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Funding Acknowledgements Type of funding sources: None. Introduction Wearable technology is increasingly used to identify episodes of atrial fibrillation (AF). However, most validation studies using single-lead electrocardiograms (ECGs) only included patients with either sinus rhythm or AF and, therefore, likely overestimate the sensivities and specificities of AF detection algorithms. Purpose We sought to evaluate the diagnostic accuracy of the Apple Watch and CART-I ring AF algorithms in a broad cohort of patients with pre-existing cardiovascular disease. Methods In this single-centre prospective study, individuals with known cardiovascular disease underwent simultaneous 12-lead ECG recordings with a 30-second single-lead ECG from an Apple Watch Series 6 and a CART-I Ring. The order of devices was randomly assigned. Two cardiologists independently evaluated the 12-lead ECGs for the presence of AF; any disagreements were resolved by a third cardiologist. The wearable devices’ algorithm labelled ECGs as "AF", "Not AF" or "Unclassified". Diagnostic accuracy was determined by calculating the sensitivity and specificity for each device and comparing them using McNemar’s test. The primary analysis included Unclassified ECGs, which categorised as false-positive (no AF on the 12-lead ECG) or false-negative (AF on the 12-lead ECG). A separate analysis excluded all Unclassified ECGs. Results We enrolled 400 consecutive patients. Seven patients had suboptimal 12-lead ECGs and were excluded from the analysis. The median age was 63 (58-75) years, and 73% of the population was male. Baseline demographics are depicted in Table 1. A total of 1573 ECGs were analysed. Forty-two percent of patients were in AF, 9.9% were in an atrial tachycardia, 3.3% had sinus rhythm with frequent ectopy. If all ECGs were included, the CART-I ring's AF sensitivity was significantly higher than the Apple Watch, at 86.6% (95% CI: 80.6%-91.1%) and 67.4% (95%CI: 60.0%-74.1%), respectively (Fig 1). Similarly, AF specificity was higher with CART-I ring (89.4% [95%CI: 84.7%-92.8%]) when compared to the Apple Watch (74.9% [95%CI 68.9%-80.1%]). The Apple Watch had more Unclassified ECGs than CART-I ring (78 vs. 2, respectively). They were divided into three categories: 14.1% as HR 50 bpm, 10.21% as HR > 120 bpm, and 76.9% as Inconclusive (Table 2). When Uclassified ECGs from the Apple Watch were excluded, AF sensitivity and specificity improved by 16.33% (p=0.002) and 13.38% (p Conclusion In patients with cardiovascular disease, the diagnostic accuracy of AF detection from a single-lead ECG was lower than previously reported. The CART-I ring's AF sensitivity and specificity outperformed those of the Apple Watch. One in three patients with AF went undetected by the Apple Watch.

Funding Acknowledgements Type of funding sources: None. Introduction The 2020 ESC AF management guideline states that a 30-second single-lead electrocardiogram (sl-ECG) can be used to diagnose atrial fibrillation, but advises caution as most validation studies used small, carefully selected cohorts and are prone to bias. Patients with frequent ectopy, other atrial arrhythmias, and cardiac implantable electronic devices, which are important sources of false-positive detection, are noticeably absent from many studies. Purpose We sought to compare the diagnostic accuracy of the Apple Watch and CART-I ring automated AF detection to physician interpretation of a sl-ECG in a broad cohort of patients with pre-existing cardiovascular disease. Methods This prospective single-centre randomised study recruited patients with known cardiovascular disease in a large UK tertiary centre. All patients underwent simultaneous 12-lead ECG recordings with a 30-second sl-ECG from an Apple Watch Series 6 and a CART-I Ring. The order of devices was randomly assigned. Two cardiologists independently adjudicated all ECGs; any disagreements were resolved by a third cardiologist. The wearable devices’ algorithm labelled ECGs as "AF", "Not AF" or "Unclassified". Unclassified ECGs were categorised as false-positive (no AF on the 12-lead ECG) or false-negative (AF on the 12-lead ECG). Diagnostic accuracy was determined by calculating AF sensitivity and specificity for each device and comparing it to 12-lead ECGs. Results A total of 1600 ECGs from 400 consecutive patients were recorded. Seven patients were excluded due to uninterpretable 12-lead ECGs. The median age was 63 (58-75) years; 24% were female; 75.1% had coronary artery disease; 64% had a history of AF; and 10 % had undergone previous cardiac surgery. Interobserver reproducibility for sl-ECGs was high, with levels of agreement for the Apple Watch and the CART-I ring being 89.8% and 91.1%, respectively (p=0.54). The CART-I ring’s AF sensitivity from automated detection was significantly higher than the Apple Watch’s (mean difference 18.6%; 95%CI 17.0%-20.6%, p=0.03). Physician interpretation of the Apple Watch sl-ECGs led to a significant increase in AF sensitivity and specificity, 95.8% (95% CI: 91.6 %-97.9%) and 90.8 % (95% CI: 86.2 %-93.9%), respectively (Figure 1B). In contrast, physician interpretation of the CART-I ring’s sl-ECG resulted in higher AF sensitivity (94.6% [95% CI: 90.0%-97.1%]) but a marginal decrease in specificity (89.4% [95% CI: 84.8%-92.8%]). There was no statistically significant difference in AF detection between physician-interpreted sl-ECG from the wearable devices: 4.74% difference in AF sensitivity (p=0.12) and 1.32% difference in AF specificity (p=0.75). Conclusion In patients with cardiovascular disease, automatic AF detection algorithms from wearable devices have a higher rate of false-positive detections than previously reported. Physician-interpreted sl-ECGs have excellent diagnostic accuracy for AF.

The Alpine fault is a high slip-rate plate boundary fault that poses a significant seismic hazard to southern and central New Zealand. To date, the strongest paleoseismic evidence for the onshore southern and central sections indicates that the fault typically ruptures during very large (Mw≥7.7) to great “full-section” earthquakes. Three paleoseismic trenches excavated at the northeastern end of its central section at the Toaroha River (Staples site) provide new insights into its surface-rupture behavior. Paleoseismic ruptures in each trench have been dated using the best-ranked radiocarbon dating fractions, and stratigraphically and temporally correlated between each trench. The preferred timings of the four most recent earthquakes are 1813–1848, 1673–1792, 1250–1580, and ≥1084–1276 C.E. (95% confidence intervals using OxCal 4.4). These surface-rupture dates correlate well with reinterpreted timings of paleoearthquakes from previous trenches excavated nearby and with the timing of shaking-triggered turbidites in lakes along the central section of the Alpine fault. Results from these trenches indicate the most recent rupture event (MRE) in this area postdates the great 1717 C.E. Alpine fault rupture (the most recent full-section rupture of the southern and central sections). This MRE probably occurred within the early nineteenth century and is reconciled as either: (a) a “partial-section” rupture of the central section; (b) a northern section rupture that continued to the southwest; or (c) triggered slip from a Hope-Kelly fault rupture at the southwestern end of the Marlborough fault system (MFS). Although, no single scenario is currently favored, our results indicate that the behavior of the Alpine fault is more complex in the north, as the plate boundary transitions into the MFS. An important outcome is that sites or towns near fault intersections and section ends may experience strong ground motions more frequently due to locally shorter rupture recurrence intervals.

Background The CAMI-1 study dealt with the depletion of CRP by apheresis in patients with acute myocardial infarction (AMI). CRP, the prototype human acute phase protein, has been known as a marker of poor prognosis in AMI and independently predicts 30-day mortality. Methods 66 STEMI patients were enrolled following complete coronary revascularization (2–12 h after AMI). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. A specific CRP adsorber removed ≤79% of the original CRP. 6000 ml of plasma was treated via peripheral venous access. Primary endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 3–9 days after STEMI. Results Aphereses sessions were well tolerated with no relevant side effects. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24h after the onset of symptoms (CRP gradient). The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP gradients. The mean CRP gradient does not differ between both groups, whereas the mean area under the curve (AUC) of CRP within the first 72 h after AMI does. Thus, there was no bias in CRP kinetics between the two groups. The AUC of CRP is a significant indicator for infarct size (p=0.002), LVEF (p Conclusions For the first time we find an unequivocal association between myocardial infarct size and the AUC of CRP. The results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry). Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Pentracor GmbH

The Taupo Volcanic Zone (TVZ) in North Island, New Zealand, is the on-land continuation of the Tonga-Kermadec arc formed in the Quaternary at the obliquely convergent boundary of the Pacific and Australian tectonic plates. The central TVZ is a region of intense silicic volcanism and active rifting with a very high heat flux. Within this zone is a dynamic landscape affected by a dense, active fault network, the Taupo Rift. In this rift, the Ngakuru graben hosts fossil hydrothermal systems in an area parallel to numerous active faults including the east strand of Whirinaki Fault that forms a major structure. Using various geoscientific techniques including mapping, stratigraphy, paleoseismic trenching, and tephrostratigraphy, in conjunction with LiDAR-derived DEMs, we reconstruct and date the fault's rupture history along with hydrothermal activity (including silica-sinter development) since c. 40,000 calendar years ago (40 cal. ka) at a site near Hossack Road called “Meade”. Ages for Kawakawa (c. 25.4 cal. ka), Okareka (c. 21.8 cal. ka), Rotorua (c.15.6 cal. ka), Rotoma (c. 9.4 cal. ka), and Taupo (c. 1.7 cal. ka) tephras enabled us to date five identified fault rupture events using the Meade trench excavation. Slip rates of 2.66 ± 0.77 mm/yr (pre-Kawakawa tephra), 0.28 ± 0.04 mm/yr (between c. 25.4 ka and Taupo) and 0.51 ± 0.19 mm/yr (post-Taupo), and the recurrence interval of ∼5500 cal. yr during the last c. 25.4 cal. kyr, all correlate with events of similar ages determined from studies on other trenches on Whirinaki Fault. Intercalated with Tahuna tephra (c. 39.3 cal. ka) and additionally dated at c. 38.9 cal. ka using radiocarbon, the hydrothermal sinter began developing at the Meade site at c. 39 cal. ka and ceased by c. 21.8 cal. ka (marked by Okareka tephra). We examine the causative relationship between fault activity and the development of sinter by comparing the chronology of volcanic eruptions and fault rupturing events with that of sinter formation as recorded in three neighbouring sites, Mangatete, Matthews, and Fitzpatrick. The findings improve understanding of the complex rupture behaviour of faulting and provide evidence for relationships between tectonic and hydrothermal activities, which were additionally influenced by the impacts of climatic change and geomorphic processes on landscape evolution, within the late Quaternary period. The study also exemplifies the unique value of tephrochronology in helping to disentangle complex geological deposits and events in an extremely dynamic part of the Earth's surface (the Taupo Rift).

Background The CAMI-1 study dealt with the depletion of CRP by apheresis in patients with acute myocardial infarction (AMI). CRP, the prototype human acute phase protein, has been known as a marker of poor prognosis in AMI and independently predicts 30-day mortality. Methods 66 STEMI patients were enrolled in the study following complete coronary revascularization (2–12 h after the onset of symptoms). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. A specific CRP adsorber removed up to 79% of the original CRP. In each apheresis session, 6000 ml of plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 2–9 days after STEMI. Results Aphereses sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 9 to 279 mg/l. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the CRP concentration is significantly associated with the damage (infarct size, LVEF, circumferential strain) in the controls. This association was lost in the aphereses patients: they performed significantly better at all endpoints (infarct size, LVEF, circumferential strain) than the controls. The CRP apheresis significantly reduced myocardial damage. To our surprise, two apheresis patients had an infarct size of 0%. Conclusions For the first time we find an unequivocal association between myocardial infarct size and the CRP concentration. This is in some respects a surprise, since the basic assumption in AMI is that the vascular occlusion leads to primary damage and the reperfusion to secondary damage, which would not have led one to expect such a clear dose-response relationship as that observed here. In addition, our results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry). Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Pentracor GmbH

Investigations of modern coseismic ground surface deformation where fault rupture is absent typically rely on remote sensing techniques. We used monitoring of salt marsh vegetation and substrate for 3 years after the 22 February 2011 Christchurch earthquake (MW 6.2) to document the biological response to vertical deformation, to provide estimates of the amount of uplift and subsidence and ground-truth remote sensing data. Comparison of vegetation-derived vertical deformation with estimates from remote-sensing techniques (Light Detection and Ranging, Global Positioning System and Differential Interferometric Synthetic Aperture Radar) shows good agreement at sites where several decimetres of vertical movement occurred, and less agreement where smaller amounts of vertical movement occurred and/or where vegetation-monitoring sites were affected by differential movement of artificial structures such as roads and breakwaters. Biological and sedimentological changes observed in salt marshes around the Av...

The dextral–reverse Alpine Fault offsets alluvial terraces of the Maruia River at Calf Paddock. RTK‐GPS surveying of the faulted terraces yields detailed measurements of fault slip across terraces T1–T5. Pits were excavated to log the stratigraphy, date the deposits and to thereby constrain fault slip rates for this site. The mean of the four largest dextral offsets across terrace T2 is 12.0 ± 1.3 m. The corresponding mean vertical offset is 1.6 ± 0.6 m. A single charcoal date with an age of 1095–1275 cal yr BP is used to derive minimum dextral and reverse slip rates of 10 ± 2 and 1.3 ± 0.5 mm/yr, respectively. These rates are comparable with others observed nearby at Little and Lost Mary creeks and from previous studies at Calf Paddock. These new late Holocene slip rate estimates highlight the northeastward decrease in strike-slip and dip-slip rate along the northern section of the Alpine Fault as motion is partitioned onto faults of the Marlborough Fault System. The lack of aseismic creep observ...

Background Inflammation is increasingly recognized as an important pathogenic feature in cardiovascular disease. In patients with STEMI, C-reactive protein (CRP), the prototype human acute phase protein, is a marker of poor prognosis and independently predicts 30-day mortality. In STEMI, CRP may indeed be intimately involved in myocardial damage by activating the complement system in the ischemic tissue. In animal experiments, CRP removal after STEMI reduces infarct size and results in a significantly better left ventricular ejection fraction (LVEF). Recently, in the multi-center matched-control pilot study on CRP apheresis in Acute Myocardial Infarction (CAMI1), a newly designed CRP adsorber has been demonstrated to efficiently and selectively lower CRP plasma levels in humans. Here, we present preliminary data of the ongoing trial. Methods Up to the present day, 67 STEMI patients were enrolled in the study following complete coronary revascularization. 32 patients received CRP apheresis, whereas 35 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (MRI) 5±3 days after STEMI. Results Apheresis sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 12 mg/l to 279 mg/l. The peak CRP level after AMI can be calculated precisely with at 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.95. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the apheresis patients no longer correlate with the control with regard to the endpoints infarct size, LVEF, longitudinal strain and circumferential strain. They perform significantly better at all endpoints. The CRP apheresis reduced the development of myocardial damage. Conclusions Here, an unequivocal association between infarct size and CRP is demonstrated for the first time. CRP apheresis following STEMI is feasible and safe. Our preliminary results in a small cohort show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis may emerge as a new therapeutic approach in the treatment of acute myocardial infarction.

Information on structure, stress, and their interrelationship is essential for understanding structurally controlled geothermal permeability. Active fault mapping, borehole image analysis, and well testing in the Te Mihi geothermal area, New Zealand, allows us to refine structural and fluid flow architecture of this resource. The Te Mihi area is structurally complex, comprising a set of NW dipping master faults containing pervasive SE dipping antithetic and splay structures in their hanging walls. These faults are also intersected by E-W striking faults. A localized, N-S striking structural trend is also observed at Te Mihi. In consideration with Global Navigation Satellite System velocity vectors, both active NE-SW and E-W striking faults create biaxial extension at Te Mihi, though the observed NE-SW SHmax direction suggests that contemporary extension is NW-SE dominated. Stress field perturbations coincide with structural complexities like fault splays and intersections and/or proximity to recently active E-W and NE-SW striking structures. Borehole fluid flow at Te Mihi is concentrated at NW dipping master fault intersections, travel time fractures on acoustic image logs, halo fractures on resistivity image logs, NE-SW and E-W striking fractures, intervals of high fracture density, and spatial concentrations of wide aperture fractures and recently active NE-SW and E-W striking fractures. This study suggests Te Mihi geothermal expression results from biaxial extension evident from active structural trend intersections and the predominance of NE-SW and E-W striking structures within permeable well zones. Biaxial extension is therefore an important control on crustal fluid flow within the Taupo Volcanic Zone and thus geothermal resource delineation.

Background Age-related chronic diseases are prevalent in HIV-infected persons in the antiretroviral therapy (ART) era. Bone mineral density (BMD) loss and emphysema have separately been shown to occur at a younger age and with lesser risk exposure in HIV-infected compared to HIV-uninfected individuals. In non-HIV infected smokers, emphysema has been shown to independently predict low BMD. We hypothesized that emphysema would independently associate with thoracic vertebral bone attenuation, a surrogate for bone mineral density, in HIV-infected individuals. Methods Clinical, pulmonary function, and radiographic data were analyzed for 164 individuals from the University of Pittsburgh’s HIV Lung Research Center cohort. Chest CT scans were used to quantify emphysema and compute Hounsfield Unit (HU) attenuation of the 4th, 7th, and 10th thoracic vertebrae. The association between mean HU attenuation values across the three vertebrae and radiographic emphysema, age, sex, body mass index (BMI), steroid use, viral load, CD4 count, and forced expiratory volume in the first second (FEV1) was assessed by univariate and multivariate analyses. Results In univariate analysis, mean HU attenuation decreased with increasing age (p

Objective Chronic obstructive pulmonary disease is a common comorbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other comorbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. Design Longitudinal observational study. Methods Total 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, and TNFα), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. Results In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse forced expiratory volume in one second (FEV1) percentage-predicted, and higher sCD163 associated with worse FEV1/forced vital capacity. IL-6, TNFα, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. Conclusion Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of chronic obstructive pulmonary disease in HIV-infected persons.

Wir berichten von einem 53-jahrigen Patienten mit ausgepragter Ruhedyspnoe und massiver Volumenuberladung bei dekompensiertem Cor pulmonale. Begleitend lag eine Niereninsuffizienz in Stadium 3 vor. Der Patient musste bei diuretikaresistenter Uberwasserung und CO2-Narkose intubiert und beatmet werden. Die massive Volumenuberladung konnten wir erfolgreich mithilfe der langsamen kontinuierlichen Ultrafiltration [“slow continuous ultrafiltration“ (SCUF)] behandeln. Das entzogene Volumen lag in 3 Tagen insgesamt bei 27,5 l. Die SCUF ist ein effektives und schonendes Verfahren, mit dem auch eine exzessive Volumenuberladung bei Diuretikaresistenz therapiert werden kann.

From a data set of 50 published and new fault exposures, we establish a 26,000 year record of associations between the timing of fault rupture in two sectors of the Taupo rift, New Zealand, and deposition on the fault scarps of rhyolitic fall tephra from the adjacent Okataina volcanic center. We also investigate processes that could be responsible for the time associations. From 40 high-resolution couplets of fault rupture and volcanic eruption (located up to 30 km distant), we show that 30% of the fault ruptures occurred when the volcano was erupting, whereas in 70% of the cases volcanism and faulting were independent. Other geological and geophysical information indicates that faulting in the Taupo rift is essentially tectonic and, thus, most of the cases with time association between fault rupture and volcanic eruption found in the fault exposures in this study are interpreted to be a manifestation of stress transfer between faults and magmatic storage zones beneath the volcanic center. In a few cases close (

The Mw 7.1 Darfield (Canterbury) earthquake of 4 September 2010 (NZST) was the first earthquake in New Zealand to produce ground-surface fault rupture since the 1987 Edgecumbe earthquake. Surface rupture of the previously unrecognised Greendale Fault during the Darfield earthquake extends for at least 29.5 km and comprises an en echelon series of east-west striking, left-stepping traces. Displacement is predominantly dextral strike-slip, averaging ~2.5 m, with maxima of ~5 m along the central part of the rupture. Maximum vertical displacement is ~1.5 m, but generally < 0.75 m. The south side of the fault has been uplifted relative to the north for ~80% of the rupture length, except at the eastern end where the north side is up. The zone of surface rupture deformation ranges in width from ~30 to 300 m, and comprises discrete shears, localised bulges and, primarily, horizontal dextral flexure. At least a dozen buildings were affected by surface rupture, but none collapsed, largely because most of the buildings were relatively flexible and robust timber-framed structures and because deformation was distributed over tens to hundreds of metres width. Many linear features, such as roads, fences, power lines, and irrigation ditches were offset or deformed by fault rupture, providing markers for accurate determinations of displacement.

The laboratory analyses of 404 participants of the health study GUNDULA, 201 men and 203 women between 30 and 80 years old, were performed to evaluate the variables for the determination of biological age. From the more than 70 laboratory variables resulting from clinical-chemical and hematologic tests and from urinalysis, less than 40 are significantly age-dependent. About half of these variables were examined by regression analysis to evaluate whether they are useful for the estimation of biological age by a laboratory index. Considerable sex differences were observed. The laboratory indexes for the participants altogether (resulting from 13 parameters) and separated for women (10 parameters) and men (8 parameters) show more variations than the biological age estimated by non-invasive parameters. In men only, there exists a significant but inverse correlation between laboratory index and relative aging rate, the difference between biological and chronological age. The results of some striking variables (e.g. dehydroepiandrosterone sulfate and others) and the results of an explorative factor analysis with regard to possible interconnections between variables and chronological age will be discussed.

Nach wie vor ist ungeklart, in welchem Ausmas die PTCA zu einem Anstieg des myokardialen Ischamiemarkers Troponin T bei Patienten mit stabiler oder instabiler Angina pectoris beitragt. Ziel dieser Studie war eine Beobachtung der Freisetzungskinetik des herzmuskelspezifischen Proteins Troponin T vor und nach PTCA bei Patienten mit instabiler und stabiler Angina pectoris.

Background Isolated unilateral corneal anaesthesia represents a very rare clinical entity. The underlying cause may be a hypoplasia of the trigeminal nerve. History and clinical findings A 7 year old otherwise healthy boy presented with mixed conjunctival injection of the left eye, fluorescein-positive punctuate epithelial keratopathy of the cornea and a central corneal ulcer OS. History revealed intermittent, painless redness of the left eye since the age of 4. Trigeminal defects caused by trauma or infection could be ruled out. Tyndall's phenomena was positive. There was no corneal sensitivity on the left side and facial sensitivity was reduced in all branches of the trigeminal nerve. All other ophthalmologic examination results were normal. Magnetic resonance tomography showed a hypoplastic left trigeminal nerve. Mesenchymal syndromes could be ruled out by neuropediatric examination. Therapy and clinical course Treatment with prednisolone and antibiotic ointment and eye patching were performed. The ulcer healed completely and artificial tear substitution was given for prophylaxis. Follow-up examinations after 4 and 6 years showed no signs of inflammation. Biomicroscopy showed only mild fluorescein-positive corneal epitheliopathy. Conclusions In cases with painless intermittent keratoconjunctivitis, sometimes associated with corneal ulceration, in early childhood, one should consider acquired or congenital trigeminal anaesthesia. This condition requires life-long corneal ulcer prophylaxis and regular ophthalmologic exams.

The S-layer of Bacillus stearothermophilus PV72/p2 shows oblique lattice symmetry and is composed of identical protein subunits with a molecular weight of 97,000. The isolated S-layer subunits could bind and recrystallize into the oblique lattice on native peptidoglycan-containing sacculi which consist of peptidoglycan of the A1gamma chemotype and a secondary cell wall polymer with an estimated molecular weight of 24,000. The secondary cell wall polymer could be completely extracted from peptidoglycan-containing sacculi with 48% HF, indicating the presence of phosphodiester linkages between the polymer chains and the peptidoglycan backbone. The cell wall polymer was composed mainly of GlcNAc and ManNAc in a molar ratio of 4:1, constituted about 20% of the peptidoglycan-containing sacculus dry weight, and was also detected in the fraction of the S-layer self-assembly products. Extraction experiments and recrystallization of the whole S-layer protein and proteolytic cleavage fragments confirmed that the secondary cell wall polymer is responsible for anchoring the S-layer subunits by the N-terminal part to the peptidoglycan-containing sacculi. In addition to this binding function, the cell wall polymer was found to influence the in vitro self-assembly of the guanidinium hydrochloride-extracted S-layer protein. Chemical modification studies further showed that the secondary cell wall polymer does not contribute significant free amino or carboxylate groups to the peptidoglycan-containing sacculi.

Purpose: To find a way to prevent or significantly reduce posterior capsule opacification (PCO) with modern phacoemulsification and in-the-bag intraocular lens (IOL) implantation. Setting: Department of Ophthalmology and Institute for Pharmaceutical Technology and Biopharmacy, Ruprecht-Karls-University of Heidelberg, Germany. Methods: We evaluated the effects of an IOL-bound sustained drug delivery system (SDDS) consisting of the carrier substance poly-DL-lactid and the drug daunorubicin or indomethacin. The system was applied to the IOL surface and implanted in rabbit eyes. At 8 weeks postoperatively, PCO wet mass was determined. Toxic and inflammatory effects were documented by histopathology. Results: The average PCO wet mass was 54.6 mg in the control group, 28.6 mg with daunorubicin, and 64.1 mg with indomethacin. Statistical analysis showed a significant reduction of PCO with daunorubicin (Mann-Whitney U-test, P = .025) and no PCO-reducing effect with indomethacin. Light microscopy of the specimens revealed mild inflammation, especially at the limbus, and some endothelial cell loss in the daunorubicin group and iris and ciliary body inflammation in the indomethacin group. Conclusion: In the rabbit eye, slow release of daunorubicin reduced PCO formation by approximately 50%. It must be determined whether the endothelial side effects are specific to the rabbit species or whether the human cornea is as sensitive. The principle of the IOL-bound SDDS and the evaluation procedure can be standardized and used for systematic tests in the future.

A method for the quantitative assessment of chitinase activity was developed. Dilution series of crude potato tuber chitinase extracts were assayed with a colorimetric microtitre plate assay. using CM-chitin-RBV as enzyme substrate. Linearity between absorbance values mea-sured (540 nm) and enzyme concentration was found to be limited to the low concentration range. where depletion of the substrate was no longer limiting. As as absorbance of 0.1 always fell within the concentration range for which absorbance-concentration linearity was valid. one unit of enzyme activity was defined as the amount of enzyme needed to yield and A of 0.1. A more reliable method for the assessment of chitinase activity was established by basing the difinition of enzyme, activity on a concentration rather than on as absorbance value. as was done previously. Using this method, differences in the rate of chitinase induction upon wounding were demonstrated for six commercial potato cultivars. Zusammenfassung Eine Methode fur die quantitative Auswertung von Chitinase-Aktivitat aus Kartoffeln ist entwickelt worden. Verdunnungsreihen von Extrakten aus rohen Kartoffelknollen wurden mit einem kolorimetrischen Mikrotiterplatten-Assay gemessen, in dem CM-Chitin-RBV als Substrat eingesetzt wurde. Eine Linearitat zwischen Absorptions-Werten (540nm) und Enzym-Konzentration wurde nur im niedrign Konzentrationsbereich festgestellt, in dem das Substrat nicht limitierent war. Da ein Absorptions-Wert von 0.1 immer in den Konzentrationsbereich fiel, in dem Linearitat zwischen Absorption und Enzym-Konzentration besteht, wurde eine Einheit Enzym-Aktivitat definiert als die Enzym-Menge, die eine Absorption von 0.1 bei 540 nm ergibt. Hierdurch wurde eine zuverlassigere Methode fur die Auswertung von Chitinase-Aktivitat entwickelt, in welcher die Definiton von Enzym-Aktivitat auf einem Konzentrations-Wert, wie dies bisher gebraucht worden ist. Mit der Verwendung dieser Methode wurden Unterschiede in dem Induktionstempo von Chitinase nach Verwundung in sechs kommerziell angepflanzten Kartoffelsorten nachgewiesen.

We report on a 53-year-old male patient who presented with severe dyspnea at rest and massive volume overload because of decompensated cor pulmonale. Furthermore he suffered from stage 3 chronic kidney disease. As there was diuretics resistance and carbon dioxide narcosis, he had to be intubated and ventilated. The massive volume overload could be successfully treated with slow continuous ultrafiltration (SCUF) with removal of a volume of 27.5 l within 3 days. The SCUF therapy is an effective and gentle method to treat even an excessive volume overload based on diuretics resistance.

Background: Present study aimed to investigate the single disseminated. tumor cells (DTC) in whole peripheral blood samples collected from patients with oral squamous cell carcinoma (OSCC) for the early detection of metastatic cells and prognosis by expression analysis of Melanoma Associated Antigen-A4 (MAGE-A4). Methods: Eighteen patients with OSCC and 14 otherwise healthy volunteers were included in this study. The QuantiGene 2:0 RNA Quantification System was used as a reagent for RNA detection and quantification, and the results were evaluated by the luminescence reader. Results: There was no DTC detected by the expression analysis of MAGE-A4 in blood samples collected from patients with OSCC. Conclusions: Detection of single DTC in peripheral whole blood samples from OSCC patients may be an effective early detection method when the suggested steps were included in the method according to the authors’ present experience.

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.

Melanoma associated-A antigens (MAGE-A) are silent in normal tissues except testis. However, they are activated in a variety of different tumors. Thus, their expression is highly specific to cancer cells. Reverse transcription-nested polymerase chain reaction (RT-nPCR) is a highly sensitive technique that has been used successfully for the detection of MAGE genes in tissue samples. The aim of the study is to analyze the expression rate of MAGE-A12 in oral squamous cell carcinoma (OSCC) using a high sensitive RT-nPCR. Total of 57 tissue samples obtained from patients with OSCC and 20 normal oral mucosal (NOM) probes of otherwise healthy volunteers were included to this study. No expression of MAGE-A12 was observed in the non-neoplastic NOM tissues. MAGE-A12 was expressed in 49.1% of the investigated tumor samples. The correlation between malignant lesion and MAGE-A12 detection was significant (p < 0.001). It is concluded that results of this study may indicate MAGE-A12 as a useful additional diagnostic marker especially for the early detection of OSCC distinguishing neoplastic transformation and detection of occult and/or rare disseminated cancer cells. In addition, MAGE-A12 expression in OSCC may also determine a new immunotherapeutic target and might be warranted to develop vaccine for OSCC.

Background Mesangial deposition of IgA (MCA) is a very rare finding in minimal change disease and has previously been considered a pure coincidence. In the U.S. and Europe only anecdotal case reports exist. To date, there has been no consensus on nomenclature and categorization of this entity. We describe 2 cases of MCA with analogue histological findings but relevant differences in clinical presentation, and we discuss the clinical implications of mesangial IgA deposition in minimal change nephrotic syndrome. Patients A 47-year-old female was admitted to hospital with nephrotic syndrome, microscopic hematuria, arterial hypertension and slight impairment of renal function 3 weeks after an unspecific upper airway infection. A 42-year-old male presented with nephrotic syndrome, microscopic hematuria, normotension and normal renal function. Both of the nephrotic syndromes were steroid-responsive and steroid-dependent. Findings The clinical presentation of the male patient was consistent with the features of minimal change glomerulopathy, whereas the female patient combined signs of minimal change disease and IgA nephropathy. Light microscopy revealed mesangial IgA immune deposits and slight mesangial hypercellularity. Electron microscopic studies of MCA patients disclose diffuse effacement of glomerular foot processes. Conclusion Our cases and a review of the literature indicate that the histological diagnosis of MCA may comprise different pathogenetic entities. From the clinical point of view, MCA has to be regarded as a minimal change nephrotic syndrome with symptomatic or asymptomatic mesangial IgA deposition. IgA deposition constitutes a risk factor for impairment of renal function and indicates a frequently relapsing course.

Background Transcatheter closure of atrial septal defects is a new and less traumatic technique than open heart surgery. In recent years, patients with a patent foramen ovale sustaining potential paradoxical embolism have also become candidates for interventional closure devices. One of the more popular occluding devices is the Amplatzer septal occluder, which, like many other occluders, is made of nitinol. Nitinol-based alloys are widely used in medical products, for example, in orthopedics and orthodontics. However, the clinical use of nitinol, which contains 55% nickel, is still controversial because of concerns about its biocompatibility. Therefore, we examined the systemic nickel release after implantation of the Amplatzer occluder. Methods and Results In 67 patients with no history of nickel sensitivity, blood samples were taken 24 hours before and 24 hours, 1, 3, and 12 months after occluder implantation. Nickel serum concentrations were measured by atomic absorption spectrometry; a value of

A theory and implementation for automatic and optimized compilation of VLSI design rule checking directives from graphically specified design rules are presented. In addition to a very comfortable user interface, this approach results in more efficient use of computer resources (a crucial asset when verifying large circuits), as exemplified with tests on design rules for a modern CMOS technology. A formal semantic description of the compilation process is given along with its systematic implementation in an expert system shell (NEXPERTObject). Thus an expert system with a sound formal basis is presented, as well as a practical evaluation of the feasibility of various programming paradigms in the language of an expert system shell. >

The author discusses the application of computer-simulation and artificial-intelligence techniques to the design of chemical plants. To illustrate the interrelationship between communications, as a generic task, and plant design, five separate layers of activities are dealt with: the decision on investment, the role of experts in plant design, the identification of isolable tasks, the tools used in plant design, and general-purpose vs. dedicated hardware. >

The laboratory analyses of 404 participants of the health study GUNDULA, 201 men and 203 women between 30 and 80 years old, were performed to evaluate the variables for the determination of biological age. From the more than 70 laboratory variables resulting from clinical-chemical and hematologic tests and from urinalysis, less than 40 are significantly age-dependent. About half of these variables were examined by regression analysis to evaluate whether they are useful for the estimation of biological age by a laboratory index. Considerable sex differences were observed. The laboratory indexes for the participants altogether (resulting from 13 parameters) and separated for women (10 parameters) and men (8 parameters) show more variations than the biological age estimated by non-invasive parameters. In men only, there exists a significant but inverse correlation between laboratory index and relative aging rate, the difference between biological and chronological age. The results of some striking variables (e.g. dehydroepiandrosterone sulfate and others) and the results of an explorative factor analysis with regard to possible interconnections between variables and chronological age will be discussed.

It is still uncertain to what extent PTCA contributes to a rise of the myocardial ischemic marker troponin T. The purpose of this study was to determine the release of troponin T in patients with unstable and stable angina pectoris pre- and post-PTCA. Serial troponin T measurements were performed in 66 patients with unstable angina (group A) and 55 patients with stable angina pectoris (group B) pre-PTCA and 4, 8 and 24 hours post-PTCA. In group A, 39 (59%) patients with unstable angina pectoris showed pathologic troponin T concentrations (troponin Tor = 0.1 ng/ml); in 27 (41%) patients already pre-PTCA the troponin T was elevated beyond the normal values. Medians of troponin T rose from initially 0.045 ng/ml pre-PTCA to a maximum of 0.21 ng/ml 8 hours post PTCA. In group B medians of troponin T were at all times within normal limits; there was no rise in the observation interval. Using the Chi-square test there were statistically significant differences between group A and B regarding the troponin T values pre- and post-PTCA. In group A medians of total creatine kinase ranging between 24 U/L and 30 U/L were to all times within normal limits. Also in group B medians of total creatine kinase were always within normal limits. Statistically significant differences between the two groups could not be shown. Our study could show a difference in the periinterventional course of the ischemic marker troponin T in patients with unstable and stable angina pectoris. The data indicate a PTCA induced reversible ischemia of the cardiac muscle cell with additional release of the cytoplasmatic bound part of troponin T in patients with unstable angina pectoris. Troponin T also appears to be a more sensitive marker of very short myocardial ischemia than creatine kinase.

Isolated unilateral corneal anaesthesia represents a very rare clinical entity. The underlying cause may be a hypoplasia of the trigeminal nerve.A 7 year old otherwise healthy boy presented with mixed conjunctival injection of the left eye, fluorescein-positive punctuate epithelial keratopathy of the cornea and a central corneal ulcer OS. History revealed intermittent, painless redness of the left eye since the age of 4. Trigeminal defects caused by trauma or infection could be ruled out. Tyndall's phenomena was positive. There was no corneal sensitivity on the left side and facial sensitivity was reduced in all branches of the trigeminal nerve. All other ophthalmologic examination results were normal. Magnetic resonance tomography showed a hypoplastic left trigeminal nerve. Mesenchymal syndromes could be ruled out by neuropediatric examination.Treatment with prednisolone and antibiotic ointment and eye patching were performed. The ulcer healed completely and artificial tear substitution was given for prophylaxis. Follow-up examinations after 4 and 6 years showed no signs of inflammation. Biomicroscopy showed only mild fluorescein-positive corneal epitheliopathy.In cases with painless intermittent keratoconjunctivitis, sometimes associated with corneal ulceration, in early childhood, one should consider acquired or congenital trigeminal anaesthesia. This condition requires life-long corneal ulcer prophylaxis and regular ophthalmologic exams.

Hintergrund Oberflachenmodifikation von Intraokularlinsen sollen die Biokompatibilitat erhohen und Zelladhasion vermindern. Die folgende Studie ging der Frage nach, ob polyfluorocarbonbeschichtete Hinterkammerlinsen (PFC-HKL) Vorteile in bezug auf die Nachstarentwicklung bieten im Vergleich zu Standard-PMMA-HKL.

In 25 patients (10 male, 15 female) with systemic sclerosis aged between 28 and 79 years the biological age was determined. Alterations in the sense of "premature aging" were observed in the mean and developed stronger in male patients. They have to be counted in a greater part on the real process of disease. Compared to a healthy reference group, the expected diminishing of hand grip strength and tendon extensibility, vital capacity and partial oxygen pressure in the arteries could be confirmed. The latter correlated to an increase in rest pulse. Auditory acuity and the condition of the teeth were also reduced. Beyond that, noteworthy differences in psychological and social parameters not presumed at the beginning point to a decrease in social activities and to psychic changes. They underline the necessity of psychological counseling of the patients.

Numbers and proportions of persons are estimated according to hearing ability and speech comprehension groups by age, sex, race, years of completed education, family income, usual activity, geographic region, place of residence, limitation of activity due to chronic conditions, annual bed days, number of physician contacts, and respondent-assessed health status. Estimates are based on data collected in household interviews during 1990-91.

Shows some aspects of VHDL for synthesis (and simulation) from a very practical view. One of the aspects addressed is the integration of VHDL into current design flows with respect to the need of graphical interfaces. A synthesis example shows the advantage of VHDL to facilitate the specification of the structure of a block's architecture together with its functional description. Comparisons to other means of circuit specification show its expressiveness to cover all practical applications. This gives an estimation of the necessary efforts to port already existing circuit models into VHDL. >

Studies to determine the biological age of a person are a major concern of gerontological research today. The use of test batteries is now a proven method, and the procedure developed in Leipzig covers 47 parameters including physical, mental, and social data. It can be seen from the related findings that this approach is suitable for dealing with specific questions in gerontology. These include the detection of medical risk factors and environmental effects, and confirmation of intervention strategies. The prime motives behind these studies then seem to be in keeping with practical requirements.