The Heterodyne Instrument for the Far Infrared (HIFI) onboard the Herschel Space Observatory allows the first observations of light diatomic molecules at high spectral resolution and in multiple ...transitions. Here, we report deep integrations using HIFI in different lines of hydrides towards the high-mass star forming region AFGL 2591. Detected are CH, CH+, NH, OH+, H2O+, while NH+ and SH+ have not been detected. All molecules except for CH and CH+ are seen in absorption with low excitation temperatures and at velocities different from the systemic velocity of the protostellar envelope. Surprisingly, the CH(JF,P = 3/22,- - 1/21,+ ) and CH+(J = 1-0, J = 2-1) lines are detected in emission at the systemic velocity. We can assign the absorption features to a foreground cloud and an outflow lobe, while the CH and CH+ emission stems from the envelope. The observed abundance and excitation of CH and CH+ can be explained in the scenario of FUV irradiated outflow walls, where a cavity etched out by the outflow allows protostellar FUV photons to irradiate and heat the envelope at larger distances driving the chemical reactions that produce these molecules. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Apppendices and Table 1 (pages 6 to 7) are only available in electronic form at http://www.aanda.org
Antihydrogen holds the promise to test, for the first time, the universality of free-fall with a system composed entirely of antiparticles. The AEgIS experiment at CERN’s antiproton decelerator aims ...to measure the gravitational interaction between matter and antimatter by measuring the deflection of a beam of antihydrogen in the Earths gravitational field (
g
¯
). The principle of the experiment is as follows: cold antihydrogen atoms are synthesized in a Penning-Malberg trap and are Stark accelerated towards a moiré deflectometer, the classical counterpart of an atom interferometer, and annihilate on a position sensitive detector. Crucial to the success of the experiment is the spatial precision of the position sensitive detector. We propose a novel free-fall detector based on a hybrid of two technologies: emulsion detectors, which have an intrinsic spatial resolution of 50 nm but no temporal information, and a silicon strip / scintillating fiber tracker to provide timing and positional information. In 2012 we tested emulsion films in vacuum with antiprotons from CERN’s antiproton decelerator. The annihilation vertices could be observed directly on the emulsion surface using the microscope facility available at the University of Bern. The annihilation vertices were successfully reconstructed with a resolution of 1–2 μmon the impact parameter. If such a precision can be realized in the final detector, Monte Carlo simulations suggest of order 500 antihydrogen annihilations will be sufficient to determine
g
¯
with a 1 % accuracy. This paper presents current research towards the development of this technology for use in the AEgIS apparatus and prospects for the realization of the final detector.
To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).
This three-part, randomised, ...placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab.
In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY).
Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis.
NCT00988221.
The beneficial effects of treatment and rehabilitation of patients with acute stroke in a dedicated stroke unit (SU) are well established. We wanted to examine if these effects are limited to certain ...groups of patients or if they apply to all patients independent of age, sex, comorbidity, and initial stroke severity.
This was a community-based study of outcome in 1241 consecutive stroke patients from 2 communities in Copenhagen: In one (Frederiksberg), treatment and rehabilitation were given in general neurological and medical wards (GW), and in the other (Bispebjerg) in one single large SU. Outcome measures were initial, 1-year, and 5-year mortality rates, a poor outcome (initial death or discharge to a nursing home), and length of hospital stay (LOHS). Multivariate regression analyses were used to examine the independent effect of SU treatment on the various subgroups.
The relative risks of initial death, poor outcome, and 1-year and 5-year mortality rates were reduced by 40% on average in patients treated in the SU compared with the GW. A beneficial effect of SU treatment was observed regardless of the patient's age, sex, comorbidity, and initial stroke severity. Those who benefited most appeared to be the patients with the most severe strokes (poor outcome: OR 0.17; 95% CI 0.05 to 0.58). Those who benefited least were patients with mild or moderate strokes (poor outcome: OR 0.66; 95% CI 0.41 to 0.98) and patients <75 years of age (poor outcome: OR 0.66; 95% CI 0.36 to 1.19). LOHS was reduced by 2 to 3 weeks in all who had their treatment in the SU except in patients with the most severe strokes. LOHS in these patients was similar to LOHS in the GW.
A beneficial effect of treatment in a SU is achieved in completely unselected patients independent of their age, sex, comorbidity, and stroke severity. Those who had the most severe strokes appeared to benefit most. All patients with acute stroke should therefore have access to treatment and rehabilitation in a dedicated SU.
Two or three weekly, daytime intramuscular injections of GH has been the traditional treatment of GH deficiency since the first studies. A recent reevaluation of the feasibility of subcutaneous GH ...injections revealed no side-effects, but a very strong preference by the patients for the subcutaneous route, and also an increase in growth rate in studies where the patients received daily injections given in the evening. That could indicate that the route, frequency and timing of GH administration may be of clinical importance. Subcutaneous injections result in a slower absorption, a smaller peak value, and a prolonged serum disappearance phase compared to intramuscular injections. This extends the periods of elevated serum GH levels in the patient, which might be advantageous. On the other hand, a reduced bioavailability of GH by the subcutaneous route has also been reported. The frequency of subcutaneous injections correlates positively with growth rate in animal studies. This is commonly ascribed to a closer resemblance to the endogenous pulsatile pattern. However, frequent subcutaneous injections do not induce a pulsatile pattern, but a pattern which is intermediary between continuous and true pulsatile administration. In a short-term patient study, we observed that pulsatile and continuous intravenous administration of GH generated identical increases in serum insulin-like growth factor I, which suggests that both pulsatory and constant, small elevations in serum GH are important for its actions. Concerning the time of administration, evening GH injections yield a more physiological pattern, and it has been shown that evening GH administration induces increased nitrogen retention and is more successful in normalizing circadian patterns of pertinent hormones and metabolites.
Polymer-coated liposomes can act as versatile drug-delivery systems due to long vascular circulation time and passive targeting by leaky blood vessels in diseased tissue. We present an experimental ...model system illustrating a new principle for improved and programmable drug-delivery, which takes advantage of an elevated activity of secretory phospholipase A(2) (PLA(2)) at the diseased target tissue. The secretory PLA(2) hydrolyses a lipid-based proenhancer in the carrier liposome, producing lyso-phospholipids and free fatty acids, which are shown in a synergistic way to lead to enhanced liposome destabilization and drug release at the same time as the permeability of the target membrane is enhanced. Moreover, the proposed system can be made thermosensitive and offers a rational way for developing smart liposome-based drug delivery systems. This can be achieved by incorporating specific lipid-based proenhancers or prodestabilisers into the liposome carrier, which automatically becomes activated by PLA(2) only at the diseased target sites, such as inflamed or cancerous tissue.
Abstract
Background
Pain is commonly reported in IBD patients, and evidence suggests a multifactorial aetiology. Vitamin D deficiency is known to cause muscle pain, but the influence of vitamin D on ...pain in IBD patients is unknown. The aim of this study was to investigate a possible association between vitamin D levels and pain severity in IBD patients.
Methods
Participants were recruited from nine hospitals in Norway from March 2013 to April 2014. Clinical data were collected by interview and from medical records. The Brief Pain Inventory (BPI) questionnaire was used to measure pain. To explore the possible association between vitamin D levels and pain severity, linear regression models were fitted.
Results
In total, 407 patients were included, 229 (56 %) with Crohn′s disease (CD) and 178 (44 %) with ulcerative colitis (UC). Vitamin D deficiency (25-OH-D < 50 nmol/l) was present in 125 (55 %) of CD patients and 78 (44 %) of UC patients. Pain other than everyday kinds of pain was reported in 182/407 patients (45%), most commonly in the abdomen, back and joints, and was more frequently reported with higher disease activity scores (SCCAI and HBI). In multivariate analysis adjusted for age, gender and disease activity, there was no association between vitamin D levels and pain severity. Higher pain severity scores were significantly associated with female gender in both UC (B 3.06; 95% CI 0.60, 5.53) and CD (B 3.26; 95% CI 1.44, 5.08). There was a trend towards lesser pain severity with 25-OH-D > 75 nmol/l in CD (B −2.42; 95% CI −5.06, 0.23), but not in UC.
Conclusions
Pain is commonly reported, followed by more active disease. In this study, female patients reported more severe pain. We found no association between pain severity and vitamin D deficiency, but higher levels of 25-OH-D may influence the experience of pain.
Abstract
The radar network deployed in southern France during the first special observing period (SOP 1) of the Hydrological Cycle in the Mediterranean Experiment (HyMeX) was designed to precisely ...document the 3D structure of moist upstream flow impinging on complex terrain as a function of time, height, and along-barrier distance, and surface rainfall patterns associated with orographic precipitation events. This deployment represents one of the most ambitious field experiments yet, endeavoring to collect high-quality observations of thunderstorms and precipitation systems developing over and in the vicinity of a major mountain chain.
Radar observations collected during HyMeX represent a valuable, and potentially unique, dataset that will be used to improve our knowledge of physical processes at play within coastal orographic heavy precipitating systems and to develop, and evaluate, novel radar-based products for research and operational activities. This article provides a concise description of this radar network and discusses innovative research ideas based upon preliminary analyses of radar observations collected during this field project with emphasis on the synergetic use of dual-polarimetric radar measurements collected at multiple frequencies.
Occurrence, composition and biolability of total dissolved nitrogen (TDN, including dissolved inorganic and organic N (DIN and DON) were examined in May and July 1996 in the northern (Köiguste ...transect) and southern part (Saulkrasti transect) of the Gulf of Riga. In the Saulkrasti transect, the Daugava River was a major source of TDN as indicated by concentrations of up to 60 μM TDN in the river plume, compared to about 20 μM TDN in the open gulf. DON made up 80 to 90% of the TDN, but on May 16 a nitrate-rich river plume lowered the proportion of DON to 65%. Riverine DIN and DON stimulated the biological activity along the transect in May, but apparently not in July. In the Köiguste transect, concentrations of TDN were 0.5-fold lower than at Saulkrasti. In May, input of terrestrial nutrients to the inner part of the transect probably increased the biological production. In both transects, the labile DON fraction, defined as bacterial DON degradation over a week, was estimated at 4 to 29%, with an average of 13%. Dissolved combined amino acids (DCAA) made up 10 to 30% of the DON. A high DON lability coincided with a large proportion of DCAA, relative to TDN, or a high algal biomass. The L/D ratio of especially dissolved combined glutamic acid appeared to be a potential indicator of DON lability. DCAA, as well as dissolved free amino acids (DFAA), were dominant nutrient sources to the bacteria, on average sustaining 77% (range 8 to 136%) of the bacterial N demand. In addition to amino acids, the bacteria incorporated or released DIN and urea. The effect of solar radiation on DON biolability was tested, but no consistent evidence for a light effect on transformation or bacterial utilization of recalcitrant DON was found. Our results show that there is an active microbial cycling of DON in the gulf, driven in part by input of N from the Daugava River. In summer, availability of assimilable N appears to limit the microbial activity as indicated by an estimated C/N ratio of 43 of labile DOM, as compared to a ratio of 4 in May. The microbial N dynamics in the Gulf of Riga are comparable to low-eutrophic estuaries and do not indicate direct eutrophication effects.
Animals studies have demonstrated that in addition to inhibiting growth hormone (GH) secretion octreotide inhibits in a direct manner hepatic or peripheral insulin-like growth factor I (IGF-I) ...generation. To test this hypothesis in humans we studied ten GH-deficient patients with frequent blood sampling during 38 h on two occasions. Regular GH therapy was discontinued 72 h prior to each study period. At the start of each study a subcutaneous (sc) injection of GH (3 IU/m2) was given (at 18.00 h). In a single-blinded crossover design, patients received a continuous sc infusion of either octreotide (200 micrograms/24 h) or placebo (saline). The pharmacokinetics of GH were similar on the two occasions. The area under the curve +/- SEM of serum GH was 142.5 +/- 53.6 micrograms.l-1 x h-1 (octreotide) and 144.8 +/- 41.8 micrograms.l-1 x h-1 (placebo), (p = 0.73); Cmax (microgram/l) was 12.5 +/- 1.47 (octreotide) and 12.8 +/- 1.42 (placebo) (p = 0.83), and Tmax (h) was 6.1 +/- 0.97 (octreotide) and 5.2 +/- 0.65 (placebo) (p = 0.49). Growth hormone administration was associated with an increase in serum IGF-I (microgram/l), which was identical during the two studies, from 85.3 +/- 19.4 to 174.25 +/- 30.3 for octreotide and from 97.0 +/- 26.4 to 158.8 +/- 28.2 for placebo. Mean IGF-I levels (microgram/l) were 138.2 +/- 25.1 (octreotide) and 134.5 +/- 28.6 (placebo) (p = 0.78). Similarly, the increase in IGF binding protein 3 (IGFBP-3) levels was identical. Mean IGFBP-3 levels (microgram/l) were 2303 +/- 323 (octreotide) and 2200 +/- 361 (placebo) (p = 0.25).
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