Studies on β-enaminonitriles: Part III-Reaction of β-aminocrotononitrile with unsaturated acid chlorides : Benary revisited

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Studies in catalytic dehydrogenation: Part X-Syntheses of alkylsubstituted spirol[4,6]undecanes and dehydrogenation of 1-ethyl-8,9- benzospiro[4,6]undecane

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SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes

Diabetic kidney disease (DKD) is a topic of increasing concern among clinicians involved in the management of type 2 diabetes mellitus (T2DM). It is a progressive and costly complication associated with increased risk of adverse cardiovascular (CV) and renal outcomes and mortality. Ongoing monitoring of the estimated glomerular filtration (eGFR) rate alongside the urine albumin:creatinine ratio (ACR) is recommended during regular T2DM reviews to enable a prompt DKD diagnosis or to assess disease progression, providing an understanding of adverse risk for each individual. Many people with DKD will progress to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT), typically haemodialysis or kidney transplantation. A range of lifestyle and pharmacological interventions is recommended to help lower CV risk, slow the advancement of DKD and prevent or delay the need for RRT. Emerging evidence concerning sodium-glucose co-transporter-2 inhibitor (SGLT2i) agents suggests a role for these medicines in slowing eGFR decline, enabling regression of albuminuria and reducing progression to ESKD. Improvements in renal end points observed in SGLT2i CV outcome trials (CVOTs) highlighted the possible impact of these agents in the management of DKD. Data from the canagliflozin CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) have since demonstrated the effectiveness of this medicine in reducing the risk of kidney failure and CV events in a population comprising individuals with T2DM and renal disease. CREDENCE was the first SGLT2i study to examine renal outcomes as the primary end point. Real-world studies have reaffirmed these outcomes in routine clinical practice. This article summarises the evidence regarding the use of SGLT2i medicines in slowing the progression of DKD and examines the possible mechanisms underpinning the renoprotective effects of these agents. The relevant national and international guidance for monitoring and treatment of DKD is also highlighted to help clinicians working to support this vulnerable group

Decomposing the spatial and temporal effects of climate on bird populations in northern European mountains

The relationships between species abundance or occurrence versus spatial variation in climate are commonly used in species distribution models to forecast future distributions. Under "space-for-time substitution", the effects of climate variation on species are assumed to be equivalent in both space and time. Two unresolved issues of space-for-time substitution are the time period for species' responses and also the relative contributions of rapid- versus slow reactions in shaping spatial and temporal responses to climate change. To test the assumption of equivalence, we used a new approach of climate decomposition to separate variation in temperature and precipitation in Fennoscandia into spatial, temporal, and spatiotemporal components over a 23-year period (1996-2018). We compiled information on land cover, topography, and six components of climate for 1756 fixed route surveys, and we modeled annual counts of 39 bird species breeding in the mountains of Fennoscandia. Local abundance of breeding birds was associated with the spatial components of climate as expected, but the temporal and spatiotemporal climatic variation from the current and previous breeding seasons were also important. The directions of the effects of the three climate components differed within and among species, suggesting that species can respond both rapidly and slowly to climate variation and that the responses represent different ecological processes. Thus, the assumption of equivalent species' response to spatial and temporal variation in climate was seldom met in our study system. Consequently, for the majority of our species, space-for-time substitution may only be applicable once the slow species' responses to a changing climate have occurred, whereas forecasts for the near future need to accommodate the temporal components of climate variation. However, appropriate forecast horizons for space-for-time substitution are rarely considered and may be difficult to reliably identify. Accurately predicting change is challenging because multiple ecological processes affect species distributions at different temporal scales.Peer reviewe

Integrated population models poorly estimate the demographic contribution of immigration

Estimating the contribution of demographic parameters to changes in population growth is essential for understanding why populations fluctuate. Integrated population models (IPMs) offer a possibility to estimate the contributions of additional demographic parameters, for which no data have been explicitly collected—typically immigration. Such parameters are often subsequently highlighted as important drivers of population growth. Yet, accuracy in estimating their temporal variation, and consequently their contribution to changes in population growth rate, has not been investigated. To quantify the magnitude and cause of potential biases when estimating the contribution of immigration using IPMs, we simulated data (using northern wheatear Oenanthe oenanthe population estimates) from controlled scenarios to examine potential biases and how they depend on IPM parameterization, formulation of priors, the level of temporal variation in immigration and sample size. We also used empirical data on populations with known rates of immigration: Soay sheep Ovis aries and Mauritius kestrel Falco punctatus with zero immigration and grey wolf Canis lupus in Scandinavia with near-zero immigration. IPMs strongly overestimated the contribution of immigration to changes in population growth in scenarios when immigration was simulated with zero temporal variation (proportion of variance attributed to immigration = 63% for the more constrained formulation and real sample size) and in the wild populations, where the true number of immigrants was zero or near-zero (kestrel 19.1%–98.2%, sheep 4.2%–36.1% and wolf 84.0%–99.2%). Although the estimation of the contribution of immigration in the simulation study became more accurate with increasing temporal variation and sample size, it was often not possible to distinguish between an accurate estimation from data with high temporal variation versus an overestimation from data with low temporal variation. Unrealistically, large sample sizes may be required to estimate the contribution of immigration well. To minimize the risk of overestimating the contribution of immigration (or any additional parameter) in IPMs, we recommend to: (a) look for evidence of variation in immigration before investigating its contribution to population growth, (b) simulate and model data for comparison to the real data and (c) use explicit data on immigration when possible

Towards constraints on the SUSY seesaw from flavour-dependent leptogenesis

We systematically investigate constraints on the parameters of the supersymmetric type-I seesaw mechanism from the requirement of successful thermal leptogenesis in the presence of upper bounds on the reheat temperature $T_\mathrm{RH}$ of the early Universe. To this end, we solve the flavour-dependent Boltzmann equations in the MSSM, extended to include reheating. With conservative bounds on $T_\mathrm{RH}$, leading to mildly constrained scenarios for thermal leptogenesis, compatibility with observation can be obtained for extensive new regions of the parameter space, due to flavour-dependent effects. On the other hand, focusing on (normal) hierarchical light and heavy neutrinos, the hypothesis that there is no CP violation associated with the right-handed neutrino sector, and that leptogenesis exclusively arises from the CP-violating phases of the $U_\text{MNS}$ matrix, is only marginally consistent. Taking into account stricter bounds on $T_\mathrm{RH}$ further suggests that (additional) sources of CP violation must arise from the right-handed neutrino sector, further implying stronger constraints for the right-handed neutrino parameters.Comment: 42 pages, 12 figures; final version published in JCAP; numerical results for the efficiency factor can be downloaded from http://www.newphysics.eu/leptogenesis