Shifts in timing and duration of breeding for 73 boreal bird species over four decades

Breeding timed to match optimal resource abundance is vital for the successful reproduction of species, and breeding is therefore sensitive to environmental cues. As the timing of breeding shifts with a changing climate, this may not only affect the onset of breeding but also its termination, and thus the length of the breeding period. We use an extensive dataset of over 820K nesting records of 73 bird species across the boreal region in Finland to probe for changes in the beginning, end, and duration of the breeding period over four decades (1975 to 2017). We uncover a general advance of breeding with a strong phylogenetic signal but no systematic variation over space. Additionally, 31% of species contracted their breeding period in at least one bioclimatic zone, as the end of the breeding period advanced more than the beginning. We did not detect a statistical difference in phenological responses of species with combinations of different migratory strategy or number of broods. Nonetheless, we find systematic differences in species responses, as the contraction in the breeding period was found almost exclusively in resident and short-distance migrating species, which generally breed early in the season. Overall, changes in the timing and duration of reproduction may potentially lead to more broods co-occurring in the early breeding season-a critical time for species' reproductive success. Our findings highlight the importance of quantifying phenological change across species and over the entire season to reveal shifts in the community-level distribution of bird reproduction.Peer reviewe

Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury

Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1-365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions

Shifts in timing and duration of breeding for 73 boreal bird species over four decades

Breeding timed to match optimal resource abundance is vital for the successful reproduction of species, and breeding is therefore sensitive to environmental cues. As the timing of breeding shifts with a changing climate, this may not only affect the onset of breeding but also its termination, and thus the length of the breeding period. We use an extensive dataset of over 820K nesting records of 73 bird species across the boreal region in Finland to probe for changes in the beginning, end, and duration of the breeding period over four decades (1975 to 2017). We uncover a general advance of breeding with a strong phylogenetic signal but no systematic variation over space. Additionally, 31% of species contracted their breeding period in at least one bioclimatic zone, as the end of the breeding period advanced more than the beginning. We did not detect a statistical difference in phenological responses of species with combinations of different migratory strategy or number of broods. Nonetheless, we find systematic differences in species responses, as the contraction in the breeding period was found almost exclusively in resident and short-distance migrating species, which generally breed early in the season. Overall, changes in the timing and duration of reproduction may potentially lead to more broods co-occurring in the early breeding season—a critical time for species’ reproductive success. Our findings highlight the importance of quantifying phenological change across species and over the entire season to reveal shifts in the community-level distribution of bird reproduction

Variability in the CIITA gene interacts with HLA in multiple sclerosis

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.This work was supported by grants from the Juvenile Diabetes Research Foundation International (2-2000-570 and 1-2001-873), the Swedish Research Council, Swedish Diabetes Foundation, Swedish Child Diabetes Foundation, The Swedish association of persons with neurological disabilities (Neurologiskt Handikappades Riksforbund, NHR), Novo Nordisk Foundation, Magnus Bergvalls Foundation, Neuropromise (LSHM-CT-2005-018637) and the International Multiple Sclerosis Genetics Consortium (IMSGC)Publishe

Shifts in timing and duration of breeding for 73 boreal bird species over four decades

Breeding timed to match optimal resource abundance is vital for the successful reproduction of species, and breeding is therefore sensitive to environmental cues. As the timing of breeding shifts with a changing climate, this may not only affect the onset of breeding but also its termination, and thus the length of the breeding period. We use an extensive dataset of over 820K nesting records of 73 bird species across the boreal region in Finland to probe for changes in the beginning, end, and duration of the breeding period over four decades (1975 to 2017). We uncover a general advance of breeding with a strong phylogenetic signal but no systematic variation over space. Additionally, 31% of species contracted their breeding period in at least one bioclimatic zone, as the end of the breeding period advanced more than the beginning. We did not detect a statistical difference in phenological responses of species with combinations of different migratory strategy or number of broods. Nonetheless, we find systematic differences in species responses, as the contraction in the breeding period was found almost exclusively in resident and short-distance migrating species, which generally breed early in the season. Overall, changes in the timing and duration of reproduction may potentially lead to more broods co-occurring in the early breeding season-a critical time for species' reproductive success. Our findings highlight the importance of quantifying phenological change across species and over the entire season to reveal shifts in the community-level distribution of bird reproduction.Peer reviewe

Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.Juvenile Diabetes Research Foundation International (2-2000-570) and (1-2001-873The Swedish Research CouncilSvenska Diabetes FondenBarndiabetes FondenNovo Nordisk FoundationMagnus Bergvalls FoundationNeuropromise (LSHM-CT-2005-018637)NIH grant DK-17047Swedish Brain Power initiativeGun and Bertil Stohne’s Foundation,Foundation for Old ServantsAlzheimer FoundationLIONS Foundation for Research of Age Related DisordersAFA foundationSöderberg FoundationKnut and Alice Wallenbergs FoundationManuscrip

Parallel imaging: is GRAPPA a useful acquisition tool for MR imaging intended for volumetric brain analysis?

<p>Abstract</p> <p>Background</p> <p>The work presented here investigates parallel imaging applied to T1-weighted high resolution imaging for use in longitudinal volumetric clinical studies involving Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) patients. This was in an effort to shorten acquisition times to minimise the risk of motion artefacts caused by patient discomfort and disorientation. The principle question is, "Can parallel imaging be used to acquire images at 1.5 T of sufficient quality to allow volumetric analysis of patient brains?"</p> <p>Methods</p> <p>Optimisation studies were performed on a young healthy volunteer and the selected protocol (including the use of two different parallel imaging acceleration factors) was then tested on a cohort of 15 elderly volunteers including MCI and AD patients. In addition to automatic brain segmentation, hippocampus volumes were manually outlined and measured in all patients. The 15 patients were scanned on a second occasion approximately one week later using the same protocol and evaluated in the same manner to test repeatability of measurement using images acquired with the GRAPPA parallel imaging technique applied to the MPRAGE sequence.</p> <p>Results</p> <p>Intraclass correlation tests show that almost perfect agreement between repeated measurements of both segmented brain parenchyma fraction and regional measurement of hippocampi. The protocol is suitable for both global and regional volumetric measurement dementia patients.</p> <p>Conclusion</p> <p>In summary, these results indicate that parallel imaging can be used without detrimental effect to brain tissue segmentation and volumetric measurement and should be considered for both clinical and research studies where longitudinal measurements of brain tissue volumes are of interest.</p

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Projektering av ett småhus samt ekonomisk jämförelse av värmesystem

Design of a house requires knowledge of both technology and economics. Heating and ventilation shall be designed, costs are calculated and estimated and requirements must be fulfilled. Which heating system is to be elected is also a difficult choice, especially with rising energy prices as a factor. The choice of energy system is not always given, because it depends on several factors. Below is a comparison between district heating, geothermal heat pump and electric boiler from an economic standpoint. In a previous report appears district heating and geothermal heat pump as the best options. The analysis in this work, district heating appears as the best system for projected house with an energy consumption of 10MWh. An analysis is made by varying some factors in the economic calculations. With half the economic useful life of the systems, the geothermal heat pump is considerably more expensive than the electric boiler, which should be considered if new efficient heating system will enter the market. When energy consumption is reduced to 5MWh, electric boiler is cheaper than geothermal heat pump, set to annual annuities. The conclusion is that the district heating is the best option for an energy consumption of 10 MWh, followed closely by geothermal heating. But energy consumption is very great influence which we ought to look out for, especially in the future with more energy-efficient building. This can get results to look different