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Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Climate or Land Use?
(2015)
This study intends to contribute to the ongoing discussion on whether land use and land cover changes (LULC) or climate trends have the major influence on the observed increase of flood magnitudes in the Sahel. A simulation-based approach is used for attributing the observed trends to the postulated drivers. For this purpose, the ecohydrological model SWIM (Soil and Water Integrated Model) with a new, dynamic LULC module was set up for the Sahelian part of the Niger River until Niamey, including the main tributaries Sirba and Goroul. The model was driven with observed, reanalyzed climate and LULC data for the years 1950-2009. In order to quantify the shares of influence, one simulation was carried out with constant land cover as of 1950, and one including LULC. As quantitative measure, the gradients of the simulated trends were compared to the observed trend. The modeling studies showed that for the Sirba River only the simulation which included LULC was able to reproduce the observed trend. The simulation without LULC showed a positive trend for flood magnitudes, but underestimated the trend significantly. For the Goroul River and the local flood of the Niger River at Niamey, the simulations were only partly able to reproduce the observed trend. In conclusion, the new LULC module enabled some first quantitative insights into the relative influence of LULC and climatic changes. For the Sirba catchment, the results imply that LULC and climatic changes contribute in roughly equal shares to the observed increase in flooding. For the other parts of the subcatchment, the results are less clear but show, that climatic changes and LULC are drivers for the flood increase; however their shares cannot be quantified. Based on these modeling results, we argue for a two-pillar adaptation strategy to reduce current and future flood risk: Flood mitigation for reducing LULC-induced flood increase, and flood adaptation for a general reduction of flood vulnerability.
Climate or land use?
(2017)
This study intends to contribute to the ongoing discussion on whether land use and land cover changes (LULC) or climate trends have the major influence on the observed increase of flood magnitudes in the Sahel. A simulation-based approach is used for attributing the observed trends to the postulated drivers. For this purpose, the ecohydrological model SWIM (Soil and Water Integrated Model) with a new, dynamic LULC module was set up for the Sahelian part of the Niger River until Niamey, including the main tributaries Sirba and Goroul. The model was driven with observed, reanalyzed climate and LULC data for the years 1950–2009. In order to quantify the shares of influence, one simulation was carried out with constant land cover as of 1950, and one including LULC. As quantitative measure, the gradients of the simulated trends were compared to the observed trend. The modeling studies showed that for the Sirba River only the simulation which included LULC was able to reproduce the observed trend. The simulation without LULC showed a positive trend for flood magnitudes, but underestimated the trend significantly. For the Goroul River and the local flood of the Niger River at Niamey, the simulations were only partly able to reproduce the observed trend. In conclusion, the new LULC module enabled some first quantitative insights into the relative influence of LULC and climatic changes. For the Sirba catchment, the results imply that LULC and climatic changes contribute in roughly equal shares to the observed increase in flooding. For the other parts of the subcatchment, the results are less clear but show, that climatic changes and LULC are drivers for the flood increase; however their shares cannot be quantified. Based on these modeling results, we argue for a two-pillar adaptation strategy to reduce current and future flood risk: Flood mitigation for reducing LULC-induced flood increase, and flood adaptation for a general reduction of flood vulnerability.
All-in-One "Schizophrenic" self-assembly of orthogonally tuned thermoresponsive diblock copolymers
(2019)
Smart, fully orthogonal switching was realized in a highly biocompatible diblock copolymer system with variable trigger-induced aqueous self-assembly. The polymers are composed of nonionic and zwitterionic blocks featuring lower and upper critical solution temperatures (LCSTs and UCSTs). In the system investigated, diblock copolymers from poly(N-isopropyl methacrylamide) (PNIPMAM) and a poly(sulfobetaine methacrylamide), systematic variation of the molar mass of the latter block allowed for shifting the UCST of the latter above the LCST of the PNIPMAM block in a salt-free condition. Thus, successive thermal switching results in "schizophrenic" micellization, in which the roles of the hydrophobic core block and the hydrophilic shell block are interchanged depending on the temperature. Furthermore, by virtue of the strong electrolyte-sensitivity of the zwitterionic polysulfobetaine block, we succeeded to shift its UCST below the LCST of the PNIPMAM block by adding small amounts of an electrolyte, thus inverting the pathway of switching. This superimposed orthogonal switching by electrolyte addition enabled us to control the switching scenarios between the two types of micelles (i) via an insoluble state, if the LCST-type cloud point is below the UCST-type cloud point, which is the case at low salt concentrations or (ii) via a molecularly dissolved state, if the LCST-type cloud point is above the UCST-type cloud point, which is the case at high salt concentrations. Systematic variation of the block lengths allowed for verifying the anticipated behavior and identifying the molecular architecture needed. The versatile and tunable self-assembly offers manifold opportunities, for example, for smart emulsifiers or for sophisticated carrier systems.
Polymeric electrophosphorescent LEDs with internal quantum efficiencies approaching unity have been fabricated. Such performance levels are previously unknown for OLEDs. The key to this success is redox chemically doped oxetane- crosslinkable hole-transporting layers with multilayer capability (see figure). They improve hole injection and act as electron-blocking layers, without the need to include exciton-or hole-blocking layers
Land-use intensification is a key driver of biodiversity change. However, little is known about how it alters relationships between the diversities of different taxonomic groups, which are often correlated due to shared environmental drivers and trophic interactions. Using data from 150 grassland sites, we examined how land-use intensification (increased fertilization, higher livestock densities, and increased mowing frequency) altered correlations between the species richness of 15 plant, invertebrate, and vertebrate taxa. We found that 54% of pairwise correlations between taxonomic groups were significant and positive among all grasslands, while only one was negative. Higher land-use intensity substantially weakened these correlations(35% decrease in rand 43% fewer significant pairwise correlations at high intensity), a pattern which may emerge as a result of biodiversity declines and the breakdown of specialized relationships in these conditions. Nevertheless, some groups (Coleoptera, Heteroptera, Hymenoptera and Orthoptera) were consistently correlated with multidiversity, an aggregate measure of total biodiversity comprised of the standardized diversities of multiple taxa, at both high and lowland-use intensity. The form of intensification was also important; increased fertilization and mowing frequency typically weakened plant-plant and plant-primary consumer correlations, whereas grazing intensification did not. This may reflect decreased habitat heterogeneity under mowing and fertilization and increased habitat heterogeneity under grazing. While these results urge caution in using certain taxonomic groups to monitor impacts of agricultural management on biodiversity, they also suggest that the diversities of some groups are reasonably robust indicators of total biodiversity across a range of conditions.
DrDimont: explainable drug response prediction from differential analysis of multi-omics networks
(2022)
Motivation:
While it has been well established that drugs affect and help patients differently, personalized drug response predictions remain challenging.
Solutions based on single omics measurements have been proposed, and networks provide means to incorporate molecular interactions into reasoning.
However, how to integrate the wealth of information contained in multiple omics layers still poses a complex problem.
Results:
We present DrDimont, Drug response prediction from Differential analysis of multi-omics networks.
It allows for comparative conclusions between two conditions and translates them into differential drug response predictions.
DrDimont focuses on molecular interactions.
It establishes condition-specific networks from correlation within an omics layer that are then reduced and combined into heterogeneous, multi-omics molecular networks. A novel semi-local, path-based integration step ensures integrative conclusions. Differential predictions are derived from comparing the condition-specific integrated networks.
DrDimont's predictions are explainable, i.e. molecular differences that are the source of high differential drug scores can be retrieved. We predict differential drug response in breast cancer using transcriptomics, proteomics, phosphosite and metabolomics measurements and contrast estrogen receptor positive and receptor negative patients. DrDimont performs better than drug prediction based on differential protein expression or PageRank when evaluating it on ground truth data from cancer cell lines. We find proteomic and phosphosite layers to carry most information for distinguishing drug response.