Reduced Complexity Model Intercomparison Project Phase 2: Synthesizing Earth System Knowledge for Probabilistic Climate Projections.

Over the last decades, climate science has evolved rapidly across multiple expert domains. Our best tools to capture state-of-the-art knowledge in an internally self-consistent modeling framework are the increasingly complex fully coupled Earth System Models (ESMs). However, computational limitations and the structural rigidity of ESMs mean that the full range of uncertainties across multiple domains are difficult to capture with ESMs alone. The tools of choice are instead more computationally efficient reduced complexity models (RCMs), which are structurally flexible and can span the response dynamics across a range of domain-specific models and ESM experiments. Here we present Phase 2 of the Reduced Complexity Model Intercomparison Project (RCMIP Phase 2), the first comprehensive intercomparison of RCMs that are probabilistically calibrated with key benchmark ranges from specialized research communities. Unsurprisingly, but crucially, we find that models which have been constrained to reflect the key benchmarks better reflect the key benchmarks. Under the low-emissions SSP1-1.9 scenario, across the RCMs, median peak warming projections range from 1.3 to 1.7°C (relative to 1850-1900, using an observationally based historical warming estimate of 0.8°C between 1850-1900 and 1995-2014). Further developing methodologies to constrain these projection uncertainties seems paramount given the international community's goal to contain warming to below 1.5°C above preindustrial in the long-term. Our findings suggest that users of RCMs should carefully evaluate their RCM, specifically its skill against key benchmarks and consider the need to include projections benchmarks either from ESM results or other assessments to reduce divergence in future projections.

Extracellular buffer choice influences acid-base responses and gastrointestinal symptoms.

To compare the bicarbonate kinetics and gastrointestinal (GI) symptom responses between an equal dose of sodium bicarbonate and sodium citrate using delayed-release capsules. Thirteen active males (age 20.5 ± 2.1 y, height 1.8 ± 0.1 m and body mass [BM] 76.5 ± 9.6 kg) consumed either 0.3 g.kg-1 BM sodium bicarbonate, sodium citrate or a placebo, using a double-blind, randomized crossover design. Blood bicarbonate ion (HCO3-) concentration, pH and GI symptoms were measured pre-consumption and every 10 min for 180 min post-consumption. Blood HCO3- concentration (P < 0.001) and pH (P = 0.040) were significantly higher in the sodium bicarbonate condition compared with sodium citrate condition up to 3 h post-consumption. Peak blood HCO3- concentration was significantly higher with the sodium bicarbonate compared with citrate (P < 0.001). Mean GI symptom scores were lower (P = 0.037) for sodium citrate (1.5 ± 1.8 AU) than bicarbonate (2.6 ± 3.1 AU), with considerable inter-individual variability. No GI symptoms were reported following consumption of the placebo. Both substances increase HCO3- values significantly, with sodium bicarbonate causing significantly higher pH and HCO3- values than the same dose of sodium citrate, but results in slightly more severe GI symptoms.

Association between PNPLA3[G]/I148M variant, steatosis and fibrosis stage in hepatitis C virus - genetic matters.

There is an established correlation between the PNPLA3 rs738409 C > G single nucleotide polymorphism (SNP) and hepatic steatosis and fibrosis in hepatitis C virus (HCV) infected patients. However not all data is convergent regarding the exact impact of this SNP on the pattern of disease progression in different clinical settings. In this study, we aimed to further bridge the knowledge gap on this topic by investigating the role of the G allele in promoting steatosis, fibrosis and disease progression in relation to other metabolic and anthropometric host factors. Two hundred and fifty consecutive patients, previously diagnosed with chronic hepatitis C (CHC) underwent liver biopsy. Histology was assessed using the Metavir scoring system. Transient elastography was used for follow-up. Ninety-eight patients were genotyped for PNPLA3 rs738409 and followed up for fibrosis progression. PNPLA3 rs738409[G] allele was significantly correlated with severe steatosis (P = 0.04), severe fibrosis at the time of enrollment (P = 0.0005) and fibrosis progression with an OR of 10.31 (95% CI 1.06 - 99.59, P = 0.04), after a mean follow-up time of 62.85 (95%CI: 52.21 - 76.15) months. Severe steatosis at the time of enrollment had an OR of 11.02 (95% CI 1.48 - 82.09, P = 0.01) for the association with fibrosis progression. The HOMA-IR index was also positively correlated with severe fibrosis (P = 0.03) and fibrosis progression on univariate analysis (P = 0.02). PNPLA3 rs738409[G] allele is a reliable predictor for steatosis and fibrosis in CHC. The presence of G allele, along with severe steatosis and insulin resistance are significant predictors for fibrosis progression.

Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

PURPOSE: To compare the pattern of gene-specific involvement and the spectrum of variants observed in prenatal and postnatal (mean ± SD, 8.9 ± 9.4 years) cohorts tested for Noonan syndrome and related conditions. METHODS: Outcomes of sequencing panel testing were compared between prenatal (n = 845) and postnatal (n = 409) cohorts. RESULTS: PTPN11 and SOS1 harbored the majority of observed variants in both prenatal and postnatal cohorts, and BRAF, HRAS, KRAS, MAP2K1, MAP2K2, RAF1, and SHOC2 had similarities in their pattern of involvement in both cohorts. PTPN11 was the largest contributor of pathogenic variants and had the lowest frequency of variants of uncertain significance (VUS). SOS1 had the highest VUS frequency in both cohorts. The overall VUS frequency was twice as high in prenatal specimens (58.1 vs. 29.3%). PTPN11 and SOS1 had a 1.5-fold higher VUS frequency in the prenatal cohort (10.7 vs. 7.4% and 95 vs. 61.1%, respectively). The diagnostic yield was 3.7% for prenatal samples, with a higher yield of 12.3% in fetuses with cystic hygroma as a sole finding, and 21.3% for postnatal. CONCLUSION: Comparison of prenatal versus postnatal specimens demonstrates that the pattern of specific gene involvement is similar, whereas the classification spectrum of observed variants differs considerably.

Correction: Comparative assessment of gene-specific variant distribution in prenatal and postnatal cohorts tested for Noonan syndrome and related conditions.

The original version of this Article contained an error in the spelling of the author N. T. Leach, which was incorrectly given as N. L. Leach. This has been corrected in both the PDF and HTML versions of the Article.

Vertical imbalance induced by prism-ballasted soft toric contact lenses fitted unilaterally.

Fitting a prism-ballasted soft toric contact lens unilaterally may potentially induce a vergence error that the subject cannot compensate. In the present study, a prism-ballasted (1.5Delta base down) soft toric contact lens was fitted in the right eye only of 10 subjects with normal binocular vision. The effect on binocular vision was evaluated by measuring vertical phoria adaptation and vertical fixation disparity adaptation. The results show that the vertical vergence error induced was well compensated and fully adapted to. However, care might be needed when fitting these lenses unilaterally in subjects with vertical phoria-related problems.

The application of spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) technology to determine the chromosomal content(s) of micronuclei.

DNA loss by the process of micronucleation is associated with aging, cancer and environmental exposure. The primary aim of this study was to identify the chromosomal origin of the DNA excluded into micronuclei (MN). This was achieved using a novel application of SKY and FISH technologies. Cytochalasin B (Cyt B)-treated lymphocyte cultures from three females (aged 28, 42 and 72) were analyzed. SKY revealed that the majority of MN (89.8, 82.9, and 97.6% in the 28-, 42- and 72-year-old (y.o.), respectively) had a uniform, single color, suggesting that they were comprised of DNA from a single chromosome. Using a pancentromeric probe, most of the MN (82% in 28 y.o., 69% in 42 y.o. and 80% in 72 y.o.) had one centromere signal present. Overall, the confirmation studies (using FISH with chromosome-specific WCP) were in agreement with the SKY chromosomal assignments for 71.1% of the MN. Although the SKY analysis showed that all of the 23 chromosomes (22 autosomes and the X chromosome) could be present in the MN, overall, the X chromosome was seen most frequently. DNA from the X chromosome was seen in 50.6% of MN in the 42 y.o. individual, whereas in the 28 and 72 y.o. it was seen in 12.2 and 7.1% of MN, respectively. This difference (P<0.0001) in the frequencies of X chromosome exclusion into MN among individuals was independently confirmed using a single whole chromosome painting probe (WCP) for the X chromosome. SKY also showed variation in the frequency of autosomal exclusion into MN between chromosomes and between females. Collectively, this study supports the hypothesis that the majority of MN contain DNA from a single, monocentric chromosome. The use of SKY technology for the identification of the chromosomal content(s) of MN provides an opportunity for expansion of our knowledge of the chromosomal changes that accompany MN formation.

Alternative futures for world cereal and meat consumption.

Fundamental changes in the global structure of food demand will lead to an extraordinary increase in the importance of developing countries in global food markets. Economic growth in developing countries is changing consumption patterns, with slower growth (and in many countries actual declines) in per capita food consumption of grains and rapidly growing per capita and total meat consumption, combined with induced growth in cereal feed consumption. The present paper examines the hypothesis, suggested by some researchers, that high-meat diets in developed countries limit improvement in food security in developing countries. These analysts argue that reduced meat consumption in developed countries would release cereals from livestock feed to food for poorer populations, thus improving food security in developing countries. Using the International Food Policy Research Institute (Washington, DC, USA) global food projections model, the international model for policy analysis of agricultural commodities and trade (see Rosegrant et al. 1995), we first analyse the implications for future global cereal and meat supply and demand resulting from changes in global income, population growth and other structural changes, then simulate alternative scenarios to examine the effect of large reductions in meat consumption in developed countries on food consumption and food security in developing countries. The paper shows that while the long-term prospects for food supply, demand and trade indicate a strengthening of world cereal and livestock markets, the improvement in food security in the developing world will be slow, and changes in the dietary patterns in developed countries are not an effective route to improvement in food security in developing countries.

Short- and long-term repeatability of Visioptic Alcon EyeMap (Visioptic EH-270) corneal topographer on normal human corneas.

The purpose of this study was to examine the short-term and long-term (6 months) repeatability of the Alcon EyeMap (Visioptic EH-270)a Computerized Corneal Topographer on normal eyes. Three measurements were taken on both eyes of 39 subjects with the corneal topographer. Both eyes of seven of these subjects were measured 6 months later in order to evaluate long-term repeatability. The data showed that short-term reliability of the instrument was acceptable with a mean standard deviation (SD) < or = 0.5 D up to 3 mm (6-mm optical zone) from the center of the normal cornea. Beyond that distance, SD's of repeated measures increased systematically, making the results less useful. Long-term repeatability of the instrument over a 6-month period was acceptable clinically, although statistically significant differences were noted.

Monocular vs. stereoscopic measurement of cup-to-disc ratios.

Stereoscopic viewing of the optic nerve head and cup has been reported to provide more reliable cup-to-disc (C/D) ratio estimates. We investigated the variability in C/D ratio estimates among three experienced optometric clinicians using conventional direct ophthalmoscopy and indirect biomicroscopy with the Volk 90 D lens. The pupils of 21 subjects were dilated and the discs assessed randomly by each examiner for the determination of the C/D ratio. Analysis of variance indicates that the two methods are not significantly different from each other when comparing interexaminer reliability. However, for a particular examiner, one method may be more effective than the other.

The Hirschberg test: correlation with corneal radius and axial length.

The results of this study indicate that the axial length is not strongly associated with the Hirschberg formula, and therefore the axial length does not have to be considered when measuring an ocular deviation with the Hirschberg test. This study does demonstrate an association between the radius of curvature of the cornea and the Hirschberg formula. For patients with keratometer readings below 46 D, the use of the standard Hirschberg formula, 1 mm = 22 delta, is appropriate. For patients with keratometer readings greater than 46 D, and with deviations greater than about 30 delta, the use of the Hirschberg formula, 1 mm = 27 delta, is more appropriate. When performing the Hirschberg test on infants up to about 2 months of age, the use of the higher Hirschberg formula would probably be more appropriate because this age group often has higher keratometer readings.

Rigid lens base curve stability upon hydrogen peroxide disinfection.

Because of the possibility of transmitting communicable diseases, in particular the HIV virus, it has been recommended that all diagnostic contact lenses, including rigid lenses, be disinfected after each use. Hydrogen peroxide is a recommended disinfection agent, but its effect on rigid lens polymers is relatively unknown. We soaked 50 lenses of 5 different polymers in 3% hydrogen peroxide for 10 min and measured the base curves to determine if any changes occurred. Our results showed no statistically significant change in base curve for the lenses measured, but 22% of the lenses did exhibit a small amount of warpage (mean 0.0382 mm) of the base curve. We were not able to determine what caused these lenses, and not all the lenses, to warp. Under the conditions of this study, hydrogen peroxide does not appear to cause clinically significant parameter changes, but lenses should be checked for warpage before use.

Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications.

Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.

The subjective quality (SQF) of Bausch and Lomb SoflensTM.

The visual acutiy of a person is examined in terms of his response to a unique target. This target is a sequence of black bars on a white background, where the spacing of the bars and their width is governed by a log periodic function. The generation of these targets is performed by a PDP-8 computer connected to an X-Y plotter. There are six sets of bars which vary in contrast and frequency. In a clinical situation, an observer notates the position where he can no longer resolve the bar pattern. A recroding of these positions produces a Subjective Quality Function (SQF) curve for the individual. On fitting with soft contact lenses, a new SQF curve is generated. A comparison of the SQF for soft lenses with that for spectacle corrections is given.

Corneal hydration changes during the normal menstrual cycle--a preliminary study.

PIP: A study is described that was undertaken to determine if significant changes in corneal hydration and curvature occur during the normal menstrual cycle over an extended period of time. The right eyes of 6 young women ranging in age from 19 to 22 years, were measured for corneal thickness and curvature over a 2-month period. 5 readings of corneal thickness and 3 readings of corneal curvature were taken 3 times per week on the same day and hour for each subject. Each subject maintained a calendar of menstrual activity for the 2-month period and submitted it on completion of the experiment. The testing days were converted to the days of the menstrual cycle by matching chronological dates. The mean menstrual cycle length was 27.5 days. The mean menstrual phase was 5.5 days. Results from the data collected showed that the mean corneal thickness curve during 1 menstrual cycle closely paralleled the bimodal nature of the estrogen levels in plasma. A relationship of the corneal curvature change to corneal thickness change, of the levels found here (approximately 9%), was lacking. This study demonstrated that there is a significant change in corneal hydration during the normal menstrual cycle. Apparently, the change is associated with the effects of estrogen more than with progesterone. The authors believe one might assume ready access of these hormones via the aqueous humor or tear film because of their high lipid solubility. They suggest that another possibility would be an indirect action of hormones on the cornea via their effects on tear film osmolarity.^ieng