Rain-fed pastoral systems are tightly connected to meteorological conditions. It is, therefore, likely that climate change, including changing atmospheric CO2 concentration, temperature, ...precipitation and patterns of climate extremes, will greatly affect pastoral systems. However, exact impacts on the productivity and carbon dynamics of these systems are still poorly understood, particularly over longtime scales. The present study assesses the potential effects of future climatic conditions on productivity and soil organic carbon (SOC) stocks of mowed and rotationally grazed grasslands in France. We used the CenW ecosystem model to simulate carbon, water, and nitrogen cycles in response to changes in environmental drivers and management practices. We first evaluated model responses to individual changes in each key meteorological variable to get better insights into the role and importance of each individual variable. Then, we used 3 sets of meteorological variables corresponding to 3 Representative Concentration Pathways (RCP 2.6, RCP 4.5 and RCP 8.5) for long-term model runs from 1975 to 2100. Finally, we used the same three RCPs to analyze the responses of modelled grasslands to extreme climate events. We found that increasing temperature slightly increased grasslands productivities but strongly reduced SOC stocks. A reduction in precipitation led to reductions of biomass and milk production but increased SOC. Conversely, doubling CO2 concentration strongly increased biomass and milk production and marginally reduced SOC. These SOC trends were unexpected. They arose because both increasing precipitation and CO2 increased photosynthetic carbon gain, but they had an even greater effect on the proportion of biomass that could be grazed. The amount of carbon remaining on site and able to contribute to SOC formation was actually reduced under both higher precipitation and CO2. The simulations under the three RCPs indicated that grassland productivity was increased, but that required higher N fertilizer application rates and also led to substantial SOC losses. We thus conclude that, while milk productivity may continue at current rates under climate change, or even increase slightly, there could be some soil C losses over the 21st century. In addition, under the highest-emission scenario, the increasing importance of extreme climate conditions (heat waves and droughts) might render conditions at our site in some years as unsuitable for milk production. It highlights the importance of tailoring farming practices to achieve the dual goals of maintaining agricultural production while safeguarding soil C stocks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rain-fed pastoral systems are tightly connected to meteorological conditions. It is, therefore, likely that climate change, including changing atmospheric CO2 concentration, temperature, ...precipitation and patterns of climate extremes, will greatly affect pastoral systems. However, exact impacts on the productivity and carbon dynamics of these systems are still poorly understood, particularly over longtime scales. The present study assesses the potential effects of future climatic conditions on productivity and soil organic carbon (SOC) stocks of mowed and rotationally grazed grasslands in France. We used the CenW ecosystem model to simulate carbon, water, and nitrogen cycles in response to changes in environmental drivers and management practices. We first evaluated model responses to individual changes in each key meteorological variable to get better insights into the role and importance of each individual variable. Then, we used 3 sets of meteorological variables corresponding to 3 Representative Concentration Pathways (RCP 2.6, RCP 4.5 and RCP 8.5) for long-term model runs from 1975 to 2100. Finally, we used the same three RCPs to analyze the responses of modelled grasslands to extreme climate events. We found that increasing temperature slightly increased grasslands productivities but strongly reduced SOC stocks. A reduction in precipitation led to reductions of biomass and milk production but increased SOC. Conversely, doubling CO2 concentration strongly increased biomass and milk production and marginally reduced SOC. These SOC trends were unexpected. They arose because both increasing precipitation and CO2 increased photosynthetic carbon gain, but they had an even greater effect on the proportion of biomass that could be grazed. The amount of carbon remaining on site and able to contribute to SOC formation was actually reduced under both higher precipitation and CO2. The simulations under the three RCPs indicated that grassland productivity was increased, but that required higher N fertilizer application rates and also led to substantial SOC losses. We thus conclude that, while milk productivity may continue at current rates under climate change, or even increase slightly, there could be some soil C losses over the 21st century. In addition, under the highest-emission scenario, the increasing importance of extreme climate conditions (heat waves and droughts) might render conditions at our site in some years as unsuitable for milk production. It highlights the importance of tailoring farming practices to achieve the dual goals of maintaining agricultural production while safeguarding soil C stocks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older ...patients with mCRC is limited.
Objective
This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy.
Methods
This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours. All were studies of adults with advanced CRC who received first-line treatment with chemotherapy plus bevacizumab, cetuximab or panitumumab, stratified by age (≥ 65 vs. < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety.
Results
In total, 999 patients from five studies were included in the analysis: 480 (48%) were aged ≥ 65 years, and 519 (52%) were aged < 65 years. Median PFS did not differ significantly between patients aged ≥ 65 and < 65 years (9.9 vs. 9.4 months; hazard ratio HR 1.01; 95% confidence interval CI 0.88–1.17). Median OS was significantly shorter in older than in younger patients (21.3 vs. 25.0 months; HR 1.21; 95% CI 1.04–1.41). There was no significant difference between older and younger patients in ORR (59 vs. 62%). Patients aged ≥ 65 years experienced significantly more treatment-related grade 3 or higher adverse events (61.67%) than did patients aged < 65 years (45.86%).
Conclusions
Biologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patients.
We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration ...(AMD).
We enrolled 1388 AMD patients with neovascular AMD or geographic atrophy and 487 unrelated control subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924), and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product of CYP46A1, was quantified by gas chromatography-mass spectrometry using an authentic deuterated internal standard in subgroups of patients and controls. The χ(2) test was used to compare categoric allelic and genotype distributions between cases and controls. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated for AMD risk, and adjusted for age and gender. Significance levels were set at P < 0.05.
The rs754203 SNP in the CYP46A1 gene was not associated with AMD (crude OR = 1.2, 95% CI = 0.9-1.4, P = 0.2). The crude OR for risk of AMD was 2.9 (95% CI = 2.4-3.4, P < 0.0001) according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0 (95% CI = 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI = 1.1-4.1, P = 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene, and carrying no risk alleles in the CFH and LOC387715 genes.
The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional studies with larger sample sizes are needed in AMD subjects at no risk in CFH and LOC387715.
Results from the SATURN registry show that an artificial urinary sphincter is the implant device of choice for patients with more severe incontinence, with better outcomes than the alternatives. ...However, the revision rate is higher for this option. It is noteworthy that incontinent patients who undergo surgery report that any improvement, whether substantial or small, is important.
The European, prospective, multicenter SATURN registry was developed to analyze surgical devices for male stress urinary incontinence. The primary objective is the cure rate during follow-up.
Efficacy, complications, patient-reported outcomes, and prognostic factors are being analyzed at various intervals during 10-yr follow-up. The results at 1-yr follow-up are presented here.
The cohort included 1046 patients (mean age 70 yr) from 28 centers in nine countries. The main cause of incontinence was radical prostatectomy (83.5%), followed by radiotherapy (4.5%), endourological procedures (9.7%), neurogenic conditions (1.0%), and trauma (0.2%). Some 19.5% of the patients underwent at least one incontinence procedure before registry inclusion. A baseline pad test was performed in 64% of the patients (mean 525 g, range 3.5–3600), urodynamics in 66%, and cystoscopy in 80%. The main implants used were AMS800 (n = 684) and Advance (n = 210) devices, followed by Atoms (n = 63) Victo/Plus (n = 33), ProACT (n = 30), and others (n = 24). A total of 896 patients had 1-yr follow-up data, of whom 164 completed a 1-yr pad test. Self-reported complete incontinence rates at baseline by device were as follows: Advance, 17%; other slings, 33%; ProACT, 0%; AMS800, 49%; other sphincter prosthesis, 100%; and overall group, 44%. The corresponding 1-yr self-reported continence rates were 73%, 37%, 50%, 76%, 11%, and 68%. Some 32% of the patients were still incontinent. Overall, 132 patients had at least one revision. Among the 110 patients with an artificial urinary sphincter (AUS), 122 revisions were performed, while there were 29 revisions for the 22 patients with a sling or ProACT device. International Consultation on Incontinence Questionnaire Short Form and EuroQol 5-dimensions 5-levels scores improved with all devices.
AUS implants are used in cases with more severe incontinence and are associated with better outcomes but more revisions than the alternatives. Patients report that every improvement is important. Choices for procedures should be made on the basis of these considerations.
We collected data from 29 urology departments in Europe on surgical treatments for patients who suffer from incontinence during exercise, sneezing, and coughing. Results after 1 year show that an artificial urinary sphincter has the best outcomes overall and for patients with heavy urine loss. However, this surgery also requires more revisions. Patients report that every improvement in continence is important to them.
While disorders of neuronal migration are associated with as much as 25% of recurrent childhood seizures, few of the genes required to establish neuronal position in cerebral cortex are known. ...Subcortical band heterotopia (SBH) and lissencephaly (LIS), two distinct neuronal migration disorders producing epilepsy and variable cognitive impairment, can be inherited alone or together in a single pedigree. Here we report a new genetic locus, XLIS, mapped by linkage analysis of five families and physical mapping of a balanced X;2 translocation in a girl with LIS. Linkage places the critical region in Xq21–q24, containing the breakpoint that maps to Xq22.3–q23 by high-resolution chromosome analysis. Markers used for somatic cell hybrid and fluorescence in situ hybridization analyses place the XLIS region within a 1 cM interval. These data suggest that SBH and X-linked lissencephaly are caused by mutation of a single gene, XLIS, that the milder SBH pheno-type in females results from random X-inactivation (Lyonization), and that cloning of genes from the breakpoint region on X will yield XLIS.
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