A key challenge for numerical weather prediction
models is representing boundary layer clouds in cold air outbreaks (CAOs).
One important aspect is the evolution of microphysical properties as
...stratocumulus transitions to open cellular convection. Abel et al. (2017)
have shown, for the first time from in situ field observations, that the
break-up in CAOs over the eastern Atlantic may be controlled by the
development of precipitation in the cloud system while the boundary layer
becomes decoupled. This paper describes that case and examines in situ
measurements from three more CAOs. Flights were conducted using the UK
Facility for Airborne Atmospheric Measurements (FAAM) British Aerospace-146
(BAe-146) aircraft in the North Atlantic region around the UK, making
detailed microphysical measurements in the stratiform boundary layer. As the
cloudy boundary layer evolves prior to break-up, increasing liquid water
paths (LWPs) and drop sizes and the formation of liquid precipitation are
observed. Small numbers of ice particles, typically a few per litre, are also
observed. Eventually LWPs reduce significantly due to loss of water from the
stratocumulus cloud (SC) layer. In three of the cases, aerosols are removed
from the boundary layer across the transition. This process appears to be
similar to those observed in warm clouds and pockets of open cells (POCs) in
the subtropics. After break-up, deeper convective clouds form with bases warm
enough for secondary ice production (SIP), leading to rapid glaciation. It is
concluded that the precipitation is strongly associated with the break-up,
with both weakening of the capping inversion and boundary layer decoupling
also observed.
Abstract The GABAA receptor (GABAA R) α1 subunit mutation, A322D, causes autosomal dominant juvenile myoclonic epilepsy (JME). Previous in vitro studies demonstrated that A322D elicits α1(A322D) ...protein degradation and that the residual mutant protein causes a dominant-negative effect on wild type GABAA Rs. Here, we determined the effects of heterozygous A322D knockin (Hetα1 AD) and deletion (Hetα1 KO) on seizures, GABAA R expression, and motor cortex (M1) miniature inhibitory postsynaptic currents (mIPSCs) at two developmental time-points, P35 and P120. Both Hetα1 AD and Hetα1 KO mice experience absence seizures at P35 that persist at P120, but have substantially more frequent spontaneous and evoked polyspike wave discharges and myoclonic seizures at P120. Both mutant mice have increased total and synaptic α3 subunit expression at both time-points and decreased α1 subunit expression at P35, but not P120. There are proportional reductions in α3, β2, and γ2 subunit expression between P35 and P120 in wild type and mutant mice. In M1, mutants have decreased mIPSC peak amplitudes and prolonged decay constants compared with wild type, and the Hetα1 AD mice have reduced mIPSC frequency and smaller amplitudes than Hetα1 KO mice. Wild type and mutants exhibit proportional increases in mIPSC amplitudes between P35 and P120. We conclude that Hetα1 KO and Hetα1 AD mice model the JME subsyndrome, childhood absence epilepsy persisting and evolving into JME. Both mutants alter GABAA R composition and motor cortex physiology in a manner expected to increase neuronal synchrony and excitability to produce seizures. However, developmental changes in M1 GABAA Rs do not explain the worsened phenotype at P120 in mutant mice.
Bioaerosols pose risks to human health and agriculture and may influence the evolution of mixed-phase clouds and the hydrological cycle on local and regional scales. The availability and reliability ...of methods and data on the abundance and properties of atmospheric bioaerosols, however, are rather limited. Here we analyze and compare data from different real-time ultraviolet laser/light-induced fluorescence (UV-LIF) instruments with results from a culture-based spore sampler and offline molecular tracers for airborne fungal spores in a semi-arid forest in the southern Rocky Mountains of Colorado. Commercial UV-APS (ultraviolet aerodynamic particle sizer) and WIBS-3 (wideband integrated bioaerosol sensor, version 3) instruments with different excitation and emission wavelengths were utilized to measure fluorescent aerosol particles (FAPs) during both dry weather conditions and periods heavily influenced by rain. Seven molecular tracers of bioaerosols were quantified by analysis of total suspended particle (TSP) high-volume filter samples using a high-performance anion-exchange chromatography system with pulsed amperometric detection (HPAEC-PAD). From the same measurement campaign, Huffman et al. (2013) previously reported dramatic increases in total and fluorescent particle concentrations during and immediately after rainfall and also showed a strong relationship between the concentrations of FAPs and ice nuclei (Huffman et al., 2013; Prenni et al., 2013). Here we investigate molecular tracers and show that during rainy periods the atmospheric concentrations of arabitol (35.2 ± 10.5 ng m−3) and mannitol (44.9 ± 13.8 ng m−3) were 3–4 times higher than during dry periods. During and after rain, the correlations between FAP and tracer mass concentrations were also significantly improved. Fungal spore number concentrations on the order of 104 m−3, accounting for 2–5 % of TSP mass during dry periods and 17–23 % during rainy periods, were obtained from scaling the tracer measurements and from multiple analysis methods applied to the UV-LIF data. Endotoxin concentrations were also enhanced during rainy periods, but showed no correlation with FAP concentrations. Average mass concentrations of erythritol, levoglucosan, glucose, and (1 → 3)-β-D-glucan in TSP samples are reported separately for dry and rainy weather conditions. Overall, the results indicate that UV-LIF measurements can be used to infer fungal spore concentrations, but substantial development of instrumental and data analysis methods appears to be required for improved quantification.
Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients ...of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin cancer (excluding melanoma) for 481 patients during a median follow-up of 20.6 years. A total of 226 patients developed at least one cancer: 95 with non-skin cancer and 171 with skin cancer. In the intention-to-treat analysis, mean times to first non-skin cancer (16.0, 15.3, and 15.7 years for groups 1 through 3, respectively) and first skin cancer (13.6, 14.3, and 15.2 years, respectively) were not different among the three groups or between any subgroup. In multivariate analyses, non-skin cancer associated with increasing age and previous smoking history, whereas skin cancer associated with increasing age, nonbrown eye color, fairer skin, and a functioning transplant. Treatment allocation did not associate with development of either form of cancer in multivariate analyses. In conclusion, these immunosuppressive regimens, widely used in recent decades, carry similar risks for carcinogenicity after kidney transplantation.
Clinical trials are most informative for evidence-based decision making when they consistently measure and report outcomes of relevance to stakeholders. We aimed to assess the scope and consistency ...of outcomes reported in trials for hemodialysis.
Systematic review.
Adults requiring maintenance hemodialysis enrolled in clinical trials.
All Cochrane systematic reviews of interventions published by August 29, 2016, and the trials published and registered in ClinicalTrials.gov since January 2011.
Any hemodialysis-related interventions.
Frequency and characteristics of the reported outcome domains and measures.
From the 362 trials, we extracted and classified 10,713 outcome measures (a median of 21 IQR, 10-39 per trial) into 81 different outcome domains, of which 42 (52%) were surrogate; 25 (31%), clinical; and 14 (17%), patient reported. The number of outcome measures reported significantly changed over time. The 5 most commonly reported domains were all surrogates: phosphate (125 35% trials), dialysis adequacy (120 33%), anemia (115 32%), inflammatory markers (114 31%), and calcium (109 30%). Mortality, cardiovascular diseases, and quality of life were reported very infrequently (73 20%, 44 12%, and 32 9%, respectively).
For feasibility, we included a sampling frame that included only trials identified in Cochrane systematic reviews or ClinicalTrials.gov.
Outcomes reported in clinical trials involving adults receiving hemodialysis are focused on surrogate outcomes, rather than clinical and patient-centered outcomes. There is also extreme multiplicity and heterogeneity at every level: domain, measure, metric, and time point. Estimates of the comparative effectiveness of available interventions are unreliable and improvements over time have been inconsistent.
This article considers recent developments across the western world in the lethality of lone wolf terrorists during 2016 against the contextual framework of Rapoport’s theory regarding the existence ...of waves of terrorism, mirroring current extreme political and social situations. It highlights the similarities in terms of world conditions coupled to modus operandi that existed during the first wave of terrorism, the Anarchist wave, and currently, while highlighting recent increased lethality. The paper illustrates that current lone wolf behaviours, and the decreasing ‘Religiosity’ of fourth wave participants indicate that the wave’s breakwater may have been reached. A discussion of the role of mental health in influencing the behaviour of ‘lone wolf’ terrorists follows. It concludes that Islamic State’s current territorial losses, coupled to increased populism across the west may be potential areas where extreme social reactionary trends occur, that will ultimately manifest themselves as ‘Fifth Wave’ Terrorism; however cautions that any predictions in this regard are extremely difficult. It recommends that policy makers and law enforcement bodies closely monitor developments amongst those reacting to these significant geo political changes; and that there is an acknowledgement that mental health considerations must be included when discussing terrorist acts, and looking at mitigation measures.
The Amazon basin is a vast continental area in which atmospheric composition is relatively unaffected by anthropogenic aerosol particles. Understanding the properties of the natural biogenic aerosol ...particles over the Amazon rainforest is key to understanding their influence on regional and global climate. While there have been a number of studies during the wet season, and of biomass burning particles in the dry season, there has been relatively little work on the transition period – the start of the dry season in the absence of biomass burning. As part of the Brazil–UK Network for Investigation of Amazonian Atmospheric Composition and Impacts on Climate (BUNIAACIC) project, aerosol measurements, focussing on unpolluted biogenic air masses, were conducted at a remote rainforest site in the central Amazon during the transition from wet to dry season in July 2013. This period marks the start of the dry season but before significant biomass burning occurs in the region. Median particle number concentrations were 266 cm−3, with size distributions dominated by an accumulation mode of 130–150 nm. During periods of low particle counts, a smaller Aitken mode could also be seen around 80 nm. While the concentrations were similar in magnitude to those seen during the wet season, the size distributions suggest an enhancement in the accumulation mode compared to the wet season, but not yet to the extent seen later in the dry season, when significant biomass burning takes place. Submicron nonrefractory aerosol composition, as measured by an aerosol chemical speciation monitor (ACSM), was dominated by organic material (around 81 %). Aerosol hygroscopicity was probed using measurements from a hygroscopicity tandem differential mobility analyser (HTDMA), and a quasi-monodisperse cloud condensation nuclei counter (CCNc). The hygroscopicity parameter, κ, was found to be low, ranging from 0.12 for Aitken-mode particles to 0.18 for accumulation-mode particles. This was consistent with previous studies in the region, but lower than similar measurements conducted in Borneo, where κ ranged 0.17–0.37. A wide issue bioaerosol sensor (WIBS-3M) was deployed at ground level to probe the coarse mode, detecting primary biological aerosol by fluorescence (fluorescent biological aerosol particles, or FBAPs). The mean FBAP number concentration was 400 ± 242 L−1; however, this ranged from around 200 L−1 during the day to as much as 1200 L−1 at night. FBAPs dominated the coarse-mode particles, comprising between 55 and 75 % of particles during the day to more than 90 % at night. Non-FBAPs did not show a strong diurnal pattern. Comparison with previous FBAP measurements above canopy at the same location suggests there is a strong vertical gradient in FBAP concentrations through the canopy. Cluster analysis of the data suggests that FBAPs were dominated (around 70 %) by fungal spores. Further, long-term measurements will be required in order to fully examine the seasonal variability and distribution of primary biological aerosol particles through the canopy. This is the first time that such a suite of measurements has been deployed at this site to investigate the chemical composition and properties of the biogenic contributions to Amazonian aerosol during the transition period from the wet to the dry season, and thus provides a unique comparison to the aerosol properties observed during the wet season in previous similar campaigns. This was also the first deployment of a WIBS in the Amazon rainforest to study coarse-mode particles, particularly primary biological aerosol particles, which are likely to play an important role as ice nuclei in the region.
Catheter malfunction, including thrombosis, is associated with reduced dialysis adequacy, as well as an increased risk of catheter-related bacteraemia and mortality. The role of anticoagulants in the ...prevention of catheter malfunction remains uncertain.
This review aimed to compare the prophylactic effect of different anticoagulant agents, preparations, doses and administration on the incidence of central venous haemodialysis catheter-related malfunction and sepsis in patients with end-stage kidney disease (ESKD).
We searched the Cochrane Renal Group's Specialised Register to 7 January 2016 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
We included all randomised controlled trials (RCT) assessing anticoagulants compared with conventional care for the prevention of catheter malfunction in adult patients receiving haemodialysis for ESKD.
The primary outcome was catheter malfunction defined as a catheter blood flow of 200 mL/min or less, or as defined by study authors. Secondary outcomes were catheter-related bacteraemia, all-cause mortality and bleeding events. Relative risks (RR) with 95% confidence intervals (CI) for individual studies were pooled using random effects models within treatment classes. Analyses were conducted by class, with subgroup analyses performed of individual agents within classes.
We included 27 studies (3003 participants) that were followed up for a median of six months. Study interventions included alternative anticoagulant locking solutions (19 studies, 2216 patients), systemic agents (6 studies, 664 patients) and low or no dose heparin (2 studies, 123 patients). The most common comparison treatment was a locking solution of heparin 5000 IU/mL, used in 17 studies. No significant effect on catheter malfunction was observed for alternative anticoagulant locking solutions (RR 0.96, 95% CI 0.74 to 1.26), systemic agents (RR 0.59, 95% CI 0.28 to 1.23), or low or no dose heparin (RR 0.90, 95% CI 0.10 to 8.31). A significant reduction on incidence of catheter-related bacteraemia was observed for alternative anticoagulant locking solutions (RR 0.46, 95% CI 0.32 to 0.66) but not systemic agents (RR 2.41, 95% CI 0.89 to 6.55), and could not be assessed in reports of low or no dose heparin studies. No significant effect on all-cause mortality was observed for alternative anticoagulant locking solutions (RR 0.88, 95% CI 0.54 to 1.43) or systemic agents (RR 0.78, 95% CI 0.37 to 1.65), and was not reported in studies of low or no dose heparin. Bleeding events were only reported in eight studies, including only 2/5 studies of systemic warfarin, with no clear effect demonstrated (RR 1.43, 95% CI 0.86 to 2.39). For individual agents, recombinant tissue plasminogen (rt-PA) was the only locking solution shown to reduce catheter malfunction (RR 0.58, 95% CI 0.37 to 0.91) based on the results of a single study. No significant on catheter malfunction was observed for other individual classes of alternative anticoagulant locking solutions (citrate: RR 1.14, 95% CI 0.76 to 1.69; antibiotic: RR 1.48, 95% CI 0.79 to 2.77; ethanol: RR 0.88, 95% CI 0.21 to 3.67). On the other hand, all individual classes of alternative anticoagulant locking solutions, except ethanol, reduced catheter-related bacteraemia (citrate: RR 0.49, 95% CI 0.36 to 0.68; antibiotic: RR 0.27, 95% CI 0.11 to 0.70; rt-PA: RR 0.35, 95% CI 0.13 to 0.93; ethanol: RR 0.33, 95% CI 0.03 to 4.05). No significant effect on all-cause mortality was observed for any individual agent within the class of alternative locking solutions. Studies were mainly of low quality and underpowered with an average participant number of 75 and study duration of six months. The interpretation of the study evidence was further limited by the variation in tested interventions and outcome reporting.
The relative net benefit of anticoagulant therapies for prevention of catheter malfunction remains uncertain. Multiple agents appear to reduce catheter-related bacteraemia although the lack of clear assessment of harms and the limitations of study quality mean these results should be interpreted with caution. Methodological approaches can be used to avoid methods of reporting unduly affecting on the results of meta-analyses incorporating studies employed mixed reporting methods. Further high quality randomised studies, including safety outcomes, are needed.
Primary biological aerosol particles (PBAPs) are an abundant subset of atmospheric aerosol particles which comprise viruses, bacteria, fungal spores, pollen, and fragments such as plant and animal ...debris. The abundance and diversity of these particles remain poorly constrained, causing significant uncertainties for modelling scenarios and for understanding the potential implications of these particles in different environments. PBAP concentrations were studied at four different sites in the United Kingdom (Weybourne, Davidstow, Capel Dewi, and Chilbolton) using an ultraviolet light-induced fluorescence (UV-LIF) instrument, the Wideband Integrated Bioaerosol Spectrometer (WIBS), versions 3 and 4.Using hierarchical agglomerative cluster (HAC) analysis, particles were statistically discriminated. Fluorescent particles and clusters were then analysed by comparing to laboratory data of known particle types, assessing their diurnal variation and examining their relationship to the meteorological variables temperature, relative humidity, wind speed, and wind direction. Using local land cover types, sources of the suspected fluorescent particles and clusters were then identified.Most sites exhibited a wet discharged fungal spore dominance, with the exception of one site, Davidstow, which had higher concentrations of bacteria, suggested to result from the presence of a local dairy factory and farm. Differences were identified as to the sources of wet discharged fungal spores, with particles originating from arable and horticultural land at Chilbolton, and improved grassland areas at Weybourne. Total fluorescent particles at Capel Dewi were inferred to comprise two sources, with bacteria originating from the broadleaf and coniferous woodland and wet discharged fungal spores from nearby improved grassland areas, similar to Weybourne.The use of the HAC method and a higher fluorescence threshold (9 standard deviations instead of 3) produced clusters which were considered to be biological following the complete analysis. More published data and information on the reaction of different speciated biological particle types to fluctuations in meteorological conditions, such as relative humidity and temperature, would aid particle type characterisation in studies such as this.
We demonstrate, for the first time, continuous real-time observations of airborne bio-fluorescent aerosols recorded at the British Antarctic Survey's Halley VI Research Station, located on the Brunt ...Ice Shelf close to the Weddell Sea coast (lat 75°34′59′′ S, long 26°10′0′′ W) during Antarctic summer, 2015. As part of the NERC MAC (Microphysics of Antarctic Clouds) aircraft aerosol cloud interaction project, observations with a real-time ultraviolet-light-induced fluorescence (UV-LIF) spectrometer were conducted to quantify airborne biological containing particle concentrations along with dust particles as a function of wind speed and direction over a 3-week period. Significant, intermittent enhancements of both non- and bio-fluorescent particles were observed to varying degrees in very specific wind directions and during strong wind events. Analysis of the particle UV-induced emission spectra, particle sizes and shapes recorded during these events suggest the majority of particles were likely a subset of dust with weak fluorescence emission responses. A minor fraction, however, were likely primary biological particles that were very strongly fluorescent, with a subset identified as likely being pollen based on comparison with laboratory data obtained using the same instrument. A strong correlation of bio-fluorescent particles with wind speed was observed in some, but not all, periods. Interestingly, the fraction of fluorescent particles to total particle concentration also increased significantly with wind speed during these events. The enhancement in concentrations of these particles could be interpreted as due to resuspension from the local ice surface but more likely due to emissions from distal sources within Antarctica as well as intercontinental transport. Likely distal sources identified by back trajectory analyses and dispersion modelling were the coastal ice margin zones in Halley Bay consisting of bird colonies with likely associated high bacterial activity together with contributions from exposed ice margin bacterial colonies but also long-range transport from the southern coasts of Argentina and Chile. Dispersion modelling also demonstrated emissions from shipping lanes, and therefore marine anthropogenic sources cannot be ruled out. Average total concentrations of total fluorescent aerosols were found to be 1.9 ± 2.6 L−1 over a 3-week period crossing over from November into December, but peak concentrations during intermittent enhancement events could be up to several tens per litre. While this short pilot study is not intended to be generally representative of Antarctic aerosol, it demonstrates the usefulness of the UV-LIF measurement technique for quantification of airborne bioaerosol concentrations and to understand their dispersion. The potential importance for microbial colonisation of Antarctica is highlighted.
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