•Precipitation extremes in La Plata Basin (South America) are discussed.•Results of observations and model simulations are part of CLARIS-LPB Project.•Pacific, Atlantic and Indian Oceans SST ...anomalies contribute to the extremes.•The soil moisture in the region contribute to precipitation intensity.
Monthly and daily precipitation extremes over La Plata Basin (LPB) are analyzed in the framework of the CLARIS-LPB Project. A review of the studies developed during the project and results of additional research are presented and discussed. Specific aspects of analysis are focused on large-scale versus local processes impacts on the intensity and frequency of precipitation extremes over LPB, and on the assessment of specific wet and dry spell indices and their changed characteristics in future climate scenarios. The analysis is shown for both available observations of precipitation in the region and ad-hoc global and regional models experiments. The Pacific, Indian and Atlantic Oceans can all impact precipitation intensity and frequency over LPB. In particular, considering the Pacific sector, different types of ENSO events (i.e. canonical vs Modoki or East vs Central) have different influences. Moreover, model projections indicate an increase in the frequency of precipitation extremes over LPB during El Niño and La Ninã events in future climate. Local forcings can also be important for precipitation extremes. Here, the feedbacks between soil moisture and extreme precipitation in LPB are discussed based on hydric conditions in the region and model sensitivity experiments. Concerning droughts, it was found that they were more frequent in the western than in the eastern sector of LPB during the period of 1962–2008. On the other hand, observations and model experiments agree in that the monthly wet extremes were more frequent than the dry extremes in the northern and southern LPB sectors during the period 1979–2001, with higher frequency in the south.
Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer ...does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.
In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18–70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0–1 from 81 hospitals in Italy. Eligible patients were randomly allocated (1:1:1:1) to one of the four following study groups: four cycles of standard-interval intravenous EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) on day 1 every 3 weeks, followed by four cycles of intravenous paclitaxel (175 mg/m2) on day 1 every 3 weeks (q3EC-P group); four cycles of intravenous FEC (fluorouracil 600 mg/m2, epirubicin 90 mg/m2, and cyclophosphamide 600 mg/m2) on day 1 every 3 weeks, followed by four cycles of intravenous paclitaxel (175 mg/m2) on day 1 every 3 weeks (q3FEC-P group); dose-dense EC-P regimen, with the same doses and drugs as the q3EC-P group but administered every 2 weeks (q2EC-P group); and the dose-dense FEC-P regimen, with the same doses and drugs as the q3FEC-P group but given every 2 weeks (q2FEC-P). Randomisation, with stratification by centre, with permuted blocks of size 12, was done with a centralised, interactive, internet-based system that randomly generated the treatment allocation. The primary endpoint was disease-free survival in the intention-to-treat population, comparing different chemotherapy schedule (dose-dense vs standard-dose intervals) and regimen (FEC-P vs EC-P). Safety population included all patients that received at least one dose of any study drug according to the treatment received. This trial is registered with ClinicalTrials.gov, NCT00433420, and is now closed.
Between April 24, 2003, and July 3, 2006, 2091 patients were randomly assigned to treatment: 545 to q3EC-P, 544 to q3FEC-P, 502 to q2EC-P, and 500 to q2FEC-P. 88 patients were enrolled in centres providing only standard interval schedule and were assigned only to q3FEC-P and q3EC-P; thus, 2091 patients were included in the intention-to-treat analysis for the comparison of EC-P (1047 patients) versus FEC-P (1044 patients) and 2003 patients were included in the intention-to-treat analysis for the comparison of dose-dense (1002 patients) versus standard interval analysis (1001 patients). After a median follow-up of 15·1 years (IQR 8·4–16·3), median disease-free survival was not significantly different between FEC-P and EC-P groups (17·09 years 95% CI 15·51–not reached vs not reached 17·54–not reached; unadjusted hazard ratio 1·12 95% CI 0·98–1·29; log-rank p=0·11). Median disease-free survival was significantly higher in the dose-dense interval group than the standard-interval group (not reached 95% CI 17·45–not reached vs 16·52 14·24–17·54; 0·77 95% CI 0·67–0·89; p=0·0004). The most common grade 3–4 adverse events were neutropenia (200 37% of 536 patients in the q3EC-P group vs 257 48% of 533 in the q3FEC-P group vs 50 10% of 496 q2EC-P vs 97 20% of 492) and alopecia (238 44% vs 249 47% vs 228 46% vs 235 48%). During extended follow-up, no further grade 3–4 adverse events or deaths related to toxic-effects were reported. Treatment-related serious adverse events were reported in nine (2%) patients in the q3EC-P group, seven (1%) in the q3FEC-P group, nine (2%) in the q2EC-P group, and nine (2%) in the q2FEC-P group. No treatment-related deaths occurred.
Updated results from the GIM2 study support that optimal adjuvant chemotherapy for patients with high-risk early breast cancer should not include fluorouracil and should use a dose-dense schedule.
Bristol-Myers Squibb, Pharmacia, Dompè Biotec Italy, Italian Ministry of Health, Fondazione Italiana per la Ricerca sul Cancro, and Alliance Against Cancer.
•We test the inertia effect using a panel data with the same set of individuals.•We have RP/SP information before a new tram implementation and RP information two years later.•We found an inertia ...effect between the RP waves which increases the probability of choosing the car.•Taking into account only the RP-SP outcomes before tram might have led to wrong conclusions.•Models with inertia provide better fit to data and affect direct and cross-elasticities of all modes.
Ignoring the inertia effects on transport-mode choice behavior may lead to erroneous decisions in transport policy. Around changes in the transport system, the majority of studies on inertia have relied on combining Revealed Preferences (RP) and Stated Preferences (SP) obtained prior to the introduction of new transport modes and measuring inertia as the effect that the real choices have on the choices in the hypothetical new scenarios. In this study, we analyze the role of the inertia using a novel panel data from the same set of individuals composed of two waves. The first wave was gathered before a new tram came into service and consisted of a RP survey and a SP survey which included the new public tram as a hypothetical alternative. The second wave consisted of a RP survey conducted two years later, after the tram started operating. Using these two waves, we estimate panel mixed logit models and found a significant inertia effect only between the RP waves which, having accounted for changes in other factors, increases the probability of choosing the car after the tram implementation. However, we did not find inertia effect on SP, hence taking into account only the RP-SP outcomes before tram might have led to wrong conclusions about the effect of the transport intervention on the modal share. Furthermore, we compare models with and without inertia effect and conclude that the models with inertia provide better fit to data, smaller direct car elasticities and increasing asymmetric effects between the car and public transport.
Developing organs require iron for a myriad of functions, but embryos deleted of the major adult transport proteins, transferrin or its receptor transferrin receptor1 (TfR1−/−), still initiate ...organogenesis, suggesting that non-transferrin pathways are important. To examine these pathways, we developed chimeras composed of fluorescence-tagged TfR1−/− cells and untagged wild-type cells. In the kidney, TfR1−/− cells populated capsule and stroma, mesenchyme and nephron, but were underrepresented in ureteric bud tips. Consistently, TfR1 provided transferrin to the ureteric bud, but not to the capsule or the stroma. Instead of transferrin, we found that the capsule internalized ferritin. Since the capsule expressed a novel receptor called Scara5, we tested its role in ferritin uptake and found that Scara5 bound serum ferritin and then stimulated its endocytosis from the cell surface with consequent iron delivery. These data implicate cell type-specific mechanisms of iron traffic in organogenesis, which alternatively utilize transferrin or non-transferrin iron delivery pathways.
Exome sequencing is emerging as a first-line diagnostic method in some clinical disciplines, but its usefulness has yet to be examined for most constitutional disorders in adults, including chronic ...kidney disease, which affects more than 1 in 10 persons globally.
We conducted exome sequencing and diagnostic analysis in two cohorts totaling 3315 patients with chronic kidney disease. We assessed the diagnostic yield and, among the patients for whom detailed clinical data were available, the clinical implications of diagnostic and other medically relevant findings.
In all, 3037 patients (91.6%) were over 21 years of age, and 1179 (35.6%) were of self-identified non-European ancestry. We detected diagnostic variants in 307 of the 3315 patients (9.3%), encompassing 66 different monogenic disorders. Of the disorders detected, 39 (59%) were found in only a single patient. Diagnostic variants were detected across all clinically defined categories, including congenital or cystic renal disease (127 of 531 patients 23.9%) and nephropathy of unknown origin (48 of 281 patients 17.1%). Of the 2187 patients assessed, 34 (1.6%) had genetic findings for medically actionable disorders that, although unrelated to their nephropathy, would also lead to subspecialty referral and inform renal management.
Exome sequencing in a combined cohort of more than 3000 patients with chronic kidney disease yielded a genetic diagnosis in just under 10% of cases. (Funded by the National Institutes of Health and others.).
Abstract Change over recent decades in the world's five Mediterranean Climate Regions (MCRs) of quantities of relevance to water resources, ecosystems and fire are examined for all seasons and placed ...in the context of changes in large‐scale circulation. Near‐term future projections are also presented. It is concluded that, based upon agreement between observational data sets and modelling frameworks, there is strong evidence of radiatively‐driven drying of the Chilean MCR in all seasons and southwest Australia in winter. Observed drying trends in California in fall, southwest southern Africa in fall, the Pacific Northwest in summer and the Mediterranean in summer agree with radiatively‐forced models but are not reproduced in a model that also includes historical sea surface temperature (SST) forcing, raising doubt about the human‐origin of these trends. Observed drying in the Mediterranean in winter is stronger than can be accounted for by radiative forcing alone and is also outside the range of the SST‐forced ensemble. It is shown that near surface vapour pressure deficit (VPD) is increasing almost everywhere but that, surprisingly, this is contributed to in the Southern Hemisphere subtropics to mid‐latitudes by a decline in low‐level specific humidity. The Southern Hemisphere drying, in terms of precipitation and specific humidity, is related to a poleward shift and strengthening of the westerlies with eddy‐driven subsidence on the equatorward side. Model projections indicate continued drying of Southern Hemisphere MCRs in winter and spring, despite ozone recovery and year‐round drying in the Mediterranean. Projections for the North American MCR are uncertain, with a large contribution from internal variability, with the exception of drying in the Pacific Northwest in summer. Overall the results indicate continued aridification of MCRs other than in North America with important implications for water resources, agriculture and ecosystems.
A multi-model set of atmospheric simulations forced by historical sea surface temperature (SST) or SSTs plus Greenhouse gases and aerosol forcing agents for the period of 1950-1999 is studied to ...identify and understand which components of the Asian-Australian monsoon (A-AM) variability are forced and reproducible. The analysis focuses on the summertime monsoon circulations, comparing model results against the observations. The priority of different components of the A-AM circulations in terms of reproducibility is evaluated. Among the subsystems of the wide A-AM, the South Asian monsoon and the Australian monsoon circulations are better reproduced than the others, indicating they are forced and well modeled. The primary driving mechanism comes from the tropical Pacific. The western North Pacific monsoon circulation is also forced and well modeled except with a slightly lower reproducibility due to its delayed response to the eastern tropical Pacific forcing. The simultaneous driving comes from the western Pacific surrounding the maritime continent region. The Indian monsoon circulation has a moderate reproducibility, partly due to its weakened connection to June-July-August SSTs in the equatorial eastern Pacific in recent decades. Among the A-AM subsystems, the East Asian summer monsoon has the lowest reproducibility and is poorly modeled. This is mainly due to the failure of specifying historical SST in capturing the zonal land-sea thermal contrast change across the East Asia. The prescribed tropical Indian Ocean SST changes partly reproduce the meridional wind change over East Asia in several models. For all the A-AM subsystem circulation indices, generally the MME is always the best except for the Indian monsoon and East Asian monsoon circulation indices.
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation ...in up to 12% of patients with CAKUT.
We applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice. In consanguineous or multiplex families, we additionally performed a search for novel monogenic causes of CAKUT.
In 29 families (13%), we detected a causative mutation in a known gene for isolated or syndromic CAKUT that sufficiently explained the patient's CAKUT phenotype. In three families (1%), we detected a mutation in a gene reported to cause a phenocopy of CAKUT. In 15 of 155 families with isolated CAKUT, we detected deleterious mutations in syndromic CAKUT genes. Our additional search for novel monogenic causes of CAKUT in consanguineous and multiplex families revealed a potential single, novel monogenic CAKUT gene in 19 of 232 families (8%).
We identified monogenic mutations in a known human CAKUT gene or CAKUT phenocopy gene as the cause of disease in 14% of the CAKUT families in this study. Whole-exome sequencing provides an etiologic diagnosis in a high fraction of patients with CAKUT and will provide a new basis for the mechanistic understanding of CAKUT.
Extreme events in the La Plata basin Carril, Andrea F.; Cavalcanti, Iracema F. A.; Menéndez, C. G. ...
Climate research,
01/2016, Letnik:
68, Številka:
2-3
Journal Article
Recenzirano
Odprti dostop
Extreme climate events over the La Plata basin (LPB) can produce significant impacts due to the importance of the regional agriculture and hydroelectric power production for the local economy. ...Progress on describing, projecting and understanding extremes in LPB, in the framework of the CLARIS-LPB Europe-South America Network for Climate Change Assessment and Impact Studies in La Plata Basin Project, are reviewed. The paper is based on recent studies and publications, as well as some new diagnostics as indicators of works in progress, and can be considered as an update for the LPB region of previous reviews by Cavalcanti et al. (2015; J Hydrol 523:211–230) and Rusticucci (2012; Atmos Res 106:1–17). Despite the significant advances on regional extremes, some gaps have been identified, and many challenges remain. Much of the recent progress considers temperature and precipitation extremes on timescales varying from synoptic to long-term variability and climate change, essential for impact and vulnerability assessments. Research lines on extremes requiring further efforts include the relative roles of local versus remote forcings, the impact of land use and land management changes, the specific role of soil moisture and land-atmosphere feedbacks as catalysts for heat waves, the impact of the local inhomogeneities in soil moisture, feedback and uncertainties in projections of extremes, as well as seasonal forecast and climate change attribution studies. We suggest combining intensive monitoring and modelling to address these issues.
The main drivers of the continental Northern Hemisphere snow cover are investigated in the 1979–2014 period. Four observational datasets are used as are two large multi-model ensembles of ...atmosphere-only simulations with prescribed sea surface temperature (SST) and sea ice concentration (SIC). A first ensemble uses observed interannually varying SST and SIC conditions for 1979–2014, while a second ensemble is identical except for SIC with a repeated climatological cycle used. SST and external forcing typically explain 10 % to 25 % of the snow cover variance in model simulations, with a dominant forcing from the tropical and North Pacific SST during this period. In terms of the climate influence of the snow cover anomalies, both observations and models show no robust links between the November and April snow cover variability and the atmospheric circulation 1 month later. On the other hand, the first mode of Eurasian snow cover variability in January, with more extended snow over western Eurasia, is found to precede an atmospheric circulation pattern by 1 month, similar to a negative Arctic oscillation (AO). A decomposition of the variability in the model simulations shows that this relationship is mainly due to internal climate variability. Detailed outputs from one of the models indicate that the western Eurasia snow cover anomalies are preceded by a negative AO phase accompanied by a Ural blocking pattern and a stratospheric polar vortex weakening. The link between the AO and the snow cover variability is strongly related to the concomitant role of the stratospheric polar vortex, with the Eurasian snow cover acting as a positive feedback for the AO variability in winter. No robust influence of the SIC variability is found, as the sea ice loss in these simulations only drives an insignificant fraction of the snow cover anomalies, with few agreements among models.
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