Feasibility of a Composite Measure of Pulmonary Vascular Impedance and Application to Patients with Chronic RV Failure Post LVAD Implant.

Pulmonary vascular impedance (PVZ) describes RV afterload in the frequency domain and has not been studied extensively in LVAD patients. We sought to determine (1) feasibility of calculating a composite (c)PVZ using standard of care (SoC), asynchronous, pulmonary artery pressure (PAP) and flow (PAQ) waveforms; and (2) if chronic right ventricular failure (RVF) post-LVAD implant was associated with changes in perioperative cPVZ.PAP and PAQ were obtained via SoC procedures at three landmarks: T(1), Retrospectively, pre-operative with patient conscious; and T(2) and T(3), prospectively with patient anesthetized, and either pre-sternotomy or chest open with LVAD, respectively. Additional PAP's were taken at T(4), following chest closure; and T(5), 4-24 h post chest closure. Harmonics (z) were calculated by Fast Fourier Transform (FFT) with cPVZ(z) = FFT(PAP)/FFT(PAQ). Total pulmonary resistance Z(0); characteristic impedance Zc, mean of cPVZ(2-4); and vascular stiffness PVS, sum of cPVZ(1,2), were compared at T(1,2,3) between +/-RVF groups.Out of 51 patients, nine experienced RVF. Standard hemodynamics and changes in cPVZ-derived parameters were not significant between groups at any T.In conclusion, cPVZ calculated from SoC measures is possible. Although data that could be obtained were limited it suggests no difference in RV afterload for RVF patients post-implant. If confirmed in larger studies, focus should be placed on cardiac function in these subjects.

[Ethical decision making in dental care for frail older people]. / Ethische kwesties in de mondzorg voor kwetsbare ouderen.

Vurnerable older people often need intensive preventive and curative oral health care. However, their physical and cognitive decline does not always allow for lege artis implementation of dental treatments. This causes practical problems often with related moral issues. Including these moral issues in planning and implementation will make oral healthcare more effective and will also alleviate moral pressure on oral healthcare providers. Mostly the moral issues relate to every day ethics, which can be solved by all persons involved collectively, in open consultation and with an ethics of care approach. This means aiming at 'doing the right thing in the right way', including all the relevant aspects of the person of the patient and his/her environment. To achieve this, oral health care should be embedded in the overall care process for the elderly and care providers should feel involved with the older person and have reflective skills.

Angle-resolved photoelectron spectroscopy and scanning tunnelling spectroscopy studies of the endohedral fullerene Li@C60.

Gas phase photoelectron spectroscopy (Rydberg Fingerprint Spectroscopy), TDDFT calculations and low temperature STM studies are combined to provide detailed information on the properties of the diffuse, low-lying Rydberg-like SAMO states of isolated Li@C60 endohedral fullerenes. The presence of the encapsulated Li is shown by the calculations to produce a significant distortion of the lowest-lying S- and P-SAMOs that is dependent on the position of the Li inside the fullerene cage. Under the high temperature conditions of the gas phase experiments, the Li is mobile and able to access different positions within the cage. This is accounted for in the comparison with theory that shows a very good agreement of the photoelectron angular distributions, allowing the symmetry of the observed SAMO states to be identified. When adsorbed on a metal substrate at low temperature, a strong interaction between the low-lying SAMOs and the metal substrate moves these states to energies much closer to the Fermi energy compared to the situation for empty C60 while the Li remains frozen in an off-centre position.

Racial and ethnic differences among children with new-onset autoimmune Type 1 diabetes.

AIM: To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes. METHODS: We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.7 (0.3-18.1) years, the mean (sd) BMI percentile was 69.7 (25.4) and 48.3% of the cohort were girls. The cohort comprised 57.3% non-Hispanic white, 20.5% Hispanic and 14.8% African-American children, and 7.4% were of other, mixed or unknown race. RESULTS: The Hispanic subgroup, compared with non-Hispanic white subgroup, had a higher mean (sd) C-peptide level [0.82 (1.62) vs 0.55 (0.47) ng/ml; P=0.004), and a greater proportion of children with elevated BMI (overweight or obesity; 49.6% vs 32.5%; P<0.001) and diabetic ketoacidosis (51.8% vs 38.2%; P=0.006). The African-American group had a higher mean (sd) glucose level [24.4 (12.8) vs 21.4 (10.7) mmol/l; P=0.017], a greater proportion of children with ketoacidosis (56.7% vs 38.2%; P=0.001), a greater proportion with elevated BMI (52.9% vs 32.5%; P<0.001), and a lower proportion of children at pre-pubertal stage (49.0% vs 61.6%; P=0.01), and tended to have higher C-peptide levels [0.65 (0.59) vs 0.55 [0.47] ng/ml; P=0.079) compared with the non-Hispanic white children. The differences in C-peptide levels compared with non-Hispanic white children persisted for Hispanic (P=0.01) but not African-American children (P=0.29) after adjustment for age, sex, BMI, ketoacidosis, glucose, Tanner stage and autoantibody number. CONCLUSION: At the onset of paediatric autoimmune Type 1 diabetes, Hispanic, but not African-American children had higher C-peptide levels, after adjustment for potential confounders, compared with non-Hispanic white children. These findings suggest that ethnicity may contribute to the heterogeneity of Type 1 diabetes pathogenesis, with possible implications for intervention.

[Leptospirosis in French Guiana and the Guiana shield: Current knowledge in 2016]. / La leptospirose en Guyane française et sur le bouclier des Guyanes. État des connaissances en 2016.

Leptospirosis is a cosmopolitan zoonosis caused by bacteria of the genus Leptospira. Whether the distribution is worldwide, the hot and humid climate of the tropics is particularly conducive to its expansion. In most French overseas departments and territories, leptospirosis is considered as a public health problem. In French Guiana, a French department located in the northeastern part of the Amazon rainforest, it is supposed to be rare. The objective of this review was to make an inventory of the knowledge on human and animal leptospirosis in French Guiana and neighboring countries. A comprehensive search was conducted through the indexed and informal medical literature in English, French, Spanish and Portuguese. Thus, respectively ten and four publications were identified on human and animal leptospirosis in French Guiana, published between 1940 and 1995 in the form of case reports or case series. The publications concerning this disease in the other countries of the Guiana Shield, eastern Venezuela, Guyana, Suriname, and Brazilian state of Amapá, also scarce or nonexistent. However recent data from the French National Centre of leptospirosis showed a recent and sudden increase in the number of cases in the department, probably partly due to the development of diagnostic tools such as Elisa IgM serology. It is likely that leptospirosis is a neglected disease in the region, due to the lack of diagnostic tools readily available, the lack of knowledge of the local clinicians on this disease and the existence of many other pathogens with similar clinical presentation such as malaria, arboviruses and Q fever and Amazonian toxoplasmosis. The establishment of more large-scale studies on animal and human leptospirosis is necessary and urgent to know the true burden of this disease in our region.

Cerebrospinal fluid volume in neonates undergoing spinal anaesthesia: a descriptive magnetic resonance imaging study.

BACKGROUND: Spinal anaesthesia (SA) reduces the risk of postoperative apnoea after general anaesthesia in neonates. In 30% of patients, however, the duration of anaesthesia provided does not allow completion of surgery. When compared with term infants, formerly preterm neonates experience a shorter duration of anaesthesia after SA. A difference in the cerebrospinal fluid (CSF) volume between those two populations could explain this difference, but this has never been investigated. The study was designed to evaluate the relationship between the spinal CSF volume and patient characteristics in neonates. METHODS: Sixty-seven neonates, aged 30-60 weeks postconception, were included in this study. Their spinal CSF volumes were calculated using magnetic resonance imaging, and these volumes were plotted individually against sex, term at birth, birth weight, current gestational age, civil age, and weight. Correlations between CSF volume and these variables were investigated. RESULTS: Fifty-four neonates completed the study. The CSF volume was found to be closely and linearly correlated with weight and postconceptional age. The relationship between spinal CSF volume and weight can be described as follows: CSF volume (ml)=1.94 weight (kg)+0.13. The CSF volume was not correlated with sex, weight, or term at birth, nor with civil age. CONCLUSIONS: The amount of spinal CSF in neonates can be estimated as 2 ml kg(-1) in both term and formerly preterm neonates. A difference in the CSF volume between them does not provide an explanation for a shorter duration of SA in the latter. Our findings reinforce weight-adjusted dosage of SA in neonates.

Two-dimensional self-assembly of benzotriazole on an inert substrate.

The ultra-high vacuum (UHV) room temperature adsorption of benzotriazole (BTAH), a well-known corrosion inhibitor for copper, has been investigated on the pristine Au(111) surface using a combination of surface sensitive techniques. The dimensionality of the molecule is reduced from the 3D crystal structure to a 2-dimensional surface confinement, which induces the formation of hydrogen bonded 1-dimensional molecular chains consisting of alternating pro-S and pro-R enantiomers mainly. The 0-dimensional system is characteristic of gas-phase BTAH, which undergoes a tautomeric equilibrium, with consequences for the resulting adsorbed species. The balance between hydrogen bonding, inter-chain van der Waals interactions and surface-molecule interactions, and the correlation with the dimensionality of the system, are discussed in light of the experimental results and a computational description of the observed features.

Favorable Bridging Therapy Based on DWI-FLAIR Mismatch in Patients with Unclear-Onset Stroke.

BACKGROUND AND PURPOSE: Standard selection criteria for revascularization therapy usually exclude patients with unclear-onset stroke. Our aim was to evaluate the efficacy and safety of revascularization therapy in patients with unclear-onset stroke in the anterior circulation and to identify the predictive factors for favorable clinical outcome. MATERIALS AND METHODS: We retrospectively analyzed 41 consecutive patients presenting with acute stroke with unknown time of onset treated by intravenous thrombolysis and/or mechanical thrombectomy. Only patients without well-developed fluid-attenuated inversion recovery changes of acute diffusion lesions on MR imaging were enrolled. Twenty-one patients were treated by intravenous thrombolysis; 19 received, simultaneously, intravenous thrombolysis and mechanical thrombectomy (as a bridging therapy); and 1 patient, endovascular therapy alone. Clinical outcome was evaluated at 90 days by using the mRS. Mortality and symptomatic intracranial hemorrhage were also reported. RESULTS: Median patient age was 72 years (range, 17-89 years). Mean initial NIHSS score was 14.5 ± 5.7. Successful recanalization (TICI 2b-3) was assessed in 61% of patients presenting with an arterial occlusion, symptomatic intracranial hemorrhage occurred in 2 patients (4.9%), and 3 (7.3%) patients died. After 90 days, favorable outcome (mRS 0-2) was observed in 25 (61%) patients. Following multivariate analysis, initial NIHSS score (OR, 1.43; 95% CI, 1.13-1.82; P = .003) and bridging therapy (OR, 37.92; 95% CI, 2.43-591.35; P = .009) were independently associated with a favorable outcome at 3 months. CONCLUSIONS: The study demonstrates the safety and good clinical outcome of acute recanalization therapy in patients with acute stroke in the anterior circulation and an unknown time of onset and a DWI/FLAIR mismatch on imaging. Moreover, bridging therapy versus intravenous thrombolysis alone was independently associated with favorable outcome at 3 months.

Patient selection for stroke endovascular therapy--DWI-ASPECTS thresholds should vary among age groups: insights from the RECOST study.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the benefits of endovascular intervention in large-vessel occlusion strokes, depending on age class. MATERIALS AND METHODS: A clinical management protocol including intravenous treatment and mechanical thrombectomy was instigated in our center in 2009 (Prognostic Factors Related to Clinical Outcome Following Thrombectomy in Ischemic Stroke [RECOST] study). All patients with acute ischemic stroke with an anterior circulation major-vessel occlusion who presented within 6 hours were evaluated with an initial MR imaging examination and were analyzed according to age subgroups (younger than 50 years, 50-59 years, 60-69 years, 70-79 years; 80 years or older). The mRS score at 3 months was the study end point. RESULTS: One hundred sixty-five patients were included in the analysis. The mean age was 67.4 years (range, 29-90 years). The mean baseline NIHSS score was 17.24 (range, 3-27). The mean DWI-derived ASPECTS was 6.4. Recanalization of TICI 2b/3 was achieved in 80%. At 3 months, 41.72% of patients had a good outcome, with a gradation of prognosis depending on the age subgroup and a clear cutoff at 70 years. Only 19% of patients older than 80 years had a good outcome at 3 months (mean ASPECTS = 7.4) with 28% for 70-79 years (mean ASPECTS = 6.8), but 58% for 60-69 years (mean ASPECTS = 6), 52% for 50-59 years (mean ASPECTS = 5.91), and 72% for younger than 50 years (mean ASPECTS = 6.31). In contrast, the mortality rate was 35% for 80 years and older, and 26% for 70-79 versus 5%-9% for younger than 70 years. CONCLUSIONS: The elderly may benefit from thrombectomy when their ischemic core volume is low in comparison with younger patients who still benefit from acute recanalization despite larger infarcts. Stroke volume thresholds should, therefore, be related and adjusted to the patient's age group.

Aptamer BAX 499 mediates inhibition of tissue factor pathway inhibitor via interaction with multiple domains of the protein.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a multidomain protein that negatively regulates the coagulation cascade. TFPI inhibits the tissue factor (TF)-activated factor VII-activated FX (FXa) complex during TF-mediated coagulation initiation. The aptamer BAX 499 binds specifically to TFPI and inhibits its function, mediating a procoagulant effect in both in vitro and in vivo models of hemophilia. OBJECTIVES: This study sought to identify the regions of TFPI that are critical for BAX 499 binding, and to determine how binding mediates aptamer inhibition of TFPI. METHODS AND RESULTS: In vitro biochemical methods were used to evaluate the BAX 499 interaction with and inhibition of TFPI. Binding experiments indicated that the full-length TFPI protein is required for tight aptamer binding. Binding-competition experiments implicated the Kunitz 1, Kunitz 3 and C-terminal domains of TFPI in aptamer binding, a finding that is supported by hydrogen-deuterium exchange experiments, and indicated that aptamer and FXa can bind simultaneously to TFPI. In enzymatic assays, BAX 499 inhibited TFPI in a manner that is distinct from domain-specific antibodies, and aptamer inhibitory activity is reduced in the presence of the TFPI cofactor protein S. CONCLUSIONS: These studies demonstrate that BAX 499 binds to TFPI via multiple domains of the protein in a manner that is distinct from other TFPI inhibitors, mediating a mechanism of inhibition that does not involve direct competition with FXa. With this unique inhibitory mechanism, BAX 499 provides a useful tool for studying TFPI biology in health and disease.

Inhibition of tissue factor pathway inhibitor by the aptamer BAX499 improves clotting of hemophilic blood and plasma.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor-initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI. OBJECTIVES: The aim of the study was to examine the concentration-dependent augmentation of clotting by BAX499. METHODS: Whole blood clot formation was quantified by rotational thromboelastometry and thromboelastography, and thrombin generation in platelet-poor plasma was assessed with the calibrated automated thrombogram, in samples from patients with congenital hemophilia A (N=55) and B (N=11), patients with acquired hemophilia A (N=1), and healthy controls (N=37). RESULTS: BAX499 significantly improved clotting of samples from hemophilic patients in a concentration-dependent manner, resulting in clotting profiles in samples from patients with severe hemophilia that were similar to those of healthy controls. CONCLUSION: BAX499 improved ex vivo clotting parameters in blood and plasma from patients with hemophilia A and B with different severity of disease, and also in a patient with acquired hemophilia. These results further support the contention that anti TFPI strategies may be an effective treatment for hemophilic patients.

Improvement of spatial fibrin formation by the anti-TFPI aptamer BAX499: changing clot size by targeting extrinsic pathway initiation.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a major regulator of clotting initiation and a promising target for pro- and anticoagulation therapy. The aptamer BAX499 (formerly ARC19499) is a high-affinity specific TFPI antagonist designed to improve hemostasis. However, it is not clear how stimulation of coagulation onset by inactivating TFPI will affect spatial and temporal clot propagation. OBJECTIVE: To examine the BAX499 effect on clotting in a spatial, reaction-diffusion experimental system in comparison with that of recombinant activated factor VII (rVIIa). METHODS: Clotting in plasma activated by immobilized tissue factor (TF) was monitored by videomicroscopy. RESULTS: BAX499 dose-dependently improved coagulation in normal and hemophilia A plasma activated with TF at 2 pmole m(-2) by shortening lag time and increasing clot size by up to ~2-fold. The effect was TFPI specific as confirmed by experiments in TFPI-depleted plasma with or without TFPI supplementation. Clotting improvement was half-maximal at 0.7 nm of BAX499 and reached a plateau at 10 nm, remaining there at concentrations up to 1000 nm. The BAX499 effect decreased with TF surface density increase. RVIIa improved clotting in hemophilia A plasma activated with TF at 2 or 20 pmole m(-2) , both by shortening lag time and increasing spatial velocity of clot propagation; its effects were strongly concentration dependent. CONCLUSIONS: BAX499 significantly improves spatial coagulation by inhibiting TFPI in a spatially localized manner that is different to that observed with rVIIa.

[Dissertations 25 years after date 24. Barriers to effective periodontal care]. / Proefschriften 25 jaar na dato 24. Belemmeringen bij effectieve parodontale behandeling.

In the thesis 'Barriers to effective periodontal care, published in 1984, an investigation was described on professional periodontal care lagging behind the development of periodontology. The objectives of the investigation were to assess whether dentists were treating periodontal disease as a behavioural problem using effective communication techniques, and whether serious periodontal disease had such low frequency that dentists had not the opportunity to become experienced in recognizing the disease. It was concluded that serious periodontal disease had a low frequency and was not influenced by communication on periodontal care. After 25 years, these conclusions are still valid: the percentage of risk patients is still 5-10% and the correlation between seriousness of periodontal disease and periodontal care provided is still limited. Not all dentists do have affinity to periodontal care, but they do have affinity to practical aspects, such as removing dental calculus deposits. A classification of obvious recognizable diseases and treatments would make periodontal care more manageable for dentists.

Strong electron correlations in the normal state of the iron-based FeSe0.42Te0.58 superconductor observed by angle-resolved photoemission spectroscopy.

We investigate the normal state of the "11" iron-based superconductor FeSe0.42Te0.58 by angle-resolved photoemission. Our data reveal a highly renormalized quasiparticle dispersion characteristic of a strongly correlated metal. We find sheet dependent effective carrier masses between approximately 3 and 16m{e} corresponding to a mass enhancement over band structure values of m{*}/m{band} approximately 6-20. This is nearly an order of magnitude higher than the renormalization reported previously for iron-arsenide superconductors of the "1111" and "122" families but fully consistent with the bulk specific heat.

Formation and diffusion of water dimers on rutile TiO2(110).

From an interplay of time-lapsed high resolution scanning tunneling microscopy and density functional theory calculations we reveal the formation and diffusion of water dimers on hydrated rutile TiO2(110)-(1x1) surfaces, i.e., surfaces containing OH_{br} groups. At temperatures between approximately 150 and approximately 210 K water monomers diffusing along the Ti troughs were found to form stable water dimers that diffuse faster than the water monomers. An H bond mediated rollover mechanism operating for the water dimers explains the experimental findings.

Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779.

BACKGROUND: von Willebrand factor (VWF) has a role in both hemostasis and thrombosis. Platelets adhere to damaged arteries by interactions between the VWF A1-domain and glycoprotein Ib receptors under conditions of high shear. This initial platelet binding event stimulates platelet activation, recruitment, and activation of the clotting cascade, promoting thrombus formation. OBJECTIVE: To characterize the inhibitory activity of a VWF inhibitory aptamer. METHODS: Using in vitro selection, aptamer stabilization, and conjugation to a 20-kDa poly(ethylene glycol), we generated a nuclease-resistant aptamer, ARC1779, that binds to the VWF A1-domain with high affinity (K(D) approximately 2 nM). The aptamer was assessed for inhibition of VWF-induced platelet aggregation. In vitro inhibition of platelet adhesion was assessed on collagen-coated slides and injured pig aortic segments. In vivo activity was assessed in a cynomolgus monkey carotid electrical injury thrombosis model. RESULTS AND CONCLUSION: ARC1779 inhibited botrocetin-induced platelet aggregation (IC90 approximately 300 nM) and shear force-induced platelet aggregation (IC95 approximately 400 nM). It reduced adhesion of platelets to collagen-coated matrices and formation of platelet thrombi on denuded porcine arteries. ARC1779 also inhibited the formation of occlusive thrombi in cynomolgus monkeys. We have discovered a novel anti-VWF aptamer that could have therapeutic use as an anti-VWF agent in the setting of VWF-mediated thrombosis.