mar12 9
Journal Article, Book Review
Recenzirano
Odprti dostop
The bottom line TMDs represent a range of conditions with multifactorial complex pathophysiology, which are common up to the age of 40 years TMDs can present as a continuous or episodic pain of ...varying intensity around and in the ears radiating up to the temple or down the mandible to the neck Persistent (chronic) TMDs can be associated with other chronic pain conditions Early management with education and counselling is highly effective More complex patients or those with persistent TMDs require a biopsychosocial approach delivered by a multidisciplinary pain team After odontogenic pain, temporomandibular disorders (TMDs) are one of the most common causes of pain in the mouth and face and also have the potential to produce persisting (chronic) pain. 1 2 Chronic or persistent (myogenous) TMDs can be associated with other chronic pain conditions, 3 including migraine, fibromyalgia, and widespread pain. 4 5 6 7 8 They are also known to be comorbid with bruxism, depression, irritable bowel syndrome, and chronic fatigue. 6 9 10 With or without these comorbidities, TMDs are recognised to have a considerable impact on quality of life. 11 12 13 14 15 16 17 Sources and selection criteria We conducted a systematic search of Medline (1966 to 5 August 2014), PROSPERO, and Cochrane libraries for systematic reviews relating to interventions for TMDs.
Summary Background Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data ...suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. Methods In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m2 intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0–1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 μmol/mol creatinine vs ≥60 μmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with ClinicalTrials.gov , number NCT00744497. Findings Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19·0 months (IQR 11·2–25·1) and 914 patients had died. Median overall survival was 21·5 months (95% CI 20·3–22·8) in the dasatinib group and 21·2 months (20·0–23·4) in the placebo group (stratified hazard ratio HR 0·99, 95·5% CI 0·87–1·13; p=0·90). The most common grade 3–4 adverse events included diarrhoea (58 8% patients in the dasatinib group vs 27 4% patients in the placebo group), fatigue (62 8% vs 42 6%), and asthenia (40 5% vs 23 3%); grade 3–4 pleural effusions were uncommon (ten 1% vs three <1%). Interpretation The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. Funding Bristol-Myers Squibb.
The PHENIX Forward Silicon Vertex Detector Aidala, C.; Anaya, L.; Anderssen, E. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2014, Letnik:
755
Journal Article
Recenzirano
Odprti dostop
A new silicon detector has been developed to provide the PHENIX experiment with precise charged particle tracking at forward and backward rapidity. The Forward Silicon Vertex Tracker (FVTX) was ...installed in PHENIX prior to the 2012 run period of the Relativistic Heavy Ion Collider (RHIC). The FVTX is composed of two annular endcaps, each with four stations of silicon mini-strip sensors, covering a rapidity range of 1.2<|η|<2.2 that closely matches the two existing PHENIX muon arms. Each station consists of 48 individual silicon sensors, each of which contains two columns of mini-strips with 75μm pitch in the radial direction and lengths in the ϕ direction varying from 3.4mm at the inner radius to 11.5mm at the outer radius. The FVTX has approximately 0.54million strips in each endcap. These are read out with FPHX chips, developed in collaboration with Fermilab, which are wire bonded directly to the mini-strips. The maximum strip occupancy reached in central Au–Au collisions is approximately 2.8%. The precision tracking provided by this device makes the identification of muons from secondary vertices away from the primary event vertex possible. The expected distance of closest approach (DCA) resolution of 200μm or better for particles with a transverse momentum of 5 GeV/c will allow identification of muons from relatively long-lived particles, such as D and B mesons, through their broader DCA distributions.
Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of ...two-, four-, and six-particle angular correlations in d+Au collisions at sqrts_{NN}=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrts_{NN}=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.
Seventy mortalities of North Atlantic right whales Eubalaena glacialis (NARW) were documented between 2003 and 2018 from Florida, USA, to the Gulf of St. Lawrence, Canada. These included 29 adults, ...14 juveniles, 10 calves, and 17 of unknown age class. Females represented 65.5% (19/29) of known-sex adults. Fourteen cases had photos only; 56 carcasses received external examinations, 44 of which were also necropsied. Cause of death was determined in 43 cases, of which 38 (88.4%) were due to anthropogenic trauma: 22 (57.9%) from entanglement, and 16 (42.1%) from vessel strike. Gross and histopathologic lesions associated with entanglement were often severe and included deep lacerations caused by constricting line wraps around the flippers, flukes, and head/mouth; baleen plate mutilation; chronic extensive bone lesions from impinging line, and traumatic scoliosis resulting in compromised mobility in a calf. Chronically entangled whales were often in poor body condition and had increased cyamid burden, reflecting compromised health. Vessel strike blunt force injuries included skull and vertebral fractures, blubber and muscle contusions, and large blood clots. Propeller-induced wounds often caused extensive damage to blubber, muscle, viscera, and bone. Overall prevalence of NARW entanglement mortalities increased from 21% (1970-2002) to 51% during this study period. This demonstrates that despite mitigation efforts, entanglements and vessel strikes continue to inflict profound physical trauma and suffering on individual NARWs. These cumulative mortalities are also unsustainable at the population level, so urgent and aggressive intervention is needed to end anthropogenic mortality in this critically endangered species.
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