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Background Poor social health is associated with increased risk of cardiovascular disease (CVD). Recent research suggests that different social health domains should be considered separately as the implications for health and possible interventions may differ. Aim To assess social isolation, low social support and loneliness as predictors of CVD. Methods Secondary analysis of 11,486 community-dwelling, Australians, aged 70 years and over, free of CVD, dementia, or significant physical disability, from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Social isolation, social support (Revised Lubben Social Network Scale), and loneliness were assessed as predictors of CVD using Cox proportional-hazard regression. CVD events included fatal CVD, heart failure hospitalization, myocardial infarction and stroke. Analyses were adjusted for established CVD risk factors. Results Individuals with poor social health were 42 % more likely to develop CVD (p = 0.01) and twice as likely to die from CVD (p = 0.02) over a median 4.5 years follow-up. Interaction effects indicated that poorer social health more strongly predicted CVD in smokers (HR 4.83, p = 0.001, p-interaction = 0.01), major city dwellers (HR 1.94, p < 0.001, p-interaction=0.03), and younger older adults (70-75 years; HR 2.12, p < 0.001, p-interaction = 0.01). Social isolation (HR 1.66, p = 0.04) and low social support (HR 2.05, p = 0.002), but not loneliness (HR 1.4, p = 0.1), predicted incident CVD. All measures of poor social health predicted ischemic stroke (HR 1.73 to 3.16). Conclusions Among healthy older adults, social isolation and low social support may be more important than loneliness as cardiovascular risk factors. Social health domains should be considered in future CVD risk prediction models.

Increasing numbers of patients are presenting worldwide to emergency departments with suspected myocardial infarction. The use of point-of-care troponin assays might enable faster decision-making in this high-risk population and reduce the burden on emergency facilities. Here, we evaluate the diagnostic performance of a point-of-care high-sensitivity troponin I assay. We conducted a prospective cohort study including patients presenting to the emergency department with suspected myocardial infarction from July 2013 to July 2016. A diagnostic algorithm for a high-sensitivity troponin I point-of-care assay was developed in a derivation data set with 669 patients and validated in an additional 610 patients. The derived 0/1 h algorithm for the point-of-care assay consisted of an admission troponin I <4 ng/L and a δ from 0 h to 1 h <3 ng/L for rule out and an admission troponin I ≥90 ng/L or a δ from 0 h to 1 h ≥20 ng/L for rule in of non-ST-elevation myocardial infarction. Application to the validation cohort showed a negative predictive value of 99.7% (95% CI, 98.1%-100.0%) and 48.0% of patients ruled out, whereas 14.6% were ruled in with a positive predictive value of 86.5% (95% CI, 77.6%-92.8%). The diagnostic performance of the point-of-care high-sensitivity assay was highly comparable to guideline-recommended use of a laboratory-based high-sensitivity troponin assay. The clinical application of a 0/1 h diagnostic algorithm based on a high-sensitivity troponin I point-of-care assay is safe, and diagnostic performance is comparable to a laboratory-based high-sensitivity troponin I assay.

In Europe, offshore wind farms have a capacity of 16 GW, with 71% installed at the North Sea. These wind farms represent an additional source of turbulence and may influence the stratification of the marine boundary layer. We present aircraft measurements and simulations showing an impact on temperature and humidity at hub height in the order of 0.5 K and 0.5 g kg−1 even 60 km downwind of a wind farm cluster. We extend these simulations to explore a realistic future scenario, suggesting wakes in potential temperature and water vapor propagating more than 100 km downwind. Such impacts of wind farms are only observed in case of a strong stable stratification at rotor height, allowing wind farms to mix warmer air downward.

Carbon isotope labelling of bioactive molecules is essential for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Aryl carboxylic acids represent an important class of structural motifs ubiquitous in pharmaceutically active molecules and are ideal targets for the installation of a radioactive tag employing isotopically labelled CO 2 . However, direct isotope incorporation via the reported catalytic reductive carboxylation (CRC) of aryl electrophiles relies on excess CO 2 , which is incompatible with carbon-14 isotope incorporation. Furthermore, the application of some CRC reactions for late-stage carboxylation is limited because of the low tolerance of molecular complexity by the catalysts. Herein, we report the development of a practical and affordable Pd-catalysed electrocarboxylation setup. This approach enables the use of near-stoichiometric 14 CO 2 generated from the primary carbon-14 source Ba 14 CO 3 , facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors. The proposed isotope-labelling protocol holds significant promise for immediate impact on drug development programmes. Carbon isotope labelling of bioactive molecules is essential for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Here, the authors propose an electrochemical isotope-labelling protocol which enables the use of near-stoichiometric 14 CO 2 , facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors.

Surface melting on the Greenland Ice Sheet is common up to ∼1400 m elevation and, in extreme melt years, even higher. Water produced on the ice sheet surface collects in lakes and drains over the ice sheet surface via supraglacial streams and through the ice sheet via moulins. Water delivered to the base of the ice sheet can cause uplift and enhanced sliding locally. Here we use ice‐penetrating radar data to observe the effects of significant basal melting coincident with moulins and calculate how much basal melt occurred. We find that more melting has occurred than can be explained by the release of potential energy from the drainage of surface meltwater during one melt season suggesting that these moulins are persistent for multiple years. We find only a few persistent moulins in our study area that drain the equivalent of multiple lakes per year and likely remain active over several years. Our observations indicate that once established, these persistent moulins might be capable of establishing well‐connected meltwater drainage pathways.

Cardiopulmonary arrest is a leading cause of death and disability in the United States that usually occurs in the aged population. Cardiac arrest (CA) induces global ischemia, disrupting global cerebral circulation that results in ischemic brain injury and leads to cognitive impairments in survivors. Ischemia-induced neuronal damage in the hippocampus following CA can result in the impairment of cognitive function including spatial memory. In the present study, we used a model of asphyxial CA (ACA) in nine month old male Fischer 344 rats to investigate cognitive and synaptic deficits following mild global cerebral ischemia. These experiments were performed with the goals of 1) establishing a model of CA in nine month old middle-aged rats; and 2) to test the hypothesis that learning and memory deficits develop following mild global cerebral ischemia in middle-aged rats. To test this hypothesis, spatial memory assays (Barnes circular platform maze and contextual fear conditioning) and field recordings (long-term potentiation and paired-pulse facilitation) were performed. We show that following ACA in nine month old middle-aged rats, there is significant impairment in spatial memory formation, paired-pulse facilitation n dysfunction, and a reduction in the number of non-compromised hippocampal Cornu Ammonis 1 and subiculum neurons. In conclusion, nine month old animals undergoing cardiac arrest have impaired survival, deficits in spatial memory formation, and synaptic dysfunction.

The transition from hunter-gatherer-fisher groups to agrarian societies is arguably the most significant change in human prehistory. In the European plain there is evidence for fully developed agrarian societies by 7,500 cal. yr BP, yet a well-established agrarian society does not appear in the north until 6,000 cal. yr BP for unknown reasons. Here we show a sudden increase in summer temperature at 6,000 cal. yr BP in northern Europe using a well-dated, high resolution record of sea surface temperature (SST) from the Baltic Sea. This temperature rise resulted in hypoxic conditions across the entire Baltic sea as revealed by multiple sedimentary records and supported by marine ecosystem modeling. Comparison with summed probability distributions of radiocarbon dates from archaeological sites indicate that this temperature rise coincided with both the introduction of farming, and a dramatic population increase. The evidence supports the hypothesis that the boundary of farming rapidly extended north at 6,000 cal. yr BP because terrestrial conditions in a previously marginal region improved.

Abstract Background Emergency departments worldwide are increasingly adopting rapid diagnosis of patients with suspected myocardial infarction (MI) based on high-sensitivity troponin. We set out to assess the diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay in a prospective study. Methods In a cohort study including 1800 patients presenting with suspected acute MI, we developed and temporally validated a 0/1 h diagnostic algorithm using the Siemens Atellica IM hs-cTnI assay. The algorithm was established in the first 928 patients and validated in the following 872 patients. Results The derived algorithm consisted of a baseline rule-out of non–ST-segment elevation MI using a cutoff <3 ng/L in patients with symptom onset ≥3 h or an admission troponin I level <6 ng/L with a Δ change of <3 ng/L from 0 h to 1 h. For rule-in, an admission troponin I level ≥120 ng/L or an increase within the first hour ≥12 ng/L was required. Application of the algorithm to the validation cohort showed a negative predictive value of 99.8% (95% CI, 98.7%–100.0%), sensitivity of 99.1% (95% CI, 95.1%–100.0%), and 48.3% of patients ruled out, whereas 15.1% were ruled in with a positive predictive value of 68.0% (95% CI, 59.1%–75.9%) and specificity of 94.4% (95% CI, 92.5%–96.0%). The diagnostic performance was comparable to guideline-recommended application of an established hs-cTnI assay in a rapid 0/1 h strategy. Conclusions The Siemens hs-cTnI assay is well suited for application in rapid diagnostic stratification of patients with suspected MI. Study Registration www.clinicaltrials.gov (NCT02355457)

Background:Multiple organ involvement is a typical feature of vasculitis in general, particularly in ANCA-associated vasculitis (AAV). The alignment of organ involvement to classification criteria has been previously confirmed [1].Objectives:This study aimed to explore differences between GPA and MPA in terms of single organ involvement and especially overlaps in organ manifestations.Methods:We collected data from AAV patients at four tertiary referral centers (Germany and Switzerland) between 2000 and 2022, classification was performed in accordance with the 2022 ACR/EULAR criteria for GPA and MPA. Organ involvement was identified by BVAS entries. Important manifestation, regarding kidney, lung, ear, nose, and throat (ENT), and nervous system were compared between AAV-entities by Pearson’s Chi2-test and their combinations illustrated graphically.Results:The dataset included 358 patients, of whom 168 (46.9%) were females, with a median age of 61 years (25-75 percentile: 50-70). According to the 2022 ACR/EULAR criteria, 203 (58.1%) were classified as GPA, 139 (38.8%) as MPA. Renal involvement was dominant in MPA (84.9%) compared to GPA (68.3%), while pulmonary affection was found in 59.6% in GPA vs. 38.8% in MPA. ENT involvement was present in 50% of all GPA cases but only in 11.5% of MPA cases, with all differences found to be significant (p <.001). Isolated ENT involvement was completely uncommon in MPA (0%), whereas a combination with kidney and lung was documented in 8 cases, exclusively with kidney in 4, with lung in 4 cases, and a combination of nervous, renal, and pulmonary manifestations was documented once. Figure 1 visualizes the widespread distribution and most frequent combinations of organ manifestations in GPA in comparison to MPA. Of note, sole renal affection in MPA was found more frequently (39/139, 28.1%) than its combination with general symptoms (26, 18.7%) or overlapping with pulmonal manifestation (13, 9.4%).Conclusion:In our cohort, GPA exhibits a broader range of organ involvement compared to MPA, where a higher occurrence of single-organ manifestations is observed. The distinctions between GPA and MPA are evident in age, with notable differences in ENT involvement. In contrast to a previous German cohort study in 2016 [2], which reported 97.1% of MPA cases presenting with general symptoms, our current analysis indicates a significant number of cases displaying only kidney involvement without additional symptoms. This divergence may be attributed to the impact of the new ACR/EULAR criteria, leading to the classification of more cases as MPA with limited renal involvement.Figure 1.Organ involvement and overlaps in MPA (left) and GPA (right) in a European cohort (renal affection is highlighted in blue, combinations with a frequency below three are not displayed, resulting in total numbers of 135 for MPA and 203 cases in GPA).REFERENCES:[1] Krämer S, Rauen T, Vogt K, et a. Alignment Between the Novel 2022 ACR/EULAR Classification Criteria for ANCA-associated Vasculitis (AAV), Clinical Diagnosis and Organ Manifestations in a European AAV Cohort - ACR Meeting Abstracts. Arthritis rheumatol. (2023) 75 (supplement 9).[2] Schirmer HJ, Wright, NM, Vontheim R, et al. Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology, Volume 55, Issue 1, January 2016, Pages 71–79.Acknowledgements:NIL.Disclosure of Interests:Stefan Krämer: None declared, Thomas Rauen Vifor, Kristian Vogt: None declared, Theresa Schreibing: None declared, Martin Busch Vifor, Raoul Bergner Vifor, Sebastian Mosberger: None declared, Tobias Schmitt: None declared, Thomas Neumann Vifor.

Summary Trabecular bone score (TBS) seems to provide additive value on BMD to identify individuals with prevalent fractures in T1D. TBS did not significantly differ between T1D patients and healthy controls, but TBS and HbA1c were independently associated with prevalent fractures in T1D. A TBS cutoff <1.42 reflected prevalent fractures with 91.7 % sensitivity and 43.2 % specificity. Introduction Type 1 diabetes (T1D) increases the risk of osteoporotic fractures. TBS was recently proposed as an indirect measure of bone microarchitecture. This study aimed at investigating the TBS in T1D patients and healthy controls. Associations with prevalent fractures were tested. Methods One hundred nineteen T1D patients (59 males, 60 premenopausal females; mean age 43.4 ± 8.9 years) and 68 healthy controls matched for gender, age, and body mass index (BMI) were analyzed. The TBS was calculated in the lumbar region, based on two-dimensional (2D) projections of DXA assessments. Results TBS was 1.357 ± 0.129 in T1D patients and 1.389 ± 0.085 in controls ( p  = 0.075). T1D patients with prevalent fractures ( n  = 24) had a significantly lower TBS than T1D patients without fractures (1.309 ± 0.125 versus 1.370 ± 0.127, p  = 0.04). The presence of fractures in T1D was associated with lower TBS (odds ratio = 0.024, 95 % confidence interval (CI) = 0.001–0.875; p  = 0.042) but not with age or BMI. TBS and HbA1c were independently associated with fractures. The area-under-the curve (AUC) of TBS was similar to that of total hip BMD in discriminating T1D patients with or without prevalent fractures. In this set-up, a TBS cutoff <1.42 discriminated the presence of fractures with a sensitivity of 91.7 % and a specificity of 43.2 %. Conclusions TBS values are lower in T1D patients with prevalent fractures, suggesting an alteration of bone strength in this subgroup of patients. Reliable TBS cutoffs for the prediction of fracture risk in T1D need to be determined in larger prospective studies.