Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional ...or national registries.
Data were obtained for children and/or adults with Type 1 diabetes from the following countries (or regions): Western Australia, Austria, Denmark, England, Champagne-Ardenne (France), Germany, Epirus, Thessaly and Thessaloniki (Greece), Galway (Ireland), several Italian regions, Latvia, Rotterdam (The Netherlands), Otago (New Zealand), Norway, Northern Ireland, Scotland, Sweden, Volyn (Ukraine), USA and Wales) from population or clinic-based registries. The sample size with available data varied from 355 to 173 880. Proportions with HbA1c < 58 mmol/mol (< 7.5%) and ≥ 75 mmol/mol (≥ 9.0%) were compared by age and sex.
Data were available for 324 501 people. The proportions with HbA1c 58 mmol/mol (< 7.5%) varied from 15.7% to 46.4% among 44 058 people aged < 15 years, from 8.9% to 49.5% among 50 766 people aged 15-24 years and from 20.5% to 53.6% among 229 677 people aged ≥ 25 years. Sex differences in glycaemic control were small. Proportions of people using insulin pumps varied between the 12 sources with data available.
These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.
Data availability and temporal resolution make it challenging to unravel the anatomy (duration and temporal phasing) of the Last Glacial abrupt climate changes. Here, we address these limitations by ...investigating the anatomy of abrupt changes using sub-decadal-scale records from Greenland ice cores. We highlight the absence of a systematic pattern in the anatomy of abrupt changes as recorded in different ice parameters. This diversity in the sequence of changes seen in ice-core data is also observed in climate parameters derived from numerical simulations which exhibit self-sustained abrupt variability arising from internal atmosphere-ice-ocean interactions. Our analysis of two ice cores shows that the diversity of abrupt warming transitions represents variability inherent to the climate system and not archive-specific noise. Our results hint that during these abrupt events, it may not be possible to infer statistically-robust leads and lags between the different components of the climate system because of their tight coupling.
Mutations in the LKB1 (also known as
) tumor suppressor are the third most frequent genetic alteration in non-small cell lung cancer (NSCLC).
encodes a serine/threonine kinase that directly ...phosphorylates and activates 14 AMPK family kinases ("AMPKRs"). The function of many of the AMPKRs remains obscure, and which are most critical to the tumor-suppressive function of LKB1 remains unknown. Here, we combine CRISPR and genetic analysis of the AMPKR family in NSCLC cell lines and mouse models, revealing a surprising critical role for the SIK subfamily. Conditional genetic loss of
revealed increased tumor growth in mouse models of
-dependent lung cancer, which was further enhanced by loss of the related kinase
. As most known substrates of the SIKs control transcription, gene-expression analysis was performed, revealing upregulation of AP1 and IL6 signaling in common between LKB1- and SIK1/3-deficient tumors. The SIK substrate CRTC2 was required for this effect, as well as for proliferation benefits from SIK loss. SIGNIFICANCE: The tumor suppressor
encodes a serine/threonine kinase frequently inactivated in NSCLC. LKB1 activates 14 downstream kinases in the AMPK family controlling growth and metabolism, although which kinases are critical for LKB1 tumor-suppressor function has remained an enigma. Here we unexpectedly found that two understudied kinases, SIK1 and SIK3, are critical targets in lung cancer.
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Abstract
Introduction/background
Early rule in/rule out algorithms using high sensitivity cardiac troponin T (hs-cTnT) have improved the evaluation for acute coronary syndrome (ACS) and facilitated ...the care of chest pain patients in the emergency department (ED). It is still unknown whether risk factors and comorbidities provide additional diagnostic information for ACS to one-hour hs-cTnT dynamics in the ED.
Purpose
To evaluate whether cardiovascular risk factors and comorbidities are associated with ACS in chest pain patients with elevated and normal initial hs-cTnT, and with and without early dynamic change.
Methods
48,283 unique patients with chest pain and a measured hs-cTnT were identified at 4 university hospitals during 2013-2016 where a one-hour algorithm was implemented during the study period. Among these, 7903 patients had two hs-cTnT measurements obtained within 105 minutes. Clinical information was cross-linked to national registers to obtain previous diagnoses, outcomes and prescriptions. Early dynamics of hs-cTnT was defined as a change by 3ng/l or more if the first hs-cTnT was at or below 14 ng/l, or otherwise a change by more than 20% if the first hs-cTnT was above 14ng/l. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between risk factors and ACS in subgroups by different hs-cTnT levels and with or without dynamic change.
Results
516 out of 39777 (1.3%) patients with normal and 1999 out of 8506 (23.5%) with elevated hs-cTnT levels were diagnosed with ACS. In patients with normal initial hs-cTnT 55 out of 5936 (0.9%) without and 44 out of 186 patients (23.7%) with dynamic change were diagnosed with ACS. In patients with elevated hs-cTnT 196 out of 1464 (13.4%) without and 202 out of 317 patients (63.7%) with dynamic change had ACS. In patients with normal hs-cTnT, hypertension (OR 3.24, 95% CI, 2.72-3.87), hyperlipidaemia (OR 3.21, 95% CI 2.67-3.85), diabetes (OR 3.46, 95% CI, 2.81-4.27) and atherosclerotic cardiovascular disease (ASCVD) (OR 2.92, 95% CI 3.24-4.70) were associated with increased risk for ACS (figure 1), whereas the opposite or no association for ACS was shown for these conditions when the initial hs-TnT was elevated. Among patients with normal initial hs-cTnT, hypertension (OR 2.52, 95% CI, 1.47-4.30) and hyperlipidaemia (OR 2.63. 95% CI, 1.51-4.57) were only associated with ACS in patients without early dynamic change (p-value for interaction <0.001 and p=0.02 respectively) whereas diabetes and ASCVD were associated with ACS irrespective of early dynamics (figure 2).
Conclusion
Cardiovascular risk factors and comorbidities have different diagnostic value for ACS depending on whether the initial hs-cTnT level is elevated and whether an early dynamic change in hs-cTnT is present. Further investigations of combined comorbidities, hs-cTnT levels and its correlation with ACS could refine risk stratifying algorithms among these patients.Figure 1troponin - ACSFigure 2troponin, dynamics - ACS
Dehydrins (DHNs) compose a family of intrinsically unstructured proteins that have high water solubility and accumulate during late seed development, low temperature or water deficit conditions, and ...are thought to play a protective role in freezing and drought tolerance in plants. Twelve Dhn genes were previously described in the barley genome. Here, we report an additional member of this multigene family, Dhn13. The Dhn13 gene is located in chromosome 4 near marker MWG634 and encodes a 107-amino acid KS-type DHN. Semi-quantitative reverse transcriptase PCR data indicated that Dhn13 is constitutively expressed in seedling tissues and embryos of developing seeds. Microarray data were consistent with these results and showed a considerable increase of Dhn13 transcripts when plants were subjected to chilling and freezing temperatures. The highest transcript levels where observed in anthers. The presence of ABRE, MYC, DRE, and POLLEN1LELAT52 regulatory elements in the putative Dhn13 promoter region is in agreement with expression data.
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