Performance of care for end‐of‐life cancer patients in Tuscany: The interplay between place of care, aggressive treatments, opioids, and place of death. A retrospective cohort study

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The seaweeds Fucus vesiculosus and Ascophyllum nodosum are significant contributors to coastal iodine emissions

Based on the results of a pilot study in 2007, which found high mixing ratios of molecular iodine (I2) above the intertidal macroalgae (seaweed) beds at Mweenish Bay (Ireland), we extended the study to nine different locations in the vicinity of Mace Head Atmospheric Research Station on the west coast of Ireland during a field campaign in 2009. The mean values of \chem{I_2} mixing ratio found above the macroalgae beds at nine different locations ranged from 104 to 393 ppt, implying a high source strength of I2. Such mixing ratios are sufficient to result in photochemically driven coastal new-particle formation events. Mixing ratios above the Ascophyllum nodosum and Fucus vesiculosus beds increased with exposure time: after 6 h exposure to ambient air the mixing ratios were one order of magnitude higher than those initially present. This contrasts with the emission characteristics of Laminaria digitata, where most I2 was emitted within the first half hour of exposure. Discrete in situ measurements (offline) of I2 emission from ambient air-exposed chamber experiments of L. digitata, A. nodosum and F. vesiculosus substantially supported the field observations. Further online and time-resolved measurements of the I2 emission from O3-exposed macroalgal experiments in a chamber confirmed the distinct I2 emission characteristics of A. nodosum and F. vesiculosus compared to those of L. digitata. The emission rates of A. nodosum and F. vesiculosus were comparable to or even higher than L. digitata after the initial exposure period of ~20–30 min. We suggest that A. nodosum and F. vesiculosus may provide an important source of photolabile iodine in the coastal boundary layer and that their impact on photochemistry and coastal new-particle formation should be reevaluated in light of their longer exposure at low tide and their widespread distribution

Spitzer IRS Spectral Mapping of the Toomre Sequence: Spatial Variations of PAH, Gas, and Dust Properties in Nearby Major Mergers

We have mapped the key mid-IR diagnostics in eight major merger systems of the Toomre Sequence (NGC4676, NGC7592, NGC6621, NGC2623, NGC6240, NGC520, NGC3921, and NGC7252) using the Spitzer Infrared Spectrograph (IRS). With these maps, we explore the variation of the ionized-gas, PAH, and warm-gas (H_2) properties across the sequence and within the galaxies. While the global PAH interband strength and ionized gas flux ratios ([Ne III]/[Ne II]) are similar to those of normal star forming galaxies, the distribution of the spatially resolved PAH and fine structure line flux ratios is significant different from one system to the other. Rather than a constant H_2/PAH flux ratio, we find that the relation between the H_2 and PAH fluxes is characterized by a power law with a roughly constant exponent (0.61+/-0.05) over all merger components and spatial scales. While following the same power law on local scales, three galaxies have a factor of ten larger integrated (i.e. global) H_2/PAH flux ratio than the rest of the sample, even larger than what it is in most nearby AGNs. These findings suggest a common dominant excitation mechanism for H_2 emission over a large range of global H_2/PAH flux ratios in major mergers. Early merger systems show a different distribution between the cold (CO J=1-0) and warm (H_2) molecular gas component, which is likely due to the merger interaction. Strong evidence for buried star formation in the overlap region of the merging galaxies is found in two merger systems (NGC6621 and NGC7592) as seen in the PAH, [Ne II], [Ne III], and warm gas line emission, but with no apparent corresponding CO (J=1-0) emission. Our findings also demonstrate that the variations of the physical conditions within a merger are much larger than any systematic trends along the Toomre Sequence.Comment: 35 pages, accepted for publication in ApJ

General practitioner workforce planning: assessment of four policy directions

<p>Abstract</p> <p>Background</p> <p>Estimating the supply of GPs into the future is important in forecasting shortages. The lengthy training process for medicine means that adjusting supply to meet demand in a timely fashion is problematic. This study uses Ireland as a case study to determine the future demand and supply of GPs and to assess the potential impact of several possible interventions to address future shortages.</p> <p>Methods</p> <p>Demand was estimated by applying GP visit rates by age and sex to national population projections. Supply was modelled using a range of parameters derived from two national surveys of GPs. A stochastic modelling approach was adopted to determine the probable future supply of GPs. Four policy interventions were tested: increasing vocational training places; recruiting GPs from abroad; incentivising later retirement; increasing nurse substitution to enable practice nurses to deliver more services.</p> <p>Results</p> <p>Relative to most other European countries, Ireland has few GPs per capita. Ireland has an ageing population and demand is estimated to increase by 19% by 2021. Without intervention, the supply of GPs will be 5.7% less than required in 2021. Increasing training places will enable supply to meet demand but only after 2019. Recruiting GPs from overseas will enable supply to meet demand continuously if the number recruited is approximately 0.8 per cent of the current workforce per annum. Later retirement has only a short-term impact. Nurse substitution can enable supply to meet demand but only if large numbers of practice nurses are recruited and allowed to deliver a wide range of GP services.</p> <p>Conclusions</p> <p>A significant shortfall in GP supply is predicted for Ireland unless recruitment is increased. The shortfall will have numerous knock-on effects including price increases, longer waiting lists and an increased burden on hospitals. Increasing training places will not provide an adequate response to future shortages. Foreign recruitment has ethical considerations but may provide a rapid and effective response. Increased nurse substitution appears to offer the best long-term prospects of addressing GP shortages and presents the opportunity to reshape general practice to meet the demands of the future.</p

Fermi Observations of the Very Hard Gamma-ray Blazar PG 1553+113

We report the observations of PG 1553+113 during the first ~200 days of Fermi Gamma-ray Space Telescope science operations, from 4 August 2008 to 22 February 2009 (MJD 54682.7-54884.2). This is the first detailed study of PG 1553+113 in the GeV gamma-ray regime and it allows us to fill a gap of three decades in energy in its spectral energy distribution. We find PG 1553+113 to be a steady source with a hard spectrum that is best fit by a simple power-law in the Fermi energy band. We combine the Fermi data with archival radio, optical, X-ray and very high energy (VHE) gamma-ray data to model its broadband spectral energy distribution and find that a simple, one-zone synchrotron self-Compton model provides a reasonable fit. PG 1553+113 has the softest VHE spectrum of all sources detected in that regime and, out of those with significant detections across the Fermi energy bandpass so far, the hardest spectrum in that energy regime. Thus, it has the largest spectral break of any gamma-ray source studied to date, which could be due to the absorption of the intrinsic gamma-ray spectrum by the extragalactic background light (EBL). Assuming this to be the case, we selected a model with a low level of EBL and used it to absorb the power-law spectrum from PG 1553+113 measured with Fermi (200 MeV - 157 GeV) to find the redshift which gave the best fit to the measured VHE data (90 GeV - 1.1 TeV) for this parameterisation of the EBL. We show that this redshift can be considered an upper limit on the distance to PG 1553+113.Comment: Accepted for publication in the Astrophysical Journal (28 pages, 5 figures

Unexpected consequences of increasing CO2 and ocean acidity on marine production of DMS and CH2ClI: Potential climate impacts

Increasing atmospheric mixing ratios of CO2 have already lowered surface ocean pH by 0.1 units compared to preindustrial values and pH is expected to decrease an additional 0.3 units by the end of this century. Pronounced physiological changes in some phytoplankton have been observed during previous CO2 perturbation experiments. Marine microorganisms are known to consume and produce climate-relevant organic gases. Concentrations of (CH3)2S (DMS) and CH2ClI were quantified during the Third Pelagic Ecosystem CO2 Enrichment Study. Positive feedbacks were observed between control mesocosms and those simulating future CO2. Dimethyl sulfide was 26% (±10%) greater than the controls in the 2x ambient CO2 treatments, and 18% (±10%) higher in the 3xCO2 mesocosms. For CH2ClI the 2xCO2 treatments were 46% (±4%) greater than the controls and the 3xCO2 mesocosms were 131% (±11%) higher. These processes may help contribute to the homeostasis of the planet

Online teacher development: collaborating in a virtual learning environment

Over recent years educational institutions have been making increasing use of virtual environments to set up collaborative activities for learners. While it is recognized that teachers play an important role in facilitating learner collaboration online they may not have the necessary skills to do so successfully. Thus, a small scale professional development programme was set up and piloted by two distance universities. The aims were to develop teachers’ experience of online group work; to trial a set of pilot activities which would raise awareness of factors contributing to successful collaborative online activity; and to identify professional development needs in this area. This article reports on the hands-on experience of a group of 20 teachers, examines some of the competences that are needed to successfully collaborate in virtual environments, and presents the skills that teachers need to foster online collaborative learning in the virtual classroom. Quantitative and qualitative data were collected, examining the levels of participation among participants, the collaborative activity of two groups, and teacher perception of the collaboration which took place. The skills identified include planning and managing the collaboration, designing appropriate activities, giving clear instructions and getting students to negotiate ground rules for participation, moderating at the right level, and choosing the right environment and the appropriate tool(s). While this study was carried out with language teachers, many of the findings are applicable to other subject areas where growing emphasis is placed on the development of collaborative skills

Palmitoylation and membrane cholesterol stabilize μ-opioid receptor homodimerization and G protein coupling

<p>Abstract</p> <p>Background</p> <p>A cholesterol-palmitoyl interaction has been reported to occur in the dimeric interface of the β₂-adrenergic receptor crystal structure. We sought to investigate whether a similar phenomenon could be observed with μ-opioid receptor (OPRM1), and if so, to assess the role of cholesterol in this class of G protein-coupled receptor (GPCR) signaling.</p> <p>Results</p> <p>C3.55(170) was determined to be the palmitoylation site of OPRM1. Mutation of this Cys to Ala did not affect the binding of agonists, but attenuated receptor signaling and decreased cholesterol associated with the receptor signaling complex. In addition, both attenuation of receptor palmitoylation (by mutation of C3.55[170] to Ala) and inhibition of cholesterol synthesis (by treating the cells with simvastatin, a HMG-CoA reductase inhibitor) impaired receptor signaling, possibly by decreasing receptor homodimerization and Gαi2 coupling; this was demonstrated by co-immunoprecipitation, immunofluorescence colocalization and fluorescence resonance energy transfer (FRET) analyses. A computational model of the OPRM1 homodimer structure indicated that a specific cholesterol-palmitoyl interaction can facilitate OPRM1 homodimerization at the TMH4-TMH4 interface.</p> <p>Conclusions</p> <p>We demonstrate that C3.55(170) is the palmitoylation site of OPRM1 and identify a cholesterol-palmitoyl interaction in the OPRM1 complex. Our findings suggest that this interaction contributes to OPRM1 signaling by facilitating receptor homodimerization and G protein coupling. This conclusion is supported by computational modeling of the OPRM1 homodimer.</p

Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS