Adolescent seasonal allergic rhinitis and the impact of health-care professional training:cluster randomised controlled trial of a complex intervention in primary care

BACKGROUND: Seasonal allergic rhinitis is typically poorly managed, particularly in adolescents, in whom it is responsible for considerable morbidity. Our previous work has demonstrated that if poorly controlled this can impair educational performance. AIM: The primary aim of this trial was to assess the impact of a primary care-based professional training intervention on clinical outcomes in adolescents with seasonal allergic rhinitis. METHODS: Cluster trial in which UK general practice staff were randomised to a short, intensive workshop on the evidence-based management of seasonal allergic rhinitis. The primary outcome measure was the change in the validated Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities (RQLQ(S)) score between baseline and 6 weeks post intervention (minimal clinically important difference=0.5). Secondary outcome measures of interest included health-care professionals' knowledge and confidence in managing seasonal allergic rhinitis, number of seasonal allergic rhinitis-related consultations, relevant treatments prescribed and symptom scores. RESULTS: Thirty-eight general practices were randomised (20 in the intervention arm) and 246 patients (50.2% males, mean age 15 years) were included in the primary outcome analysis. Health-care professionals' knowledge and confidence of the clinical management of seasonal allergic rhinitis improved. This did not, however, result in clinically or statistically significant improvements in RQLQ(S): -0.15, (95% confidence interval, -0.5 to +0.2). There were no differences in consultation frequency, treatments issued for seasonal allergic rhinitis or symptom scores. CONCLUSIONS: Although associated with increases in professionals' self-assessed confidence and understanding of seasonal allergic rhinitis management, this intensive training workshop did not translate into improvements in adolescents' disease-specific quality of life or a reduction in rhinitis symptoms

The optical/NIR afterglow of GRB 111209A: Complex yet not unprecedented

Context. Afterglows of gamma-ray bursts (GRBs) are simple in the most basic model, but can show many complex features. The ultra-long duration GRB 111209A, one of the longest GRBs ever detected, also has the best-monitored afterglow in this rare class of GRBs. Aims. We want to address the question whether GRB 111209A was a special event beyond its extreme duration alone, and whether it is a classical GRB or another kind of high-energy transient. The afterglow may yield significant clues. Methods. We present afterglow photometry obtained in seven bands with the GROND imager as well as in further seven bands with the Ultraviolet/Optical Telescope (UVOT) on-board the Neil Gehrels Swift Observatory. The light curve is analysed by multi-band modelling and joint fitting with power-laws and broken power-laws, and we use the contemporaneous GROND data to study the evolution of the spectral energy distribution. We compare the optical afterglow to a large ensemble we have analysed in earlier works, and especially to that of another ultra-long event, GRB 130925A. We furthermore undertake a photometric study of the host galaxy. Results. We find a strong, chromatic rebrightening event at ≈0.8 days after the GRB, during which the spectral slope becomes redder. After this, the light curve decays achromatically, with evidence for a break at about 9 days after the trigger. The afterglow luminosity is found to not be exceptional. We find that a double-jet model is able to explain the chromatic rebrightening. The afterglow features have been detected in other events and are not unique. Conclusions. The duration aside, the GRB prompt emission and afterglow parameters of GRB 111209A are in agreement with the known distributions for these parameters. While the central engine of this event may differ from that of classical GRBs, there are multiple lines of evidence pointing to GRB 111209A resulting from the core-collapse of a massive star with a stripped envelope

Ca2+-induced changes in energy metabolism and viability of melanoma cells

Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. We show here that a rise in intracellular-free calcium ion (Ca2+), induced by Ca2+-ionophore A23187, exerted a deleterious effect on glycolysis and viability of B16 melanoma cells. Ca2+-ionophore caused a dose-dependent detachment of phosphofructokinase (EC 2.7.1.11), one of the key enzymes of glycolysis, from cytoskeleton. It also induced a decrease in the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis. All these changes occurred at lower concentrations of the drug than those required to induce a reduction in viability of melanoma cells. We also found that low concentrations of Ca2+-ionophore induced an increase in adenosine 5′-triphosphate (ATP), which most probably resulted from the increase in mitochondrial-bound hexokinase, which reflects a defence mechanism. This mechanism can no longer operate at high concentrations of the Ca2+-ionophore, which causes a decrease in mitochondrial and cytosolic hexokinase, leading to a drastic fall in ATP and melanoma cell death. The present results suggest that drugs which are capable of inducing accumulation of intracellular-free Ca2+ in melanoma cells would cause a reduction in energy-producing systems, leading to melanoma cell death. © 1999 Cancer Research Campaig

Do differences in understory light contribute to species distributions along a tropical rainfall gradient?

In tropical forests, regional differences in annual rainfall correlate with differences in plant species composition. Although water availability is clearly one factor determining species distribution, other environmental variables that covary with rainfall may contribute to distributions. One such variable is light availability in the understory, which decreases towards wetter forests due to differences in canopy density and phenology. We established common garden experiments in three sites along a rainfall gradient across the Isthmus of Panama in order to measure the differences in understory light availability, and to evaluate their influence on the performance of 24 shade-tolerant species with contrasting distributions. Within sites, the effect of understory light availability on species performance depended strongly on water availability. When water was not limiting, either naturally in the wetter site or through water supplementation in drier sites, seedling performance improved at higher light. In contrast, when water was limiting at the drier sites, seedling performance was reduced at higher light, presumably due to an increase in water stress that affected mostly wet-distribution species. Although wetter forest understories were on average darker, wet-distribution species were not more shade-tolerant than dry-distribution species. Instead, wet-distribution species had higher absolute growth rates and, when water was not limiting, were better able to take advantage of small increases in light than dry-distribution species. Our results suggest that in wet forests the ability to grow fast during temporary increases in light may be a key trait for successful recruitment. The slower growth rates of the dry-distribution species, possibly due to trade-offs associated with greater drought tolerance, may exclude these species from wetter forests

Hyper-IgG4 disease: report and characterisation of a new disease

BACKGROUND: We highlight a chronic inflammatory disease we call 'hyper-IgG4 disease', which has many synonyms depending on the organ involved, the country of origin and the year of the report. It is characterized histologically by a lymphoplasmacytic inflammation with IgG4-positive cells and exuberant fibrosis, which leaves dense fibrosis on resolution. A typical example is idiopathic retroperitoneal fibrosis, but the initial report in 2001 was of sclerosing pancreatitis. METHODS: We report an index case with fever and severe systemic disease. We have also reviewed the histology of 11 further patients with idiopathic retroperitoneal fibrosis for evidence of IgG4-expressing plasma cells, and examined a wide range of other inflammatory conditions and fibrotic diseases as organ-specific controls. We have reviewed the published literature for disease associations with idiopathic, systemic fibrosing conditions and the synonyms: pseudotumour, myofibroblastic tumour, plasma cell granuloma, systemic fibrosis, xanthofibrogranulomatosis, and multifocal fibrosclerosis. RESULTS: Histology from all 12 patients showed, to varying degrees, fibrosis, intense inflammatory cell infiltration with lymphocytes, plasma cells, scattered neutrophils, and sometimes eosinophilic aggregates, with venulitis and obliterative arteritis. The majority of lymphocytes were T cells that expressed CD8 and CD4, with scattered B-cell-rich small lymphoid follicles. In all cases, there was a significant increase in IgG4-positive plasma cells compared with controls. In two cases, biopsies before and after steroid treatment were available, and only scattered plasma cells were seen after treatment, none of them expressing IgG4. Review of the literature shows that although pathology commonly appears confined to one organ, patients can have systemic symptoms and fever. In the active period, there is an acute phase response with a high serum concentration of IgG, and during this phase, there is a rapid clinical response to glucocorticoid steroid treatment. CONCLUSION: We believe that hyper-IgG4 disease is an important condition to recognise, as the diagnosis can be readily verified and the outcome with treatment is very good

An approach to developing a prediction model of fertility intent among HIV-positive women and men in Cape Town, South Africa: a case study

As a ‘case-study’ to demonstrate an approach to establishing a fertility-intent prediction model, we used data collected from recently diagnosed HIV-positive women (N = 69) and men (N = 55) who reported inconsistent condom use and were enrolled in a sexual and reproductive health intervention in public sector HIV care clinics in Cape Town, South Africa. Three theoretically-driven prediction models showed reasonable sensitivity (0.70–1.00), specificity (0.66–0.94), and area under the receiver operating characteristic curve (0.79–0.89) for predicting fertility intent at the 6-month visit. A k-fold cross-validation approach was employed to reduce bias due to over-fitting of data in estimating sensitivity, specificity, and area under the curve. We discuss how the methods presented might be used in future studies to develop a clinical screening tool to identify HIV-positive individuals likely to have future fertility intent and who could therefore benefit from sexual and reproductive health counselling around fertility options

A real-time fast radio burst: Polarization detection and multiwavelength follow-up

Fast radio bursts (FRBs) are one of the most tantalizing mysteries of the radio sky; their progenitors and origins remain unknown and until now no rapid multiwavelength follow-up of an FRB has been possible. New instrumentation has decreased the time between observation and discovery from years to seconds, and enables polarimetry to be performed on FRBs for the first time. We have discovered an FRB (FRB 140514) in real-time on 2014 May 14 at 17:14:11.06 UTC at the Parkes radio telescope and triggered follow-up at other wavelengths within hours of the event. FRB 140514 was found with a dispersion measure (DM) of 562.7(6) cm-3 pc, giving an upper limit on source redshift of z ≲ 0.5. FRB 140514 was found to be 21 ± 7 per cent (3σ) circularly polarized on the leading edge with a 1σ upper limit on linear polarization <10 per cent. We conclude that this polarization is intrinsic to the FRB. If there was any intrinsic linear polarization, as might be expected from coherent emission, then it may have been depolarized by Faraday rotation caused by passing through strong magnetic fields and/or high-density environments. FRB 140514 was discovered during a campaign to re-observe known FRB fields, and lies close to a previous discovery, FRB 110220; based on the difference in DMs of these bursts and time-on-sky arguments, we attribute the proximity to sampling bias and conclude that they are distinct objects. Follow-up conducted by 12 telescopes observing from X-ray to radio wavelengths was unable to identify a variable multiwavelength counterpart, allowing us to rule out models in which FRBs originate from nearby (z < 0.3) supernovae and long duration gamma-ray bursts. © 2014 The Authors

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio