Oncologic outcomes of screen-detected and non-screen-detected T1 colorectal cancers

Background The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program. Methods Data from T1 CRC patients diagnosed between 2014 and 2017 were collected from 12 hospitals in the Netherlands. The presence of lymph node metastasis (LNM) at diagnosis was compared between screen-detected and non-screen-detected patients using multivariable logistic regression. Cox proportional hazard regression was used to analyze differences in the time to recurrence (TTR), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival. Additionally, the performance of conventional risk factors for LNM was evaluated across the groups. Results 1803 patients were included (1114 [62%] screendetected), with median follow-up of 51 months (interquartile range 30). The proportion of LNM did not significantly differ between screen- and non-screen-detected patients (12.6% vs. 8.9%; odds ratio 1.41; 95%CI 0.89-2.23); a prediction model for LNM performed equally in both groups. The 3- and 5-year TTR, MFS, and CSS were similar for patients within and outside the screening program. However, overall survival was significantly longer in screen-detected T1 CRC patients (adjusted hazard ratio 0.51; 95%CI 0.38- 0.68). Conclusions Screen-detected and non-screen-detected T1 CRCs have similar stage distributions and oncologic outcomes and can therefore be treated equally. However, screen-detected T1 CRC patients exhibit a lower rate of non-CRC-related mortality, resulting in longer overall survival

Does Size Matter? The Productivity of Government: Expenditures and the Size of States: Evidence from India

Some politicians argue for the splitting and combining of states to increase government productivity, but there is a dearth of empirical evidence on the optimal size of a state. Using data from Indian states, I test a model of the optimal size of the state. I find that size and preference heterogeneity do not significantly affect the productivity of a state government. However, when states are split up, the productivity of the root state's government is negatively affected. This suggests that there may be a readjustment phase after state reorganisation that brings about this negative effect. It is important to consider this effect when redrawing state borders

The conformation of the idopyranose ring revisited: How subtle O-substituent induced changes can be deduced from vicinal H-1-NMR coupling constants

Contains fulltext : 225082.pdf (postprint version ) (Open Access

The conformation of the idopyranose ring revisited: How subtle O-substituent induced changes can be deduced from vicinal 1H-NMR coupling constants

The idopyranose ring plays a pivotal role in the conformational, dynamical, and intermolecular binding aspects of glycosaminoglycans like heparin and dermatan sulfate and it was early on assigned a role in the Sugar Code governing biological recognition processes. There is consensus that next to the two canonical 1C4 and 4C1 chair conformations, the conformational space accessible to the idopyranose ring entails a 2SO skew-boat conformation, but the equilibrium between these three ring puckers has evaded satisfactory quantification. In this study a meta-analysis of X-ray solid-state data and vicinal NMR coupling constants is presented, based on the Truncated Fourier Puckering (TFP) formalism and the generalized Karplus (CAGPLUS) equation. This approach yields a model-free, granular and consistent reckoning of 159 idopyranose solution puckering equilibria studied by NMR and allows us to reproduce the involved 636 NMR vicinal couplings with an overall residual RMS(Jobs-Jcalc) of 0.184 Hz. Our analyses show that for all ring systems examined, the idopyranosyl chair conformations take up the same ring pucker irrespective of the ring substituent pattern or a vast variety in experimental conditions. Instead, it is the (skew-)boat conformation that adapts to the substitution pattern of the idopyranose ring or a specific sulfation pattern of neighboring saccharides. All idopyranose rings are involved in conformational equilibria that subsume the aforementioned conformers which turn out to differ only a few kJ/mole in conformational energy. Thus, the plasticity and flexibility of idopyranose remains intact under practically all circumstances and, as the glycosidic linkages in heparin are considered to be relatively stiff, the iduronic moiety functions as the linchpin of heparin flexibility thereby being rather a “space(r)” than a “letter” in the alleged Sugar Code alphabet

Transient scenarios for robust climate change adaptation illustrated for water manegement in the Netherlands

Climate scenarios are used to explore impacts of possible future climates and to assess the robustness of adaptation actions across a range of futures. Time-dependent climate scenarios are commonly used in mitigation studies. However, despite the dynamic nature of adaptation, most scenarios for local or regional decision making on climate adaptation are static 'endpoint' projections. This paper describes the development and use of transient (time-dependent) scenarios by means of a case on water management in the Netherlands. Relevant boundary conditions (sea level, precipitation and evaporation) were constructed by generating an ensemble of synthetic time-series with a rainfall generator and a transient delta change method. Climate change impacted river flows were then generated with a hydrological simulation model for the Rhine basin. The transient scenarios were applied in model simulations and game experiments. We argue that there are at least three important assets of using transient scenarios for supporting robust climate adaptation: (1) raise awareness about (a) the implications of climate variability and climate change for decision making and (b) the difficulty of finding proof of climate change in relevant variables for water management; (2) assessment of when to adapt by identifying adaptation tipping points which can then be used to explore adaptation pathways, and (3) identification of triggers for climate adaptation

5,10-Methenyl-5,6,7,8-tetrahydromethanopterin, a One-Carbon Carrier in the Process of Methanogenesis

5,10-Methenyl-5,6,7,8-tetrahydromethanopterin was isolated from Methanobacterium thermoautotrophicum. The structure of this compound was elucidated by various two-dimensional nuclear magnetic resonance techniques and confirmed by fast atom bombardment mass spectrometry. The structure of 5,10-methenyl-5,6,7,8-tetrahydromethanopterin shows one additional carbon atom as compared to the parent compound methanopterin. This additional carbon atom is rapidly labeled in vivo by 13C02. It is shown that 5,10- methenyl-5,6,7,8-tetrahydromethanopterin is a physiologically active one-carbon carrier at the formyl level of oxidation in the methanogenic pathway from C02

The conformation of the idopyranose ring revisited: How subtle O-substituent induced changes can be deduced from vicinal 1H-NMR coupling constants

The idopyranose ring plays a pivotal role in the conformational, dynamical, and intermolecular binding aspects of glycosaminoglycans like heparin and dermatan sulfate and it was early on assigned a role in the Sugar Code governing biological recognition processes. There is consensus that next to the two canonical 1C4 and 4C1 chair conformations, the conformational space accessible to the idopyranose ring entails a 2SO skew-boat conformation, but the equilibrium between these three ring puckers has evaded satisfactory quantification. In this study a meta-analysis of X-ray solid-state data and vicinal NMR coupling constants is presented, based on the Truncated Fourier Puckering (TFP) formalism and the generalized Karplus (CAGPLUS) equation. This approach yields a model-free, granular and consistent reckoning of 159 idopyranose solution puckering equilibria studied by NMR and allows us to reproduce the involved 636 NMR vicinal couplings with an overall residual RMS(Jobs-Jcalc) of 0.184 Hz. Our analyses show that for all ring systems examined, the idopyranosyl chair conformations take up the same ring pucker irrespective of the ring substituent pattern or a vast variety in experimental conditions. Instead, it is the (skew-)boat conformation that adapts to the substitution pattern of the idopyranose ring or a specific sulfation pattern of neighboring saccharides. All idopyranose rings are involved in conformational equilibria that subsume the aforementioned conformers which turn out to differ only a few kJ/mole in conformational energy. Thus, the plasticity and flexibility of idopyranose remains intact under practically all circumstances and, as the glycosidic linkages in heparin are considered to be relatively stiff, the iduronic moiety functions as the linchpin of heparin flexibility thereby being rather a “space(r)” than a “letter” in the alleged Sugar Code alphabet