Bias adjustment and ensemble recalibration methods for seasonal forecasting: a comprehensive intercomparison using the C3S dataset

This work presents a comprehensive intercomparison of diferent alternatives for the calibration of seasonal forecasts, ranging from simple bias adjustment (BA)-e.g. quantile mapping-to more sophisticated ensemble recalibration (RC) methods- e.g. non-homogeneous Gaussian regression, which build on the temporal correspondence between the climate model and the corresponding observations to generate reliable predictions. To be as critical as possible, we validate the raw model and the calibrated forecasts in terms of a number of metrics which take into account diferent aspects of forecast quality (association, accuracy, discrimination and reliability). We focus on one-month lead forecasts of precipitation and temperature from four state-of-the-art seasonal forecasting systems, three of them included in the Copernicus Climate Change Service dataset (ECMWF-SEAS5, UK Met Ofce-GloSea5 and Météo France-System5) for boreal winter and summer over two illustrative regions with diferent skill characteristics (Europe and Southeast Asia). Our results indicate that both BA and RC methods efectively correct the large raw model biases, which is of paramount importance for users, particularly when directly using the climate model outputs to run impact models, or when computing climate indices depending on absolute values/thresholds. However, except for particular regions and/or seasons (typically with high skill), there is only marginal added value-with respect to the raw model outputs-beyond this bias removal. For those cases, RC methods can outperform BA ones, mostly due to an improvement in reliability. Finally, we also show that whereas an increase in the number of members only modestly afects the results obtained from calibration, longer hindcast periods lead to improved forecast quality, particularly for RC methods.This work has been funded by the C3S activity on Evaluation and Quality Control for seasonal forecasts. JMG was partially supported by the project MULTI-SDM (CGL2015-66583-R, MINECO/FEDER). FJDR was partially funded by the H2020 EUCP project (GA 776613)

Hepatitis B Virus infection in HIV-positive population in Brazil: results of a survey in the state of Mato Grosso and a comparative analysis with other regions of Brazil

BACKGROUND: End-stage liver disease is currently a major concern among HIV-positive individuals due to co-infection with hepatotropic virus. Hepatitis C has been pointed out as a remarkable factor for that. More recently, hepatitis B virus (HBV) infection has also been found to play a role on liver disease in this population. HIV-HBV co-infection prevalence remains largely unknown in vast areas of Brazil. The objective of the present study was to estimate the prevalence of HBV and HDV infection in HIV-infected subjects living in the state of Mato Grosso, in the Central region of Brazil, and compare it to other Brazilian studies. We also assess epidemiologic data regarding risk factors and vaccinal status. METHODS: HIV-positive individuals followed at the Central Laboratory of the Department of Public Health of Mato Grosso in the city of Cuiabá composed the sample. Participants answered a specific questionnaire and had a blood sample taken and tested for serologic markers. RESULTS: A thousand individuals were interviewed and tested for HBsAg, anti-HBc, anti-HBs and anti-HDV if positive for HBsAg. Measurements of CD4 and viral load for HIV-1 were also performed. Overall prevalence of HBV exposure (anti-HBc +ve) was 40.0%, and 3.7% for HBsAg. This prevalence data was similar or slightly lower than for other Brazilian regions, which ranged from 40% and 3% to 71% and 24%, respectively. Testing for anti-HDV in the 37 HBsAg positive patients was positive in only one subject. Factors that showed independent association with HBV exposure, after adjustment, were: male gender, older age groups, tattooing, and reporting more than ten sexual partners throughout life (p < 0.01). Eighty-one (27.5%) out of 291 HBV-unexposed individuals who reported vaccination were anti-HBs positive. Anti-HBs prevalence was higher among those who had higher levels of CD4 by multivariate analysis. CONCLUSION: Our data showed HBV infection prevalence similar or slightly lower than that reported in other regions of Brazil. In addition, our data revealed a less important role for drug injection in the spread of HIV and HBV in Mato Grosso compared to other regions of the country. The high rate of non-vaccinated subjects among this HBV-unexposed, HIV-infected population is a matter of considerable health concern in this region. The relationship between CD4 levels and HBV vaccine response found in the present study reinforces the need of keeping health care workers alert to this issue

Dentin deproteinization effect on bond strength of self-adhesive resin cements

This study examined the effect of deproteinization on the bond strength between self-adhesive resin cements and dentin surfaces that were untreated (control), acid-etched, or acid-etched and subjected to a post-etch deproteinization treatment. Cylinders of RelyX Unicem or BisCem (n = 6) cement were build-up on the dentin surfaces and tested to determine shear strength. The results were analyzed using two-way ANOVA and Tukey's test (5%). While neither dentin pretreatment improved the bond strength for RelyX Unicem, deproteinization treatments resulted in greater bond strength in BisCem specimens while acid etching alone did not improve the performance of the material

Sometimes Sperm Whales (Physeter macrocephalus) Cannot Find Their Way Back to the High Seas: A Multidisciplinary Study on a Mass Stranding

BACKGROUND: Mass strandings of sperm whales (Physeter macrocephalus) remain peculiar and rather unexplained events, which rarely occur in the Mediterranean Sea. Solar cycles and related changes in the geomagnetic field, variations in water temperature and weather conditions, coast geographical features and human activities have been proposed as possible causes. In December 2009, a pod of seven male sperm whales stranded along the Adriatic coast of Southern Italy. This is the sixth instance from 1555 in this basin. METHODOLOGY/PRINCIPAL FINDINGS: Complete necropsies were performed on three whales whose bodies were in good condition, carrying out on sampled tissues histopathology, virology, bacteriology, parasitology, and screening of veins looking for gas emboli. Furthermore, samples for age determination, genetic studies, gastric content evaluation, stable isotopes and toxicology were taken from all the seven specimens. The animals were part of the same group and determined by genetic and photo-identification to be part of the Mediterranean population. Causes of death did not include biological agents, or the "gas and fat embolic syndrome", associated with direct sonar exposure. Environmental pollutant tissue concentrations were relatively high, in particular organochlorinated xenobiotics. Gastric content and morphologic tissue examinations showed a prolonged starvation, which likely caused, at its turn, the mobilization of lipophilic contaminants from the adipose tissue. Chemical compounds subsequently entered the blood circulation and may have impaired immune and nervous functions. CONCLUSIONS/SIGNIFICANCE: A multi-factorial cause underlying this sperm whales' mass stranding is proposed herein based upon the results of postmortem investigations as well as of the detailed analyses of the geographical and historical background. The seven sperm whales took the same "wrong way" into the Adriatic Sea, a potentially dangerous trap for Mediterranean sperm whales. Seismic surveys should be also regarded as potential co-factors, even if no evidence of direct impact has been detected

Skeleton of an unusual cat-sized marsupial relative (Metatheria: Marsupialiformes) from the middle Eocene (Lutetian: 44-43 million years ago) of Turkey

We describe a near-complete, three-dimensionally preserved skeleton of a metatherian (relative of modern marsupials) from the middle Eocene (Lutetian: 44–43 million years ago) Lülük member of the Uzunçarşıdere Formation, central Turkey. With an estimated body mass of 3–4 kg, about the size of a domestic cat (Felis catus) or spotted quoll (Dasyurus maculatus), it is an order of magnitude larger than the largest fossil metatherians previously known from the Cenozoic of the northern hemisphere. This new taxon is characterised by large, broad third premolars that probably represent adaptations for hard object feeding (durophagy), and its craniodental morphology suggests the capacity to generate high bite forces. Qualitative and quantitative functional analyses of its postcranial skeleton indicate that it was probably scansorial and relatively agile, perhaps broadly similar in locomotor mode to the spotted quoll, but with a greater capacity for climbing and grasping. Bayesian phylogenetic analysis of a total evidence dataset comprising 259 morphological characters and 9kb of DNA sequence data from five nuclear protein-coding genes, using both undated and “tip-and-node dating” approaches, place the new taxon outside the marsupial crown-clade, but within the clade Marsupialiformes. It demonstrates that at least one metatherian lineage evolved to occupy the small-medium, meso- or hypo-carnivore niche in the northern hemisphere during the early Cenozoic, at a time when there were numerous eutherians (placentals and their fossil relatives) filling similar niches. However, the known mammal fauna from Uzunçarşıdere Formation appears highly endemic, and geological evidence suggests that this region of Turkey was an island for at least part of the early Cenozoic, and so the new taxon may have evolved in isolation from potential eutherian competitors. Nevertheless, the new taxon reveals previously unsuspected ecomorphological disparity among northern hemisphere metatherians during the first half of the Cenozoic

The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion

From Springer Nature via Jisc Publications RouterHistory: received 2020-04-21, rev-recd 2021-03-23, accepted 2021-04-14, registration 2021-04-15, pub-electronic 2021-05-12, online 2021-05-12, pub-print 2021-06-10Publication status: PublishedFunder: Worldwide Cancer Research; doi: https://doi.org/10.13039/100011713; Grant(s): 15-1283Funder: RCUK | MRC | Medical Research Foundation; doi: https://doi.org/10.13039/501100009187; Grant(s): MC_PC_18056Abstract: There is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Mechanistically, our in vitro data revealed that ERK5 was critical for maintaining the invasive capability of triple-negative breast cancer (TNBC) cells through focal adhesion protein kinase (FAK) activation. Specifically, we found that phosphorylation of FAK at Tyr397 was controlled by a kinase-independent function of ERK5. Accordingly, silencing ERK5 in mammary tumor grafts impaired FAK phosphorylation at Tyr397 and suppressed TNBC cell metastasis to the lung without preventing tumor growth. Collectively, these results establish a functional relationship between ERK5 and FAK signaling in promoting malignancy. Thus, targeting the oncogenic ERK5-FAK axis represents a promising therapeutic strategy for breast cancer exhibiting aggressive clinical behavior