178 research outputs found
Improving evapotranspiration estimation in pasture and native vegetation models using flux tower data, remote sensing and global optimisation
GRASP is a biophysical model of soil water balance, pasture growth and animal production developed for northern Australian grasses in wooded and non-wooded systems. The intention of this work is to improve predictions from the GRASP model of evapotranspiration, soil water balance and subsequent pasture biomass and cover in tree-grass systems. This work feeds into the operational modelling system of GRASP that is disseminated through the FORAGE and AussieGRASS online systems, available at the Long Paddock website (https://www.longpaddock.qld.gov.au/forage). The GRASP model operates at 3 different scales: Cedar GRASP (paddock scale), FORAGE (property scale) and AussieGRASS (continental scale for Australia). The Cedar version is used for model development and research on grazing trials in Queensland and the Northern Territory. FORAGE is an online system for Queensland that generates and distributes customised PDF reports with information for individual properties. Currently over 2000 reports are requested per month for use by extension providers (government and private), consultants (valuers, agents), researchers (universities and government) and land managers. AussieGRASS products are currently used within the Queensland government to assist with drought declaration assessments and a monthly Climate Outlook and Review delivered through https://www.usq.edu.au/research/environmental-sciences/qdmc-drought This paper documents the parameterisation and improvements to GRASP for estimating evapotranspiration in tree-grass systems. GRASP was overestimating the daily rate of evapotranspiration, particularly in wooded systems during the first days after rainfall events, with evapotranspiration often exceeding 1.3 times pan evaporation (Allen et al., 1998). Model partitioning of evapotranspiration into soil evaporation, grass and tree transpiration also needed adjustment to prevent excessive water loss. Incorporating daily measurements of evapotranspiration from TERN flux tower data provides the capacity to evaluate and improve the estimation of evapotranspiration in GRASP. Model changes include incorporation of satellite-derived fractional ground cover index for green and total cover in the understorey and persistent green for foliage projected cover to further improve the modelling by constraining estimates of evapotranspiration components. Combining field data with remotely sensed data and a global optimiser in an automated system provides the ability to inform model parameterisation and evaluation. Improving evapotranspiration modelling improves the soil water balance, pasture growth, tree-grass competition and safe carrying capacity, where animal numbers are matched to available pasture. Implications for these model changes and evaluation are significant, as this improves our capacity to model grazing land management issues such as runoff, export of sediment to the reef and sustainable long-term carrying capacity. Key learnings from the optimisation experiments revealed where the model needed improvements, along with careful consideration of trade-offs in regard to variable weighting when optimising multiple measured data groups (such as soil moisture, evapotranspiration and green cover). Model improvements removed the 'spikes' in daily evapotranspiration, compared well to measured data and reduced estimated tree transpiration. Daily estimates of surface soil moisture from remote sensing platforms can be used in model calibration but first require model processes and parameterisation to be appropriate at daily time steps. Calibration of evapotranspiration at a daily time step has not been tested before with GRASP due to the lack of high quality daily data sets, especially from mixed tree and grass systems. These results demonstrate the improvements in GRASP for estimating daily and monthly evapotranspiration in mixed tree and grass systems
Association of MUTYH and colorectal cancer
Mutations in the MUTYH gene have been reported to be associated with increased risk of developing colorectal cancer. In this study, we confirmed this association using original data on 928 colorectal cancer cases and 845 healthy controls from Scotland. We then conducted a meta-analysis from published data on the association between mutations at MUTYH and colorectal cancer risk. We show for the first time a small but significant mono-allelic effect with a genotype relative risk (GRR) of 1.27 (95% confidence interval (CI): 1.01–1.61), and confirm and give a more precise estimate of the strong bi-allelic effect with an estimated GRR of 117 (95% CI: 74–184). This study underscores the need for large sample sizes in order to identify small gene effects when the disease allele frequency is low
Survival of MUTYH-Associated Polyposis Patients With Colorectal Cancer and Matched Control Colorectal Cancer Patients
Background: MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior and patient survival, we compared survival between patients with MUTYH-associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population.
Method:s In this retrospective multicenter cohort study from Europe, 147 patients with MUTYH-associated polyposis colorectal cancer were compared with 272 population-based control patients with colorectal cancer who were matched for country, age at diagnosis, year of diagnosis, stage, and subsite of colorectal cancer. Kaplan–Meier survival and Cox regression analyses were used to compare survival between patients with MUTYH-associated polyposis colorectal cancer and control patients with colorectal cancer. All statistical tests were two-sided.
Results: Five-year survival for patients with MUTYH-associated polyposis colorectal cancer was 78% (95% confidence interval [CI] = 70% to 84%) and for control patients was 63% (95% CI = 56% to 69%) (log-rank test, P = .002). After adjustment for differences in age, stage, sex, subsite, country, and year of diagnosis, survival remained better for MUTYH-associated polyposis colorectal cancer patients than for control patients (hazard ratio of death = 0.48, 95% CI = 0.32 to 0.72).
Conclusions: In a European study cohort, we found statistically significantly better survival for patients with MUTYH-associated polyposis colorectal cancer than for matched control patients with colorectal cancer
Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer
Dynamics of cancer cell subpopulations in primary and metastatic colorectal tumors
Intratumor heterogeneity—heterogeneity of cancer cells within a single tumor—is considered one of the most problematic factors of treatment. Genetic heterogeneity, such as in somatic mutations and chromosome aberrations, is a common characteristic of human solid tumors and is probably the basis of biological heterogeneity. Using mutations in APC, TP53 and KRAS as markers to identify distinct colorectal cancer subpopulations, we analyzed a total of 42 primary colorectal cancer tissues and six paired liver metastases with multipoint microsampling, which enabled analysis of mutation patterns and allelic imbalances with a resolution of 0.01 mm2 (about 200 cells). There was usually more than one subpopulation in each primary tumor. Only two of 15 (13.3%) cases with three gene mutations and eight of 27 (29.6%) cases with two gene mutations had a single subpopulation. Cells with mutations in all of the examined genes usually constituted the major population. Multipoint microsampling of six primary and metastatic tumor pairs revealed that the majority of discrepancies in mutation patterns found with the bulk tissue analysis were due to loss of subpopulations in the metastatic tissues. In addition, multipoint microsampling uncovered substantial changes in subpopulations that were not detected with bulk tissue analysis. Specifically, the proportion of KRAS mutation-negative subpopulations increased in the metastatic tumors of four cases. Because KRAS mutation status is linked to cetuximab/panitumumab efficacy, subpopulation dynamics could lead to differences in response to cetuximab/panitumumab in primary versus metastatic tumors
Most Patients with Colorectal Tumors at Young Age Do Not Visit a Cancer Genetics Clinic
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70595.pdf (publisher's version ) (Open Access)PURPOSE: This study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer and to search for determinants of variation in this referral process. METHODS: Patients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome, hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital setting were explored with logistic regression modeling. RESULTS: Thirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic. CONCLUSION: The referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in nonteaching hospitals
Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients
<p>Abstract</p> <p>Background</p> <p>Patients with hereditary non-poliposys colorectal cancer (HNPCC) have better prognosis than sporadic colorectal cancer (CRC). Aim of our retrospective study was to compare the overall survival between sporadic CRC and HNPCC patients.</p> <p>Methods</p> <p>We analyzed a cohort of 40 (25 males and 15 females) HNPCC cases with a hospital consecutive series of 573 (312 males and 261 females) sporadic CRC observed during the period 1970–1993. In 15 HNPCC patients we performed mutational analysis for microsatellite instability. Survival rates were calculated by Kaplan-Meier method and compared with log rank test.</p> <p>Results</p> <p>The median age at diagnosis of the primary CRC was 46.8 years in the HNPCC series versus 61 years in sporadic CRC group. In HNPCC group 85% had a right cancer location, vs. 57% in the sporadic cancer group. In the sporadic cancer group 61.6% were early-stages cancer (Dukes' A and B) vs. 70% in the HNPCC group (p = ns). The crude 5-years cumulative survival after the primary CRC was 94.2% in HNPCC patients vs. 75.3% in sporadic cancer patients (p < 0.0001).</p> <p>Conclusion</p> <p>Our results show that overall survival of colorectal cancer in patients with HNPCC is better than sporadic CRC patients. The different outcome probably relates to the specific tumorigenesis involving DNA mismatch repair dysfunction.</p
Patients with an unexplained microsatellite instable tumour have a low risk of familial cancer
The cancer risk is unknown for those families in which a microsatellite instable tumour is neither explained by MLH1 promoter methylation nor by a germline mutation in a mismatch repair (MMR) gene. Such information is essential for genetic counselling. Families suspected of Lynch syndrome (n=614) were analysed for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared with those of 18 families with an unexplained microsatellite instable tumour. The mean age at diagnosis of the index patients in both groups was comparable at 44 years. Immunohistochemistry confirmed the loss of an MMR protein. Together this suggests germline inactivation of a known gene. The Amsterdam II criteria were fulfilled in 50/75 families (66%) that carried a germline mutation in an MMR gene and in only 2/18 families (11%) with an unexplained microsatellite instable tumour (P<0.0001). Current diagnostic strategies can detect almost all highly penetrant MMR gene mutations. Patients with an as yet unexplained microsatellite instable tumour likely carry a different type of mutation that confers a lower risk of cancer for relatives
Electronic reminders for pathologists promote recognition of patients at risk for Lynch syndrome: cluster-randomised controlled trial
We investigated success factors for the introduction of a guideline on recognition of Lynch syndrome in patients recently diagnosed with colorectal cancer (CRC) below age 50 or a second CRC below age 70. Pathologists were asked to start microsatellite instability (MSI) testing and report to surgeons with the advice to consider genetic counselling when MSI test or family history was positive. A multicentre cluster-randomised controlled trial (ClinicalTrials.gov, number NCT00141466) was performed in 12 pathology laboratories (clusters), serving 29 community hospitals. All received an introduction to the new guideline. In the intervention group, surgeons received education and tumour test result reminders; pathologists were provided with inclusion criteria cards, an electronic patient inclusion reminder system and feedback on inclusion. Two hundred sixty-six CRC patients were eligible for recognition as at risk for Lynch syndrome. The actual recognition was 18% more successful in the intervention as compared to the control arm (77% (120 of 156) compared to 59% (65 of 110)), with an adjusted odds ratio (OR) = 2.8 (95% confidence interval (CI) 1.1–7.0). The electronic reminder system for pathologists was most strongly associated with recognition of high-risk patients, OR = 4.2 (95% CI 1.7–10.1). An electronic reminder system for pathologists appeared effective for adherence to a new complex guideline and will enhance the recognition of Lynch syndrome
Evidence for classification of c.1852_1853AA>GC in MLH1 as a neutral variant for Lynch syndrome
Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.Generalitat Valenciana in Spain (AP140/08) and the Biomedical Research Foundation from the Hospital of Elche, Spain (FIBElx0902). Conselleria de Educació (Generalitat Valenciana); Fundacion Juan Peran-Pikolinos; Fundacion Carolina-BBVA and Fondo Investigación Sanitaria (FI07/00303). Instituto de Salud Carlos III (INT09/208)
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