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Seasonal maps of dual view retrieved mid-visible AOD and AODf for four selected years (1998, 2008, 2019, 2020) are introduced and assessed in comparisons to MODIS retrievals and general data of an aerosol climatology. Due to different sensor capabilities (ATSR-2, AATSR and SLSTR) there are still unresolved inconsistencies so that decadal regional trends are not as detectable as with MODIS retrievals. SLSTR retrieval, however, agree with MODIS retrievals that 2020 Covid impacts on AOD values (via comparisons to the pre-COVID 2019 reference) are at best minor and secondary to natural anomalies by wildfires and dust. In radiative transfer applications the dual view AOD data for the four years are processed in the MAC climatology environment to determine aerosol associated radiative effects for total aerosol and for anthropogenic aerosol. Even though the calculated radiative effects are affected by retrieval AOD retrieval tendencies, climate relevant TOA net-flux changes are consistent to result with AOD data from other satellite sensors and a general climatology: −0.9 W/m2 for total aerosol with a significant greenhouse effect and −0.8 and −0.2 W/m2 for anthropogenic aerosol with and without indirect effects, respectively. Aside from global averages, seasonal maps highlight the diversity of regional and seasonal radiative effects.

Purpose: To explore associations between the characteristics of people with epilepsy (PWE) and their attitudes toward generic substitution of antiseizure drugs (ASDs) in epilepsy. Methods: This was a cross-sectional survey study directed at adults with epilepsy using selected brand drugs: Keppra®, Lamictal®, Lyrica® or Topimax®. Symptoms of anxiety and depression, sense of self-efficacy, and beliefs about medicines were assessed. Caregivers were asked to answer for persons with intellectual or communicative difficulties. Results: The total response rate was 41% (n = 178). Almost half (46%) of subjects stated that they would oppose generic substitution (Gen-NEG) if suggested by their neurologist, while 71% would worry about adverse effects and/or increased seizure frequency after a putative switch. Age ≥50 increased the odds of being Gen-NEG (adjusted OR: 2.20, 95% CI: 1.18–4.11). Negative associations with both Gen-NEG and worriers were found for education level of high-school diploma or above, employment/studies, and prior experience of generic ASD switch. The proportion of worriers was much higher among caregivers (21/22) compared to subjects with epilepsy (106/156). Conclusion: High proportions of PWE express concerns regarding generic substitution of ASDs. The elderly and caregivers seem to express particular concerns. Identifying ways to diminish negative outcomes and worries in connection with a switch is an important future field of research in order to ensure high quality, cost-effective health care for the most vulnerable people in our societies. (Less)

We present an analysis of Rapid Keck Spectroscopy of the CVs AM Her (polar) and SS Cyg (dwarf nova). We decompose the spectra into constant and variable components and identify different types of variability in AM Her with different characteristic timescales. The variable flickering component of the accretion disc flux md the observational characteristics of a small flare in SS Cyg are isolated.

Background and aims The vasopressin analogue desmopressin has demonstrated efficacy in decreasing bleeding time by increasing the circulating levels of coagulation factor VIII and von Willebrand factor, but also by direct effects on platelets. Previous studies have demonstrated contrasting results regarding the effect of desmopressin on platelets in vitro. The aim of this study was to investigate the dose-response effects of in vitro desmopressin in whole blood. Our hypothesis was that desmopressin could increase platelet function in anticoagulated whole blood being stored up to 4 hours. Methods Desmopressin was administered with up to four different concentrations to venous whole blood, sampled with standard vacutainer tubes from 10 healthy volunteers after consent. Platelet function was analyzed with three different point-of-care techniques: Multiplate platelet aggregometry with adenosine diphosphate, collagen, thrombin receptor activating peptide-6, ristocetin and arachidonic acid agonists, tissue factor-activated thromboelastometry and Sonoclot glass bead viscoelastic coagulation tests at baseline and 4 hours later using different activator reagents. Results Thromboelastometry and Sonoclot did not show any significant change between baseline and 4 h later. A significant decrease in area under curve (AUC) could be seen with the Multiplate between baseline and after 4 h. Desmopressin did not improve any of these tests at baseline or during a 4 h storage and incubation period. Conclusion In vitro administered desmopressin could not increase normal platelet function or coagulation being measured with thromboelastometry and Sonoclot. Multiplate indicated decreased platelet aggregation over time, without any effect of in vitro added desmopressin.

Real-time quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) is increasingly used to monitor responses in chronic myeloid leukaemia (CML). The peripheral blood BCR-ABL/ABL ratio, as assessed by Q-RT-PCR, has been shown to correlate with the contemporary cytogenetic response in patients receiving imatinib (Glivec, Gleevec). We have used Q-RT-PCR to monitor the early molecular response to 4 weeks and 3 months of imatinib therapy, in 47 patients with established CML. After 4 weeks of imatinib therapy, patients whose BCR-ABL/ABL ratio had fallen to less than 50% that of baseline had a significantly higher probability of achieving a major cytogenetic response after 6 months of therapy, when compared with those whose ratio did not fall by this amount (P < 0.001). Similarly, patients whose ratio at 3 months was less than 10% of that at baseline had a significantly higher probability of achieving a major cytogenetic remission at 6 months (P < 0.001). Patients who achieved these falls in their BCR-ABL/ABL ratio at either 4 weeks or 3 months had a superior progression-free survival at a median follow-up of 16.5 months (P = 0.01 and 0.003 respectively). These effects were independent of patient age and disease stage. The occurrence of peripheral blood cytopenias sufficiently severe to interrupt therapy was unrelated to progression-free survival. In conclusion, the data suggest that the early trend in the BCR-ABL/ABL ratio may be clinically useful for the early identification of patients destined to fare poorly on imatinib.

Summary. Imatinib mesylate (trade name Glivec® or Gleevec) is emerging as an important therapy in the management of chronic myeloid leukaemia (CML). It is clinically useful to monitor the cytogenetic response to imatinib, although frequent marrow examinations are inconvenient. We have used serial real-time reverse transcription–polymerase chain reaction (RT-PCR) to monitor the ratio of peripheral blood BCR–ABL to normal ABL transcripts in 43 patients receiving imatinib, and compared the results to concurrent conventional bone marrow (BM) cytogenetics. After 6 months of treatment, 13 cases were complete cytogenetic responders, defined as all BM metaphases negative for the Philadelphia (Ph) chromosome. In these patients, the BCR–ABL/ABL ratio was less than 0·08%. Six cases achieved a partial cytogenetic response (1–35% Ph-positive BM metaphases) and their BCR–ABL/ABL ratio was between 0·08 and 10%. In total, 24 cases were cytogenetic non-responders, and their BCR–ABL/ABL ratio exceeded 11%. The data suggested that the 6-month BCR–ABL/ABL ratio may reliably predict the contemporary marrow cytogenetic response. It was concluded that serial real-time RT-PCR may offer a convenient surrogate assessment of the marrow cytogenetic response to imatinib therapy in CML.

In an independent study in which we used 10-12 month old male C57BL/6 mice to investigate deoxycorticosterone Acetate (DOCA) and salt (1% saline) induced hypertension, we unexpectedly found that a numbers of mice died of aortic aneurysm rupture. Since aortic aneurysm affects 4-8% elderly men and elevated plasma aldosterone (ALDO) concentrations in patients have been linked to a spectrum of cardiovascular diseases, we therefore tested the possibility that activation of the mineralocorticoid receptor (MR) by DOCA and salt may be involved in aortic aneurysm formation. We reported here that that administration of 10-month-old male C57BL/6 mice with DOCA and salt, but neither DOCA nor salt alone, potently induced abdominal aortic aneurysm (AAA, 62%), thoracic aortic aneurysm (TAA, 44%), and aortic rupture (18%). ALDO and salt also induced similar high rates of AAA (58%), TAA (50%), and aortic rupture (42%). Histological and immunohistological examinations of cross-sections of AAA and TAA at the elastin degradation site demonstrated that DOCA and salt or ALDO and salt induced aortic aneurysm resembled human aortic aneurysm with respect to elastin degradation, macrophage infiltration, smooth muscle cell degeneration and apoptosis, and oxidative stress. Moreover, DOCA and salt also induced aortic aneurysm in 10-week-old mice but with lower incidence and less severe than that in 10-month-old mice. Interestingly, aortic aneurysm formation did not correlate with the increase in blood pressure induced by DOCA and salt. Systemic administration of the angiotensin converting enzyme inhibitor, enalapril, or angiotensin type 1 receptor antagonist, losartan, did not affect DOCA and salt-induced aortic aneurysm. In contrast, the MR antagonist spironolactone significantly attenuated DOCA and salt induced aortic aneurysm. In summary, our study describes a novel aortic aneurysm animal model induced by MR agonist and high salt, and reveals a previously unrecognized but potentially significant role of aldosterone in the pathogenesis of aortic aneurysm. These findings imply that MR antagonists may be effective in the treatment of some aortic aneurysms.

Objective To design an instrument for scoring residents learning pediatric disaster triage (PDT), and to test the validity and reliability of the instrument. Methods We designed a checklist-based scoring instrument including PDT knowledge and skills and performance, as well as a global assessment. Learners' performance in a 10-patient school bus crash simulation was video recorded and scored with the instrument. Learners triaged the patients with a color-coded algorithm (JumpSTART, Simple Triage and Rapid Treatment). Three evaluators observed the recordings and scored triage performance for each learner. Internal and construct validity of the instrument were established via comparison of resident performance by postgraduate year (PGY) and correlating instrument items with overall score. Validity was assessed with analysis of variance and the D statistic. We calculated evaluators' intraclass correlation coefficient (ICC) for each patient, skill, triage decision, and global assessment. Results There were 37 learners and 111 observations. There was no difference in total scores by PGY ( P = .77), establishing internal validity. Regarding construct validity, most instrument items had a D statistic of >0.5. The overall ICC among scores was 0.83 (95% confidence interval [CI] 0.74–0.89). Individual patient score reliability was high and was greatest among patients with head injury (ICC 0.86; 95% CI 0.79–0.91). Reliability was low for an ambulatory patient (ICC 0.29; 95% CI 0.07–0.48). Triage skills evaluation showed excellent reliability, including airway management (ICC 0.91; 95% CI 0.86–0.94) and triage speed (ICC 0.81; 95% CI 0.72–0.88). The global assessment had moderate reliability for skills (ICC 0.63; 95% CI 0.47–0.75) and knowledge (ICC 0.64; 95% CI 0.49–0.76). Conclusions We report the validity and reliability testing of a PDT-scoring instrument. Validity was confirmed with no performance differential by PGY. Reliability of the scoring instrument for most patient-level triage, knowledge, and specific skills was high.

Apolipoprotein (apo) E is a protein involved in both lipid metabolism and neuroprotection. Recently, it has been suggested that apoE may play a role in the regulation of food intake and body weight in rodents. However, rodent plasma apoE is difficult to purify in reasonable amounts due to numerous time-consuming steps. To circumvent this, we created a bacterial expression system for the efficient production of large amounts of rat apoE. We inserted rat apoE DNA into the pET30 expression vector and overexpressed the proteins in Escherichia coli strain BL21 (DE3). A histidine tag present at the N-terminus allowed for easy purification of the recombinant protein. The tag was removed with an IgA protease (Igase) from Neisseria gonorrhoeae leaving the mature form of the protein. The use of Igase was important as several more common proteases routinely cleave apolipoproteins at undesired sites. The recombinant protein was then compared both structurally and functionally to rat plasma apoE. This expression system will be highly useful for probing the ability of rat apoE to mediate food intake in rats.

Real-time quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) is increasingly used to monitor responses in chronic myeloid leukaemia (CML). The peripheral blood BCR-ABL/ABL ratio, as assessed by Q-RT-PCR, has been shown to correlate with the contemporary cytogenetic response in patients receiving imatinib (Glivec, Gleevec). We have used Q-RT-PCR to monitor the early molecular response to 4 weeks and 3 months of imatinib therapy, in 47 patients with established CML. After 4 weeks of imatinib therapy, patients whose BCR-ABL/ABL ratio had fallen to less than 50% that of baseline had a significantly higher probability of achieving a major cytogenetic response after 6 months of therapy, when compared with those whose ratio did not fall by this amount (P0.001). Similarly, patients whose ratio at 3 months was less than 10% of that at baseline had a significantly higher probability of achieving a major cytogenetic remission at 6 months (P0.001). Patients who achieved these falls in their BCR-ABL/ABL ratio at either 4 weeks or 3 months had a superior progression-free survival at a median follow-up of 16.5 months (P = 0.01 and 0.003 respectively). These effects were independent of patient age and disease stage. The occurrence of peripheral blood cytopenias sufficiently severe to interrupt therapy was unrelated to progression-free survival. In conclusion, the data suggest that the early trend in the BCR-ABL/ABL ratio may be clinically useful for the early identification of patients destined to fare poorly on imatinib.

Imatinib mesylate (trade name Glivec or Gleevec) is emerging as an important therapy in the management of chronic myeloid leukaemia (CML). It is clinically useful to monitor the cytogenetic response to imatinib, although frequent marrow examinations are inconvenient. We have used serial real-time reverse transcription-polymerase chain reaction (RT-PCR) to monitor the ratio of peripheral blood BCR-ABL to normal ABL transcripts in 43 patients receiving imatinib, and compared the results to concurrent conventional bone marrow (BM) cytogenetics. After 6 months of treatment, 13 cases were complete cytogenetic responders, defined as all BM metaphases negative for the Philadelphia (Ph) chromosome. In these patients, the BCR-ABL/ABL ratio was less than 0.08%. Six cases achieved a partial cytogenetic response (1-35% Ph-positive BM metaphases) and their BCR-ABL/ABL ratio was between 0.08 and 10%. In total, 24 cases were cytogenetic non-responders, and their BCR-ABL/ABL ratio exceeded 11%. The data suggested that the 6-month BCR-ABL/ABL ratio may reliably predict the contemporary marrow cytogenetic response. It was concluded that serial real-time RT-PCR may offer a convenient surrogate assessment of the marrow cytogenetic response to imatinib therapy in CML.

Adverse prognostic factors in CLL include functional impairment of the p53 pathway [Blood2002;100:1404] and the chromosomal aberrations del 17p13, del 11q23 and +12 [reviewed in Leukemia2002;16:993]. Intriguingly, TP53 is deleted at 17p13, ATM (an important positive regulator of p53) is deleted at 11q23, and MDM2 (an key negative regulator of p53) is amplified in +12. This suggests that p53 dysfunction might account for the deleterious effects of these chromosomal aberrations, and consequently that the two tests might provide similar prognostic information. To define the relationship between p53 dysfunction and karyotype, CLL clones from 178 patients were subjected to p53 functional analysis and interphase FISH for del 17p13, del 11q23, +12 and del 13q14. In order to assign cases with multiple FISH defects to single karyotypic groups, we used an hierarchical model, in which del 17p13, del 11q23, +12 and del 13q14 had a descending order of importance [N Engl J Med2000;343:1910]. The overall frequency of each hierarchical karyotype (17p−, 11q−, +12, and 13q−) was 16.3%, 16.3%, 12.4% and 33.1% respectively. p53 dysfunction, defined as impaired up-regulation of p21 (a transcriptional target of p53) in response to ionizing radiation (IR), was detected in 40.4% of cases using a validated FACS method. 5.1% of cases had the type A defect (baseline p53 increased), 35.4% the type B defect (baseline p53 not increased), and the remainder were classified as having a normal p53 functional response. The distribution of karyotype and p53 functional status is shown in Table 1. Table 1 Karyotype Type A p53 defect Type B p53 defect No p53 dysfunction Total 17p− 7 13 9 29 11q− 1 16 12 29 12+ 1 3 18 22 13q− 0 17 42 59 Normal 0 14 25 39 Total 9 63 106 178 p53 dysfunction was positively associated with 17p− (P < 0.001) and 11q− (P = 0.029), negatively associated with +12 (P = 0.023) and 13q− (P = 0.007), and neither positively or negatively associated with normal karyotype. The frequency of p53 dysfunction in cases with 17p−, 11q−, +12, 13q−, or no FISH defects was 69.0%, 58.6%, 18.2%, 28.8% and 35.9% respectively. The frequency of 17p−, 11q−, +12, 13q−, or no FISH defects was 28.6%, 24.3%, 5.7%, 24.3% and 20.0% respectively in cases with p53 dysfunction, and 8.5%, 11.3%, 17.0%, 39.0% and 23.6% respectively in cases with no detectable p53 dysfunction. Among cases with p53 dysfunction, there was an association between the type A defect and 17p− (P < 0.001). Interestingly, among 17p− cases, the proportion of cells harbouring the 17p13 deletion negatively correlated with the amount of IR-induced p21 up-regulation (r = −0.608, P < 0.001) and positively correlated with baseline p53 levels (r = 0.398, P = 0.033). Indeed, p53 dysfunction was detected in all 15 cases with more than 50% 17p13-deleted cells but in fewer than half of the cases with less than 50% deletion. Together, these findings indicate that adverse karyotype and p53 dysfunction provide overlapping but non-identical information. The association between p53 dysfunction and 17p−/11q− supports the idea of a shared pathogenetic mechanism. On the other hand, the imperfect nature of this association justifies the continued evaluation of p53 functional analysis as a prognostic factor in CLL.