Increases in Future AR Count and Size: Overview of the ARTMIP Tier 2 CMIP5/6 Experiment.

The Atmospheric River (AR) Tracking Method Intercomparison Project (ARTMIP) is a community effort to systematically assess how the uncertainties from AR detectors (ARDTs) impact our scientific understanding of ARs. This study describes the ARTMIP Tier 2 experimental design and initial results using the Coupled Model Intercomparison Project (CMIP) Phases 5 and 6 multi-model ensembles. We show that AR statistics from a given ARDT in CMIP5/6 historical simulations compare remarkably well with the MERRA-2 reanalysis. In CMIP5/6 future simulations, most ARDTs project a global increase in AR frequency, counts, and sizes, especially along the western coastlines of the Pacific and Atlantic oceans. We find that the choice of ARDT is the dominant contributor to the uncertainty in projected AR frequency when compared with model choice. These results imply that new projects investigating future changes in ARs should explicitly consider ARDT uncertainty as a core part of the experimental design.

Forecasted attribution of the human influence on Hurricane Florence.

Changes in extreme weather, such as tropical cyclones, are one of the most serious ways society experiences the impact of climate change. Advance forecasted conditional attribution statements, using a numerical model, were made about the anthropogenic climate change influence on an individual tropical cyclone, Hurricane Florence. Mean total overland rainfall amounts associated with the forecasted storm's core were increased by 4.9 ± 4.6% with local maximum amounts experiencing increases of 3.8 ± 5.7% due to climate change. A slight increase in the forecasted storm size of 1 to 2% was also attributed. This work reviews our forecasted attribution statement with the benefit of hindsight, demonstrating credibility of advance attribution statements for tropical cyclones.

A multiyear cross-sectional study of U.S. national prescribing patterns of first-generation sedating antihistamines in older adults with skin disease.

BACKGROUND: First-generation antihistamines (FGAs) are classified as 'potentially inappropriate' for use in older patients (patients aged ≥ 65 years). However, the prevalence of and factors associated with FGA prescription have not been studied. OBJECTIVES: To examine FGA prescription rates for older patients who visited dermatology offices, and compare them to those for younger patients (patients aged 18-65 years) who visited dermatology offices and those for older patients who visited primary-care physicians (PCPs). METHODS: This was a multiyear cross-sectional observational study using data from the U.S. National Ambulatory Medical Care Survey (2006-2015). Visits by patients aged 18 years or older were included in the study; the data comprised 15 243 dermatology office visits and 66 036 PCP office visits. The main outcome was FGA prescription. Other variables included physician specialty (dermatologist or PCP), patient's age, diagnosis of dermatological conditions and reason for visit. RESULTS: For dermatology visits, the overall FGA prescription rate for older patients was similar to that for younger patients (1·5% vs. 1·2%; P = 0·19), even when the diagnosis was dermatitis or pruritus (3·7% vs. 4·8%; P = 0·21) or when itch was a complaint (7·6% vs. 6·7%; P = 0·64). However, the rate of FGA prescription for dermatology visits was lower than that for PCP visits, in analyses matched for patient and visit characteristics (3·9% vs. 7·4%; P = 0·02). CONCLUSIONS: Our findings suggest that FGAs are overprescribed to older patients but that dermatologists are less likely to prescribe FGAs than PCPs. What's already known about this topic? First-generation antihistamines (FGAs) have been shown to pose substantial risks to older adults, including cognitive impairment, falls, confusion, dry mouth and constipation. Therefore, FGAs have been classified as 'potentially inappropriate' for use in older patients by the American Geriatrics Society. It has also been shown that dermatologists do not always take patient characteristics (e.g. age or life expectancy) into account when deciding on a treatment, instead following a 'one-size-fits-all' approach. What does this study add? FGAs are often prescribed during dermatology visits, and prescription rates do not differ between older and younger patients. There were no significant differences in prescription rates when comparing younger and older adults with the same diagnosis or symptom (e.g. dermatitis, pruritus or itch). FGAs are prescribed at higher rates in primary-care offices than in dermatology offices.

Comparing the efficacy of field treatments for actinic keratosis: a critical appraisal of a randomized trial in the New England Journal of Medicine.

AIM: Jansen et al. conducted a randomized trial to compare the efficacy of four field treatments for actinic keratosis (AK). SETTING AND DESIGN: This was a multicentre, single-blind, randomized trial conducted in the dermatology departments of four Netherlands hospitals. Patients were not blinded. The investigator who evaluated the trial outcome was blinded. STUDY EXPOSURE: This study included adult patients with at least five AKs on the face or vertex scalp. Patients were randomized to treatment with fluorouracil 5% cream, imiquimod 5% cream, methyl aminolaevulinate photodynamic therapy (MAL-PDT) or ingenol mebutate 0·015% gel. OUTCOMES: The primary outcome was whether patients had ≥ 75% reduction in AK count 12 months after treatment. RESULTS: In total 624 patients participated. The likelihood of having ≥ 75% reduction in AK count 12 months after treatment was significantly higher (twice as high or greater) for fluorouracil than for any other therapy. Approximately 75% of patients treated with fluorouracil experienced ≥ 75% reduction in AK count at 12 months. CONCLUSIONS: Jansen et al. conclude that 1 year after treatment, fluorouracil was significantly more effective at AK reduction than imiquimod, MAL-PDT or ingenol mebutate.

Determination of the thermal properties of leaves by non-invasive contact­free laser probing.

The thermal properties of materials provide valuable data for quality monitoring and the rational design of process steps where heating is required. Here we report a rapid, simple and reliable technique that determines the most important thermal properties of leaves, i.e. the specific heat capacity (cp) and thermal conductivity (λ). Such data are useful when leaves are heated during processing, e.g. for the precipitation of host cell proteins during the extraction of high-value products such as recombinant proteins produced by molecular farming. The cp of tobacco (Nicotiana tabacum) and Nicotiana benthamiana leaves was determined by infrared measurement of the temperature increase caused by a near-infrared laser pulse of defined length and intensity. We used the sample temperature profiles to calculate λ based on exponential fits of the temperature decline, taking convective heat transfer and thermal radiation into account. We found that the average cp was 3661 ± 323 J kg(-1) K(-1) (n=19) for tobacco and 2253 ± 285 J kg(-1) K(-1) (n=25) for N. benthamiana, whereas the average λ was 0.49 ± 0.13 (n=19) for tobacco and 0.41 ± 0.20 (n=25) Jm(-1) s(-1)K(-1) for N. benthamiana. These values are similar to those established for other plant species by photothermal imaging and other methods. The cp and λ values of leaves can be determined easily using our non-invasive method, which is therefore suitable for the in-line or at-line monitoring of plants, e.g. during the highly regulated production of biopharmaceutical proteins.

[Myosin storage myopathy: a rare subtype of protein aggregate myopathies]. / Myosinspeichermyopathie: eine seltene Unterform der Proteinaggregationsmyopathien.

Myopathies with pathological protein aggregates comprise a numerically significant group of sporadic and hereditary muscle disorders. A rare disease entity within the group of protein aggregate myopathies is the myosin storage myopathy, which is caused by heterozygous mutations in the MYH7 gene which encodes the slow/beta-myosin heavy chain. We report the clinical, myopathological and MRI findings in the first German patient suffering from a myosin storage myopathy due to a heterozygous R 1845W missense mutation.

[Surveillance following anesthesia procedures : Comments on the new recommendations of the German Society for Anesthesiology and Intensive Care medicine and the Professional Association of German Anesthetists]. / Uberwachung nach Anästhesieverfahren : Kommentar zu den neuen Empfehlung der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und des Berufsverbandes Deutscher Anästhesisten.

Allowances have been made for surveillance as an essential component in the chain of anesthesiological care and the increasing importance of the recovery room by reformulation of the recommendations of the German Society for Anesthesiology and Intensive Care medicine (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin, DGAI) and the Professional Association of German Anesthetists (Berufsverband Deutscher Anästhesisten, BDA) on surveillance following anesthesia procedures. These recommendations replace the previous guidelines on postoperative surveillance and the recommendations on organization and equipping of recovery units. In the following article the essential new aspects of the recommendations on surveillance following anesthesia procedures will be presented.

Pharmacokinetics and clinical toxicity of prilocaine and ropivacaine following combined drug administration in brachial plexus anesthesia.

OBJECTIVE: Local anesthetics (LA) are often administered in combination for regional anesthesia in order to obtain the specific advantages (onset and duration of effect) of each drug. However, few data on the safety of such combinations are available and consequently plasma concentrations possibly associated with toxicity and interactions between the specific anesthetics are not sufficiently established. We measured pharmacokinetics and toxicity parameters of prilocaine and ropivacaine after combined use as single doses in brachial plexus blockade. METHODS: In an open clinical study using a combined dose regime (300 mg prilocaine followed immediately by 75 mg ropivacaine) total plasma concentrations of prilocaine and ropivacaine were measured serially in 60 patients using a gas-chromatographic method. The data were analyzed regarding a relationship with central nervous and cardiovascular toxicity. RESULTS: Following the administration in combination prilocaine and ropivacaine were rapidly absorbed. Mean prilocaine peak plasma concentrations (mean Cmax = 1.51 microg/ml) were measured between 15 and 30 min after injection. Highest ropivacaine plasma concentrations (mean Cmax = 1.12 microg/ml) were seen between 30 min and 1 hour after injection (calculated mean tmax = 44 min). One of 59 patients showed signs of myoclonus which were suspected of being due to intravascular injection. There was no relevant cardiovascular toxicity observed in terms of changes in the QRS complex, PQ interval prolongation, AV dissociation, occurrence of extrasystoles or sinus arrest. The pharmacokinetics of combined administration did not differ from those of prilocaine and ropivacaine given alone. CONCLUSION: The use of a combined prilocaine/ ropivacaine (300 mg/75 mg) dose regimen in patients given single dose for brachial plexus blockade can generally be regarded as safe with regard to peak plasma concentrations and cardiovascular toxicity and this holds true for patients with a higher perioperative risk profile (ASA III grading, American Society of Anesthesiologists). The considerable inter-individual variation in LA peak plasma concentrations observed in our patients and the one case of suspected accidental intravascular injection, highlight the necessity of adequate monitoring of the patients undergoing LA injections.

Mild clinical and histopathological features in patients who carry the frequent and causative malignant hyperthermia RyR1 mutation p.Thr2206Met.

OBJECTIVE: Malignant hyperthermia (MH) is a classically unapparent pharmacogenetic disorder of the skeletal muscles triggered by inhalational anesthetics or depolarizing muscle relaxants. The disposition to MH is inherited in an autosomal-dominant manner and is primarily due to mutations in the gene for the ryanodine receptor type 1 (RyR1). The present study intended to analyze whether mild muscular symptoms (elevation of the resting CK, cramps in the calves, slight calf hypertrophy) may be associated with susceptibility to MH and/or with histopathological changes. METHODS: A muscle biopsy was taken from 12 out of 44 blood relatives (three generations) of a large family and was investigated with the halothane/caffeine in vitro contracture test (IVCT). Afterwards a histological, histochemical and immunhistological examination was performed. Altogether in 29 persons the DNA was analyzed for mutations in the RyR1-gene. RESULTS: Eight persons were diagnosed as susceptible to MH (MHS) by the IVCT, 4 were MH negative. All MHS persons carried the MH causative c.6617C > T (Thr2206Met) mutation and showed slight clinical signs of a myopathy as well as mild biopsy changes with isolated hypotrophic fibers and disseminated small areas with reduction of oxidative staining (multi-minicore like lesions). The Thr2206Met mutation was identified in another further 9 relatives who also experienced mild myopathological features. Clinical MH incidents were not reported in this large family. CONCLUSION: The RyR1 Thr2206Met mutation is one of the most frequent mutations in the European MH population but carriers are normally healthy. In this study we could demonstrate that the MH causative Thr2206Met mutation may also be associated both with clinical symptoms of a mild myopathy and histopathological changes in the oxidative inter myofibrillar network.

Incorporating model quality information in climate change detection and attribution studies.

In a recent multimodel detection and attribution (D&A) study using the pooled results from 22 different climate models, the simulated "fingerprint" pattern of anthropogenically caused changes in water vapor was identifiable with high statistical confidence in satellite data. Each model received equal weight in the D&A analysis, despite large differences in the skill with which they simulate key aspects of observed climate. Here, we examine whether water vapor D&A results are sensitive to model quality. The "top 10" and "bottom 10" models are selected with three different sets of skill measures and two different ranking approaches. The entire D&A analysis is then repeated with each of these different sets of more or less skillful models. Our performance metrics include the ability to simulate the mean state, the annual cycle, and the variability associated with El Niño. We find that estimates of an anthropogenic water vapor fingerprint are insensitive to current model uncertainties, and are governed by basic physical processes that are well-represented in climate models. Because the fingerprint is both robust to current model uncertainties and dissimilar to the dominant noise patterns, our ability to identify an anthropogenic influence on observed multidecadal changes in water vapor is not affected by "screening" based on model quality.

Dual chamber pacemaker implantation in dogs with atrioventricular block.

BACKGROUND: Pacemaker implantation is the treatment of choice for symptomatic bradyarrhythmias. In dogs, a single chamber system is commonly used. In human patients with high-grade 2nd- or 3rd-degree atrioventricular (AV) block, physiologic pacing is recommended, because it improves cardiac output, blood pressure, exercise tolerance, and quality of life. In dogs, this type of pacing is seldom used. HYPOTHESIS: The implantation of a dual chamber pacemaker in dogs with AV block is a feasible procedure for restoring AV synchrony. ANIMALS: Thirty-three privately owned dogs with high-grade 2nd- or 3rd-degree AV block were included. METHODS: Patient data of all dogs with AV block presented for pacemaker implantation between December 1997 and November 2004 were reviewed. RESULTS: Dual chamber pacemaker implantation with AV synchronous stimulation was successfully performed in 33/33 dogs (100%). In 9/33 (27%) major and in 12/33 (36%) minor complications were observed. Mean survival time for the patients discharged from hospital (n = 32) was 33.6 +/- 20.4 months (range, 3.9-83.5 months). CONCLUSION AND CLINICAL IMPORTANCE: Dual chamber pacing is a feasible procedure in dogs with 2nd- or 3rd-degree AV block and is not associated with a higher complication rate compared with single chamber pacemaker systems. A major advantage over ventricular demand pacemaker systems is the restoration of AV synchrony for a substantial period of time.

Identification of human-induced changes in atmospheric moisture content.

Data from the satellite-based Special Sensor Microwave Imager (SSM/I) show that the total atmospheric moisture content over oceans has increased by 0.41 kg/m(2) per decade since 1988. Results from current climate models indicate that water vapor increases of this magnitude cannot be explained by climate noise alone. In a formal detection and attribution analysis using the pooled results from 22 different climate models, the simulated "fingerprint" pattern of anthropogenically caused changes in water vapor is identifiable with high statistical confidence in the SSM/I data. Experiments in which forcing factors are varied individually suggest that this fingerprint "match" is primarily due to human-caused increases in greenhouse gases and not to solar forcing or recovery from the eruption of Mount Pinatubo. Our findings provide preliminary evidence of an emerging anthropogenic signal in the moisture content of earth's atmosphere.