Arterial punctures (APs) for arterial blood gas (ABG) analyses are much-used medical procedures. To date, no large studies have been conducted on the major complication rate of APs. We aimed to ...describe the risk of major complications within 7 days after puncture and investigate whether using antithrombotic medication affected this.
We included all APs performed for ABG analysis at three Danish hospitals from January 1, 1993 to February 25, 2013. We excluded APs ordered by the anaesthesiology department, intensive care unit (ICU) or in patients <18 years old. Data on the patient level were extracted from the Danish National Patient Registry, Danish Civil Registration System and Odense Pharmaco-Epidemiologic Database (OPED), the latter providing us with information on antithrombotic medication. Initially, two clinicians compiled a list with all procedures and diagnoses that could possibly be a consequence of APs. The selected procedures and diagnoses were further categorised independently by three surgeons and used to indicate the complication rate.
We analysed 473 327 APs and found 669 (0.14%, 95% CI 0.13-0.15) APs led to major complications: embolisms or thrombosis (49.0%), aneurysms (15.4%), nerve damage (1.5%), arteriovenous fistulas (0.6%) or of another kind (33.5%). The identified major complication rates in patients on antithrombotic medication were increased (OR 1.31, 95% CI 1.07-1.61).
APs for ABG analyses are safe procedures. The major complication rate within 7 days was 0.14% (95% CI 0.13-0.15). Patients on antithrombotic medication carry an increased risk of developing major complications.
Development of diamond-based diagnostics for next-generation XFELs Padilla, R.; Gonzalez, E.; Kachiguine, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2023, Letnik:
1057
Journal Article
Recenzirano
Odprti dostop
The composition and performance of three different diamond sensor based pass-through diagnostics are presented. A position-sensitive quadrant sensor was designed and characterized using the XPP beam ...at the SLAC LCLS, demonstrating a generated-charge resolution of 0.025 pC and a position sensitivity of 2 μm, measurable pulse-by-pulse at a repetition rate of up to 50 MHz. A compact signal path capable of repetition rates up to 1 GHz was used to characterize the charge collection properties of diamond sensors as a function of the density of electron-hole pairs created within the sensor, finding a limit of approximately 1016 electron-hole pairs per cm3 beyond which the collection efficiency and time began to degrade. Finally, a proposed scheme for measuring ionizing radiation at multi-GHz rates is presented, along with results preliminarily demonstrating signal transport capability in excess of 5 GHz.
Contemporary research on congressional activism in American foreign policy indicates that individual members of Congress have become more assertive over time. If so, the motivations and interests of ...individual members of Congress are even more important for understanding American foreign policy. What factors motivate members of Congress as they take a more active role in foreign policy than ever before? Recent research suggests that partisanship has increased in importance over the past three decades. This paper examines Senate ratification votes on the Limited Test Ban Treaty (1963), Nuclear Non-proliferation Treaty (1968), Chemical Weapons Convention (1997) and Comprehensive Test Ban Treaty (1999) to gauge the relative importance of three determinants of congressional voting - partisanship, ideology, and electoral concerns - while also controlling for region, career background, and other variables. Examining treaties in both the Cold War and Post-Cold War eras, we find that our model becomes increasingly powerful in the post-Cold War treaties and, especially, that partisanship increases substantially from the Cold War treaty votes to the post-Cold War votes.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Parents have a significant role in the prevention of smoking among their children, yet there is scarce research into what parents actually do to encourage non-smoking. This paper examines the actions ...that a sample of mothers of grades 7 and 8 students in southern Sydney have taken with regard to smoking prevention and the factors associated with taking action. Data were collected from 1113 mothers through a self-completed questionnaire sent home and returned by students. About four out of five mothers had had an open discussion about the importance of not smoking and 28% had enforced non-smoking rules. Non-smoking mothers, mothers with a more positive attitude towards their role in preventing their child from smoking and mothers who were worried about their child smoking were more likely to have enforced rules. After adjusting for maternal smoking, level of worry about their child smoking and attitude towards smoking, mothers speaking a language other than English at home were significantly less likely to have discussed not smoking, but tended to have enforced non-smoking rules. When an associated study of the children of these mothers is considered, where students speaking a language other than English at home smoked less than those speaking English, it suggests that enforcing non-smoking rules is an effective strategy for at least delaying smoking among grades 7 and 8 students.
Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” phenotype usually respond well to BRAF inhibitor ...therapy, but these melanomas also contain subpopulations of the de novo resistance “AXL‐high” phenotype. > 50% of melanomas progress with enriched “AXL‐high” populations, and because AXL is linked to de‐differentiation and invasiveness avoiding an “AXL‐high relapse” is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF‐induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re‐activation in a paracrine manner. Most importantly, EDN1 not only supports MITF‐high populations through the endothelin receptor B (EDNRB), but also AXL‐high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL‐high‐expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL‐high cells.
Synopsis
Melanoma heterogeneity challenges durable responses to BRAF targeting. During BRAF‐inhibitor treatment endothelin‐1 (EDN1) supports phenotype heterogeneity thereby allowing outgrowth of resistant cells. Blocking EDN1 signalling can overcome this support.
Phenotype heterogeneity in melanoma is characterised by MITF‐high and AXL‐high subpopulations.
Tumours enriched in AXL‐high subpopulations are resistant to BRAF‐inhibitor treatment.
BRAF inhibitor‐responding tumours contain a small population of AXL‐high cells.
Treatment with BRAF inhibitor induces upregulation of EDN1, and paracrine acting EDN1 supports the outgrowth of AXL‐high subpopulations.
Treatment with EDN receptor (EDNR) antagonists overcomes paracrine EDN1 signalling and prolongs BRAF‐inhibitor responses.
Melanoma heterogeneity challenges durable responses to BRAF targeting. During BRAF‐inhibitor treatment endothelin‐1 (EDN1) supports phenotype heterogeneity thereby allowing outgrowth of resistant cells. Blocking EDN1 signalling can overcome this support.
Mutations in breast cancer susceptibility gene BRCA1 (breast cancer early-onset 1) are associated with increased risk of developing breast and ovarian cancers. BRCA1 is a large protein of 1863 ...residues with two small structured domains at its termini: a RING domain at the N-terminus and a BRCT (BRCA1 C-terminus domain) repeat domain at the C-terminus. Previously, we quantified the effects of missense mutations on the thermodynamic stability of the BRCT domains, and we showed that many are so destabilizing that the folded functional state is drastically depopulated at physiological temperature. In the present study, we ask whether and how reduced thermodynamic stability of the isolated BRCT mutants translates into loss of function of the full-length protein in the cell. We assessed the effects of missense mutants on different stages of BRCA1-mediated DNA repair by homologous recombination using chicken lymphoblastoid DT40 cells as a model system. We found that all of the mutations, regardless of how profound their destabilizing effects, retained some DNA repair activity and thereby partially rescued the chicken BRCA1 knockout. By contrast, the mutation R1699L, which disrupts the binding of phosphorylated proteins (but which is not destabilizing), was completely inactive. It is likely that both protein context (location of the BRCT domains at the C-terminus of the large BRCA1 protein) and cellular environment (binding partners, molecular chaperones) buffer these destabilizing effects such that at least some mutant protein is able to adopt the folded functional state.
COVID-19 may not be a ‘youth disease’ but it nevertheless impacts the life of young people dramatically, loneliness and a negative mood being an unexpected additional pandemic. Many young people rely ...on social media for their feeling of connectedness with others. However, social media is suggested to have many negative effects on people’s anxiety. Instead of self-disclosing to others, design may develop alternatives to employ social robots for self-disclosure. In a follow-up on earlier work, we report on a lab experiment of self-disclosing negative emotions to a social media group as compared to writing a conventional diary journal or to talking to an AI-driven social robot after negative mood induction (i.e., viewing shocking earthquake footage). Participants benefitted the most from talking to a robot rather than from writing a journal page or sharing their feelings on social media. Self-disclosure on social media or writing a journal page did not differ significantly. In the design of interventions for mental well-being, human helpers thus far took center stage. Based on our results, we propose design alternatives for an empathic smart home, featuring social robots and chatbots for alleviating stress and anxiety: a social-media interference chatbot, smart watch plus speaker, and a mirror for self-reflection.
Mice lacking 25-hydroxycholecalciferol 25(OH)D-1α-hydroxylase (CYP27B1) are growth retarded, hypocalcemic, and have poor bone mineralization. We tested whether high dietary cholecalciferol (VD3) ...could exert effects in the absence of CYP27B1 in vivo. Weanling male wild-type (WT) and CYP27B1 knockout (KO) mice were fed either a 2% calcium (Ca), 20% lactose rescue diet or an AIN93G diet (0.5% Ca, 0.4% phosphorus) containing 1000 (1K, the rodent requirement, 25 μg), 10,000 (10K, 250 μg), or 20,000 (20K, 500 μg) IU VD3/kg diet until 12 wk when blood and tissues were taken. Serum 25(OH)D was >90 nmol/L in the 1K diet group and increased >4-fold in mice fed 10K and 20K diets. The 1K diet impaired growth and caused hypocalcemia in KO mice; the 10K and 20K diets were as effective as the high Ca rescue diet in preventing these outcomes. High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D₉K) and kidney (CYP27B1, 24-hydroxylase, calbindin D₉K) of KO mice. Micro-computed tomography of femora revealed complete recovery of cortical bone in KO mice fed either the rescue or 10K diets but only partial recovery of trabecular bone measures (e.g. 40% lower bone volume, 20% lower trabecular thickness, and 23% increase in trabecular separation). These data show that very high serum 25(OH)D can influence Ca and bone metabolism independent of its conversion to 1,25 dihydroxycholecalciferol. However, neither high dietary Ca nor high dietary VD3 is sufficient to fully recover the phenotype of CYP27B1 KO mice.
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