Extraneous Background-Correction Program for Matrix Bound Multiple Point X-Ray Microanalysis

A program is described that allows online determination of extraneous background in multiple point X-ray microanalytical matrices. The program is based upon the calculations of the extraneous background for the film (when present), the standard and the unknown by (100 sec.) point analysis. The program searches for a peak-free part of the spectrum in which the calculated value for the extraneous background is about equal to the value in this region of the spectrum (=be). Online the contents of this be-region is subtracted from an unmanipulated continuum region in the vicinity of the element present in the unknown and standard (Pt). During the subsequently performed matrix analysis two arrays are acquired (P-b) and (b-be). From these two arrays, the Rx,st and subsequently the Rx,sp are calculated per pixel, which are converted to (be corrected) concentration arrays. In addition Z2/A-differences between standard and the analyzed specimen are corrected off-line. For each pixel the program judges whether the calculated concentration deviates from the value introduced for the standard. Once differences are registered, adequate corrections are made

The ‘province’ of the Dutch Republic in the international Republic of Letters

Because the world of learning within the geography of the Dutch Republic was characterized by dynamic patterns of migration, and because only a small minority of scholars corresponded in Dutch, the question arises whether there was any such thing as a ‘Dutch’ province within the international learned community. To what extent were scholars who corresponded from within the geographical coordinates of the United Provinces transnational in their epistolary contacts? We propose to measure and compare the strength of foreign relations by analysing correspondence traffic. We use epistolary networks as approximations of social networks, although the former is but a small part of the latter. Our analysis shows that the most active letter-writers had a nearly even ratio of foreign and Dutch correspondents and that foreign cities featured prominently in the intellectual geography of the Dutch Republic

Is the time in therapeutic range on coumarins predicted by previous time in therapeutic range?

Background The benefit of vitamin K antagonists depends on the time within the therapeutic range (TTR). A patient's previous TTR could be a factor in the decision to change the anticoagulation regimen. However, the predictive value of a previous TTR for a future TTR is not well established, nor is it clear which TTR should prompt action. Objectives To investigate the predictive performance of a TTR and identify a threshold below which no recovery of TTR should be expected. Patients/Methods From 18 031 patients who used acenocoumarol in a first-line anticoagulation clinic, a TTR was calculated over multiple periods of 90, 180, and 365 days each. We assessed the correlation between baseline and later TTR and the separation between groups by quintile of baseline TTR. We describe the proportion of patients who obtain a TTR >= 70% conditional on baseline TTR. Results The correlation between baseline and later TTR was 0.25 (95% confidence interval [CI], 0.24-0.26), 0.27 (95% CI, 0.26-0.28) and 0.34 (95% CI, 0.32-0.35) for analyses over 90, 180, and 365 days. Corresponding c statistics for discrimination by baseline group were 0.60, 0.61, and 0.63. The probability to obtain a TTR >= 70% increased with baseline TTR: from 42% with a baseline TTR of 50%-65% when TTR was 100% (TTR calculated over 180 days). Conclusions We conclude that a current TTR hardly predicts a future TTR. Physicians and patients should deliberate together which probabilities to accept, take measures to improve TTR, and consider potential alternatives

Quality of life after switching from well-controlled vitamin K antagonist to direct oral anticoagulant:Little to GAInN

BACKGROUND: Direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) prevent thromboembolism in atrial fibrillation (AF). DOAC have a fixed dosing regimen and obviate INR monitoring. Therefore, DOAC presumably affect quality of life (QoL) less than VKA. However, some VKA users appreciate the monitoring. A high time in the therapeutic range (TTR) leads to a lower impact on QoL. We assessed the influence of switching from well-controlled VKA to a DOAC on QoL. METHODS: In the GAInN study, 241 patients with AF, a TTR ≥ 70%, and neither bleeding nor thrombosis while on VKA were randomised to switching to DOAC (n = 121) or continuing VKA (n = 120). Health-related (SF-36) and anticoagulation-related QoL (PACT-Q) was assessed at baseline and after six and twelve months of follow-up. RESULTS AND CONCLUSION: SF-36 development did not differ between groups. After one year, average PACT-Q Convenience improvement was 2.5 (0.3-4.7) higher on DOAC. DOAC users were 6percentage points (95%CI -4-16) more likely to improve >5 points on Convenience; 22 pp. (95%CI 1-43) in patients who scored <95/100 at baseline. The probability to meaningfully improve on PACT-Q Satisfaction was 12 pp. (95%CI 0-25) higher on DOAC. However, 5 (4.1%) and 4 (3.3%) DOAC users resumed VKA because of side-effects and patient preference. Switching from well-controlled VKA to DOAC for AF leads to a higher probability of improved PACT-Q convenience and satisfaction, but also to a higher risk of side-effects. Arguably only patients who are not satisfied with VKA should switch, because they have more to gain by switching

Effect of switching from acenocoumarol to phenprocoumon on time in therapeutic range and INR variability:A cohort study

BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase

Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly administered cefepime in rabbits

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 × 108 colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1–. There was a significant reduction in the elimination half-life by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasma-concentration-time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits

Etiology of Experimental Calcium Oxalate Monohydrate Nephrolithiasis in Rats

In a rat-model system, tubular crystal retention as a possible mechanism for the etiology of nephrolithiasis in man, was studied by conventional transmission electron microscopy. The animals were supplied for nine days with a crystal-inducing diet, with ethylene glycol plus NH4Cl in their drinking-water. After this induction period, a two day regime with fresh drinking-water was included, to allow crystals to be removed by spontaneous crystalluria. After aldehyde fixation of the rat kidneys, large crystals were seen inside the tubular lumen. The crystals were attached to cell surfaces and covered by neighboring epithelial cells. Some crystals were overgrown by several epithelial cells and underwent a process of so-called exotubulosis, resulting in free or cell-surrounded crystals in the interstitium, and possibly in crystals in Giant cells. To investigate the fate of the retained crystals, some animals were additionally exposed to a low-oxalate challenge from drinking water containing 0.1 volume per cent of ethylene glycol for 12 or 30 days, respectively. It was assumed that this would interfere with the retained intratubular or interstitial crystals, and allow the crystals to grow into mini-stones. This was not observed. After the oxalate challenge, no crystals were found to be retained in the tubules (free or covered by cells). Interstitial crystals were observed, but it remains to be demonstrated whether such crystals actually grow into mini-stones or that they are removed by the sterile inflammation process observed