Pacific variability reconciles observed and modelled global mean temperature increase since 1950

Global mean temperature change simulated by climate models deviates from the observed temperature increase during decadal-scale periods in the past. In particular, warming during the ‘global warming hiatus’ in the early twenty-first century appears overestimated in CMIP5 and CMIP6 multi-model means. We examine the role of equatorial Pacific variability in these divergences since 1950 by comparing 18 studies that quantify the Pacific contribution to the ‘hiatus’ and earlier periods and by investigating the reasons for differing results. During the ‘global warming hiatus’ from 1992 to 2012, the estimated contributions differ by a factor of five, with multiple linear regression approaches generally indicating a smaller contribution of Pacific variability to global temperature than climate model experiments where the simulated tropical Pacific sea surface temperature (SST) or wind stress anomalies are nudged towards observations. These so-called pacemaker experiments suggest that the ‘hiatus’ is fully explained and possibly over-explained by Pacific variability. Most of the spread across the studies can be attributed to two factors: neglecting the forced signal in tropical Pacific SST, which is often the case in multiple regression studies but not in pacemaker experiments, underestimates the Pacific contribution to global temperature change by a factor of two during the ‘hiatus’; the sensitivity with which the global temperature responds to Pacific variability varies by a factor of two between models on a decadal time scale, questioning the robustness of single model pacemaker experiments. Once we have accounted for these factors, the CMIP5 mean warming adjusted for Pacific variability reproduces the observed annual global mean temperature closely, with a correlation coefficient of 0.985 from 1950 to 2018. The CMIP6 ensemble performs less favourably but improves if the models with the highest transient climate response are omitted from the ensemble mean

Enhancement of tissue lesion depth by dual wavelength irradiation with the Nd-YAG/KTP laser: Perspectives for laser prostatectomy

The Nd-YAG/KTP laser coagulates and vaporizes prostate tissue. The objective of this study was to investigate the combined effects of both wavelengths and to determine the irradiation parameters allowing the largest lesion volume. Chicken breast tissue was irradiated ex vivo. Consecutive 1064 and 532 nm Nd-YAG/KTP laser irradiations were performed for different combinations (30 W/10 W, 20 W/20 W, 10 W/30 W) with variable total fluence (1200 J, 2400 J, 3600 J) and compared to isofluent single wavelengths at 40 W irradiation. The depths, diameters and volumes of the total lesion as well as the vaporization effects of the 532 nm wavelength on normal and on priorly coagulated tissue were analysed. Maximum total lesion depths (p< 0.001) were found under combined Nd-YAG/KTP (20 W/20 W) irradiation conditions. Ablation efficacy of the 532 nm wavelength was reduced after prior 1064 nm irradiation, but crater depths were increased. Dual wavelength irradiation with the Nd-YAG/KTP laser induces a specific denaturation process. This may represent a new approach to increase the depth of coagulation necrosis, and thus the treated volume, thereby improving long-term result

Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test

Purpose: To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). Methods: Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. Results: Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (<0.5mm). In the 1-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline. Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD 0.56), as did eyes with high (≥0.5mm) angle sizes (0.82 logMAR (SD 0.53). UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR (SD 0.13; p=0.019)). Conclusion: Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes. Keywords: Angle alpha; Angle kappa; Decision-making; Multifocal intraocular lens; Refractive lens surgery

50 years experience with Dupuytren's contracture in the Erlangen University Hospital – A retrospective analysis of 2919 operated hands from 1956 to 2006

<p>Abstract</p> <p>Background</p> <p>Dupuytren's disease (DD) is a hand disorder mainly among the northern population. In contrast it is rare in the mediterranean population. Therefore typical habits and dietetic influences have been discussed as well as genetic predisposition. Still, since the first description by Dupuytren in 1834 only little is known about the etiology and pathogenesis of this disease. Some hints were found for a higher prevalence among people with diabetes, alcohol abuse or smoking. Also, intensive manual work or hand injuries have been discussed to have an influence on DD. To our knowledge this is the largest retrospectively evaluated series of symptomatic patients published to date. The study includes patients from the last 50 years. It was performed to show possible correlations between DD and typical risk factors such as diabetes, alcohol consumption, and smoking.</p> <p>Methods</p> <p>We retrospectively analysed all patient records with DD documented between 1956 and 2006 in the Surgical University Hospital in Erlangen. Data acquisition was conducted by reviewing the medical records from 1956 to 2006 including data from all patients who were surgically treated because of DD.</p> <p>Results</p> <p>We reviewed 2579 male and 340 female surgically treated patients with DD. More than 80% of the patients were between 40 and 70 years old. In 28.9% only the right hand was effected by DD, in 25.3% only the left hand and in 45.8% both hands. In 10.3% of all Patients suffered from Diabetes mellitus. Statistical analysis revealed no significant correlation between diabetes, alcoholism or smoking on the degree of DD in our patients.</p> <p>Conclusion</p> <p>Most data are consistent with previously published results from smaller, comparable retrospective studies with regard to right- or left handedness. We could not confirm a statistically significant correlation of DD with diabetes mellitus, severe alcohol consumption, heavy smoking or epilepsy and the stage of the disease as described in other studies. However, in the whole cohort of our operated patients during the last 50 years the prevalence of the above mentioned risk factors is slightly higher than in the normal population.</p

From Sea to Sea: Canada's Three Oceans of Biodiversity

Evaluating and understanding biodiversity in marine ecosystems are both necessary and challenging for conservation. This paper compiles and summarizes current knowledge of the diversity of marine taxa in Canada's three oceans while recognizing that this compilation is incomplete and will change in the future. That Canada has the longest coastline in the world and incorporates distinctly different biogeographic provinces and ecoregions (e.g., temperate through ice-covered areas) constrains this analysis. The taxonomic groups presented here include microbes, phytoplankton, macroalgae, zooplankton, benthic infauna, fishes, and marine mammals. The minimum number of species or taxa compiled here is 15,988 for the three Canadian oceans. However, this number clearly underestimates in several ways the total number of taxa present. First, there are significant gaps in the published literature. Second, the diversity of many habitats has not been compiled for all taxonomic groups (e.g., intertidal rocky shores, deep sea), and data compilations are based on short-term, directed research programs or longer-term monitoring activities with limited spatial resolution. Third, the biodiversity of large organisms is well known, but this is not true of smaller organisms. Finally, the greatest constraint on this summary is the willingness and capacity of those who collected the data to make it available to those interested in biodiversity meta-analyses. Confirmation of identities and intercomparison of studies are also constrained by the disturbing rate of decline in the number of taxonomists and systematists specializing on marine taxa in Canada. This decline is mostly the result of retirements of current specialists and to a lack of training and employment opportunities for new ones. Considering the difficulties encountered in compiling an overview of biogeographic data and the diversity of species or taxa in Canada's three oceans, this synthesis is intended to serve as a biodiversity baseline for a new program on marine biodiversity, the Canadian Healthy Ocean Network. A major effort needs to be undertaken to establish a complete baseline of Canadian marine biodiversity of all taxonomic groups, especially if we are to understand and conserve this part of Canada's natural heritage

A prenylated dsRNA sensor protects against severe COVID-19

INTRODUCTION Interferons (IFNs) are cytokines that are rapidly deployed in response to invading pathogens. By initiating a signaling cascade that stimulates the expression of hundreds of genes, IFNs create an antiviral state in host cells. Because IFNs heavily influence COVID-19 outcomes, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication can be inhibited by the antiviral state, it is important to understand how the individual antiviral effectors encoded by IFN-stimulated genes (ISGs) inhibit SARS-CoV-2. RATIONALE We hypothesized that IFN-stimulated antiviral effectors can inhibit SARS-CoV-2, and that variation at the loci encoding these defenses underlies why some people are more susceptible to severe COVID-19. RESULTS We used arrayed ISG expression screening to reveal that 2′-5′-oligoadenylate synthetase 1 (OAS1) consistently inhibited SARS-CoV-2 in different contexts. Using CRISPR-Cas9, we found that endogenous OAS1 makes a substantial contribution to the antiviral state by recognizing short stretches of double-stranded RNA (dsRNA) and activating RNase L. We globally mapped where OAS1 binds to SARS-CoV-2 viral RNAs and found that OAS1 binding is remarkably specific, with two conserved stem loops in the SARS-CoV-2 5′-untranslated region (UTR) constituting the principal viral target. OAS1 expression was readily detectable at the sites of infection in individuals who died of COVID-19, and specific OAS1 alleles are known to be associated with altered susceptibility to infection and severe disease. It had previously been reported that alleles containing a common splice-acceptor single nucleotide polymorphism in OAS1 (Rs10774671) were associated with less severe COVID-19. We determined that people with at least one allele with a G at this position could express a prenylated form of OAS1 (p46), whereas other individuals could not. Using a series of mutants, we found that C-terminal prenylation was necessary for OAS1 to initiate a block to SARS-CoV-2. Furthermore, confocal microscopy revealed that prenylation targeted OAS1 to perinuclear structures rich in viral dsRNA, whereas non-prenylated OAS1 was diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication. The realization that prenylation is essential for OAS1-mediated sensing of SARS-CoV-2 allowed us to examine the transcriptome of infected patients and investigate whether there was a link between the expression of prenylated OAS1 and SARS-CoV-2 disease progression. Analysis of the OAS1 transcripts from 499 hospitalized COVID-19 patients revealed that expressing prenylated OAS1 was associated with protection from severe COVID-19. Because prenylated OAS1 was so important in human cases, we wanted to determine whether horseshoe bats, the likely source of SARS-CoV-2, possessed the same defense. When we examined the genomic region where the prenylation signal should reside, retrotransposition of a long terminal repeat sequence had ablated this signal, preventing the expression of prenylated anti-CoV OAS1 in these bats. CONCLUSION C-terminal prenylation targets OAS1 to intracellular sites rich in viral dsRNA, which are likely the SARS-CoV-2 replicative organelles. Once in the right place, OAS1 binds to dsRNA structures in the SARS-CoV-2 5′-UTR and initiates a potent block to SARS-CoV-2 replication. Thus, the correct targeting of OAS1 and the subsequent inhibition of SARS-CoV-2 likely underpins the genetic association of alleles containing a G at Rs10774671 with reduced susceptibility to infection and severe disease in COVID-19. Moreover, the conspicuous absence of this antiviral defense in horseshoe bats potentially explains why SARS-CoV-2 is so sensitive to this defense in humans