Search

Contains fulltext : 234463.pdf (Publisher’s version ) (Closed access) BACKGROUND: Occipital nerve stimulation (ONS) has shown promising results in small uncontrolled trials in patients with medically intractable chronic cluster headache (MICCH). We aimed to establish whether ONS could serve as an effective treatment for patients with MICCH. METHODS: The ONS in MICCH (ICON) study is an investigator-initiated, international, multicentre, randomised, double-blind, phase 3, electrical dose-controlled clinical trial. The study took place at four hospitals in the Netherlands, one hospital in Belgium, one in Germany, and one in Hungary. After 12 weeks' baseline observation, patients with MICCH, at least four attacks per week, and history of being non-responsive to at least three standard preventive drugs, were randomly allocated (at a 1:1 ratio using a computer-generated permuted block) to 24 weeks of occipital nerve stimulation at either 100% or 30% of the individually determined range between paraesthesia threshold and near-discomfort (double-blind study phase). Because ONS causes paraesthesia, preventing masked comparison versus placebo, we compared high-intensity versus low-intensity ONS, which are hypothesised to cause similar paraesthesia, but with different efficacy. In weeks 25-48, participants received individually optimised open-label ONS. The primary outcome was the weekly mean attack frequency in weeks 21-24 compared with baseline across all patients and, if a decrease was shown, to show a group-wise difference. The trial is closed to recruitment (ClinicalTrials.gov NCT01151631). FINDINGS: Patients were enrolled between Oct 12, 2010, and Dec 3, 2017. We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS. One of the 66 patients assigned to 30% ONS was not implanted and was therefore excluded from the intention-to-treat analysis. Because the weekly mean attack frequencies at baseline were skewed (median 15·75; IQR 9·44 to 24·75) we used log transformation to analyse the data and medians to present the results. Median weekly mean attack frequencies in the total population decreased from baseline to 7·38 (2·50 to 18·50; p

Alaska is a unique US state because of its large size, geographically disparate population density, and physical distance from the contiguous United States. Here, we describe a pattern of SARS-CoV-2 variant emergence across Alaska reflective of these differences. Using genomic data, we found that in Alaska the Omicron sublineage BA.2.3 overtook BA.1.1 by the week of 2022-02-27, reaching 48.5% of sequenced cases. On the contrary in the contiguous United States, BA.1.1 dominated cases for longer, eventually being displaced by BA.2 sublineages other than BA.2.3. BA.2.3 only reached a prevalence of 10.9% in the contiguous United States. Using phylogenetics, we found evidence of potential origins of the two major clades of BA.2.3 in Alaska and with logistic regression estimated how it emerged and spread throughout the state. The combined evidence is suggestive of founder events in Alaska and is reflective of how Alaska’s unique dynamics influence the emergence of SARS-CoV-2 variants.

Alaska is the largest geographic state in the United States with the lowest population density and a mix of urban centers and isolated rural communities. The differences in population dynamics in Alaska from the contiguous United States may have contributed to a unique pattern of emergence and spread of SARS-CoV-2 variants observed in early 2021. Here we examined 2,323 virus genomes from Alaska and 278,635 virus genomes from the contiguous United States collected between the first week of December 2020 through the last week of June 2021. We focused on this timeframe because of the notable emergence and spread of the SARS-CoV-2 lineage B.1.1.519 observed in Alaska. We found that this variant was consistently detected in Alaska from the end of January through June of 2021 with a peak prevalence in April of 77.9% unlike the rest of the United States with a peak prevalence of 4.6%. In Alaska, the earlier emergence of B.1.1.519 coincided with a later peak of Alpha (B.1.1.7) when compared to the rest of the United States. We also observed differences in the composition of lineages and variants over time between the two most populated regions of Alaska. Although there was a modest increase in COVID-19 cases during the peak incidence of B.1.1.519, it is difficult to disentangle how social dynamics conflated changes in COVID-19 during this time. We suggest that the viral characteristics, such as amino acid substitutions in the spike protein, and a founder effect likely contributed to the unique spread of B.1.1.519 in Alaska.

Background: A hematopoietic stem cell transplantation (HSCT) has a major impact on the functioning and perceived quality of life of patients. To describe the functioning of patients, a preliminary set of 53 categories of the International Classification of Functioning, Disability and Health (ICF) as relevant for HSCT patients has been selected earlier by a Delphi study. For the implementation of this preliminary ICF core set for patients after HSCT in clinical practice, a feasibility study was requested.Methods: A feasibility study was conducted in an explanatory mixed-methods research design. Qualitative data were collected cross-sectionally by semi-structured interviews based on specific topics related to feasibility regarding the use of the preliminary ICF core set for HSCT patients from the perspective of nurses (five in ICF-trained nurses and five regular, untrained, nurses). Quantitative data, were collected longitudinally by using a mobile health application based on ICF in which the ICF trained nurses registered HSCT patients' functioning.Results: Qualitative analysis indicated that using the preliminary ICF core set is practical and acceptable for providing information about the functioning of HSCT patients from the perspective of nurses. In addition, nurses indicated a demand for this information due to its impact on multidisciplinary meetings and clinical decision-making by involving relevant aspects of the functioning of patients. Management support, trained staff, and designated time to focus on functioning are mentioned as requirements for successful implementation. Quantitative analysis demonstrated that the most used 30% (n = 17) ICF categories are included in the preliminary ICF core set for HSCT patients (n = 24). Energy (b130) was the most used ICF category. Family relationships (d760) was the most frequently and highly positively associated ICF category.Conclusions: From the perspective of nurses, the preliminary ICF core set for HSCT patients is feasible and relevant in gaining information regarding functioning. Applying this preliminary ICF core set for HSCT patients in the anamnesis and the nursing consultations contributes to this information. Further research is needed to look at the perspective of other professionals and HSCT patients themselves.

Trigeminal autonomic cephalalgias (TACs) are a group of 4 different primary headache syndromes that have a lot of pathophysiological and clinical features in common. The 4 different TACs are: cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks and hemicrania continua. TACs are characterized by frequent, strictly unilateral, (very) intense headache attacks with ipsilateral cranial autonomic symptoms or intrinsic restlessness or both. A distinction can be made between the 4 TACs on the basis of the duration and frequency of the headache attacks. The treatment of cluster headache consists of an acute treatment and a maintenance treatment. Headache attacks in the context of paroxysmal hemicrania and hemicrania continua (almost) always respond to treatment with indomethacin. More and more neuromodulation therapies are becoming available, such as vagus nerve stimulation, stimulation and blocking of the sphenopalatine ganglion, stimulation and blocking of the occipital nerve and deep brain stimulation.

Dosing of enoxaparin for deep vein thrombosis (DVT) prophylaxis in acutely burned patients has been shown to result in anti-Xa levels below target range. We describe the first case report, to our knowledge, of a severely burned patient who, despite prophylactic dosing of enoxaparin 30 mg subcutaneously twice daily, developed an acute DVT that required high-dose enoxaparin (100 mg [1.5 mg/kg] subcutaneously every 8 hours) to maintain anti-Xa levels within the therapeutic range (0.6-1 IU/ml). Pharmacokinetic evaluations were performed using anti-Xa levels measured throughout the patient's hospital stay to validate the appropriateness of this high-dose regimen based on established therapeutic anti-Xa level ranges. These results suggest that routine anti-Xa level monitoring, regardless of enoxaparin dosing, is necessary for burn patients who are receiving enoxaparin given their hypermetabolic state following injury.

Background: Norepinephrine remains the first-line option to manage patients with circulatory shock. Limited evidence exists evaluating noncatecholamine compounds as first-line monotherapy for managing noncardiogenic shock. Objective: To compare vasopressin monotherapy with norepinephrine monotherapy for reversal of distributive and hemorrhagic shock. Methods: This was a retrospective cohort study including adult patients who were diagnosed with hypovolemic or septic shock, received fluids, and received norepinephrine or vasopressin monotherapy for at least 1 hour. Patients excluded lacked a clear diagnosis, were initiated on 2 or more vasopressors at once, or underwent cardiac surgery. The primary outcome was time to shock reversal. Secondary outcomes included mortality, lengths of stay, and safety end points. A multivariable Cox proportional hazards model was performed incorporating baseline and treatment variables. Results: A total of 85 and 160 patients were treated with vasopressin and norepinephrine, respectively. A decrease in time to shock reversal was observed in the vasopressin group (58.32 hours [95% CI, 50.88-66.00] vs 74.64 hours [95% CI, 60.96-88.32], P = 0.004). Mortality was lower in the vasopressin group (25% vs 41%, P = 0.01), and intensive care unit length of stay was longer (13 days [interquartile range, IQR = 7-19] vs 7 days [IQR = 5-9], P = 0.006). Remaining secondary outcomes were similar. The multivariable analysis revealed no difference in time to shock reversal. Conclusion and Relevance: First-line vasopressin exhibited faster time to distributive shock reversal in the unadjusted analysis but failed to maintain this difference in the multivariable analysis. These findings support safe use of vasopressin as first-line therapy or as an alternative to norepinephrine in distributive shock.

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American Association for the Advancement of Science. All rights reserved.

The creep behavior of the Ni-base Alloy 617B was analyzed at 725 °C with the focus on microstructural changes during temperature and stress exposure. High resolution electron microscopy of crept specimens reveals the precipitation behavior of secondary phases such as Cr-rich M 23 C 6 -carbides and the γ'-phase. Physical models are used to describe the Ostwald coarsening of the γ' particles and the evolution of the yield strength of the alloy. Together with the results from hot tensile tests and hardness measurements, a constitutive model for Alloy 617B has been developed. This model takes account of precipitation strengthening which is consistent with the microstructural observations, internal back stress due to dislocation hardening and material damage, all by evolutionary equations.

The Co-based alloy ASTM (Co – 28.5 wt.-% Cr – 6.3 wt.-% Mo) is widely used for medical implants, e.g. knee prostheses, and is commonly processed by investment casting. Selective laser (SLM) melting is supposed to be an efficient alternative for the production of individually designed knee implants regarding production time and production costs. The mechanical properties, in particular the fatigue strength, of the material have been studied in different states of the material. The mechanical properties of investment casted ASTM F75 and PM-SLM produced ASTM F75 were investigated. The focus in this study was on the PM-SLM material, the specimens were initially produced by selective laser melting and a part of the specimens were further processed by hot isostatic pressing (HIP). The PM-SLM material was mechanically tested in the as-SLM state as well as in the SLM+HIP state. It was found that the mechanical properties of the as-SLM material did not reach the level of the fatigue strength of as cast mat...

Surveys were collected to assess Forest Service (FS) resource managers’ perceptions, attitudes, and informational needs related to climate change and its potential impacts on forests and grasslands. Resource managers with three background types were surveyed. All participants generally considered themselves to be well-informed on climate change issues, although each resource manager group had different perceptions of climate change effects on natural resources. They shared similar views on the most potentially useful sources of information and that there was less concern at the Ranger District level about climate change. Administrative issues, including funding, were viewed by all participants as serious obstacles inhibiting agency action. Results of these surveys should provide insight for increasing science delivery efforts, providing educational opportunities, and developing guidance and training for FS resource managers. As a result, the agency can continue to provide science-based tools which assist ...

The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (i) gene-rich and SINE-rich euchromatin, (ii) gene-poor and LINE/LTR-rich heterochromatin and (iii) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show using FISH and 4C-seq technologies that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespectively of their chromosomal context thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes. ispartof: Genome Research vol:27 issue:6 pages:922-933 ispartof: location:United States status: published

Melkersson-Rosenthal syndrome (MRS) is a relatively rare syndrome characterised by the clinical triad of persisting or recurrent facial oedema, recurrent peripheral facial palsy, and a fissured tongue.A 30-year-old male patient presented with a left peripheral facial palsy spreading to the right side of the face. The left-sided facial paralysis recurred twice after initial recovery. The patient had also suffered from oedema of the lip and face, which sometimes occurred simultaneously with the paralysis, and he had always had a fissured tongue. Extensive biochemical tests, tests for infection and imaging tests revealed no abnormalities, and MRS was diagnosed. No treatment was required as the symptoms always disappeared spontaneously.Patients with MRS can present to the general practitioner, dermatologist, or ENT-specialist as well as to the neurologist. As this is a relatively unknown syndrome, the diagnosis is often made late, and it is often over-diagnosed and over-treated. There is no proven effective treatment, but systemic corticosteroids can be considered.

Introduction/Background The ACTIVLIM questionnaire was developed to measure global activity performance of neuromuscular patients (NMPs). It also has the potential to assess real life improvement resulting from new coming therapies. For this purpose, long term follow-up data are mandatory. Such data are currently absent from the literature. The aim of the present study is to compare ACTIVLIM measures of NMPs from the Belgian Neuromuscular Disease Registry (BNMDR) between years 2011 and 2015. Material and method Data from 1064 NMPs who completed the ACTIVLIM questionnaire in 2011 and 2015 were extracted from the BNMDR. RUMM 2030™ was used to obtain their global activity performance level on a unidimensional and linear measurement scale. The Wilcoxon signed rank tests and paired t-tests were used to compare ACTIVLIM measures obtained in 2011 and 2015 for the whole sample and for the 9 most prevalent diseases in BNMDR. Results In the whole sample, 64% of NMPs showed a deterioration of their activity (P ≤ 0.012; effect size (ES) = −0.32). The magnitude of deterioration was the most important for Duchenne muscular dystrophy (74% of them deteriorated; P Conclusion This is the first study focusing on activity level of NMPs using ACTIVLIM across a 5-year period. As expected, most patients showed deterioration in their activity. Among the most prevalent neuromuscular diseases, CIDP patients showed a different evolution of their global activity performance.

Cells adapt to changes in their environment by the concerted action of many different regulatory mechanisms. Examples of such mechanisms are feedback inhibition by intermediates of metabolism, covalent modification of enzymes and changes in the abundance of mRNAs and proteins. These mechanisms act in parallel at different levels in the cellular hierarchy while regulating a single process. Existing hierarchical regulation analysis determines the relative importance of these mechanisms when the cell regulates a transition from one steady-state to another. Here, the analysis is extended to the regulation of time-dependent phenomena, for which two methods are introduced and illustrated with a kinetic model incorporating transcription and translation of metabolic enzymes. © The Institution of Engineering and Technology 2006.

Clusterhoofdpijn is een relatief zeldzame, maar erg invaliderende aandoening. Het stellen van de juiste diagnose is helaas niet altijd gemakkelijk – vaak wordt in eerste instantie gedacht aan aandoeningen op het gebied van keel, neus en oren –, maar wel belangrijk om de juiste behandeling vlot in te zetten en allerlei onnodige ingrepen te voorkomen. Er bestaan goede behandelingen, zowel medicamenteus als met behulp van zuurstof, en bij de meeste patienten zijn de aanvallen vlot onder controle te krijgen. Een kleine groep chronische patienten echter is medicatieresistent, en een goed alternatief kan hen (nog) niet worden geboden.

Aim: We interrogated whether Circulating Tumor Cells (CTCs) can complement metastatic biopsies for genomic analyses. Patients and Methods: We compared single nucleotide variants (SNVs) and copy number aberrations (CNAs) identified using whole exome sequencing (WES) of DNA from frozen tumor tissue (primary/metastasis), amplified DNA from CTCs and normal DNA from 3 metastatic breast cancer (BC) patients (pts). All samples of the same patient were collected at the same timepoint. CTC isolation was performed using CellSearch and DEPArray systems followed by whole genome amplification (Ampli1 kit). WES was performed using the Illumina HiSeq2000 with 200X targeted coverage. Reads were aligned using bwa. SNVs had to be called by both Haplotype Caller (vs. reference genome) and Strelka (vs. paired normal). CNAs were determined by counting reads in 1MB windows and by comparing tumor/CTC samples with normal DNA. Pairwise concordance of CNAs profiles of different samples from the same patient was assessed using Spearman correlation (ρ). Significance of ρ differences between pts was obtained by Kruskal-Wallis test. Orthogonal validation for selected SNVs was performed. Results: We studied 3 patients from the 3 major BC subtypes, patient (pt)1 with ER-/HER2+ BC (samples collected at diagnosis, initially metastatic disease), pt2 with triple-negative BC (samples collected 2 years from diagnosis) and pt3 with ER+/HER2- BC (samples collected 8 years from diagnosis). We first compared tumor tissue and CTCs for SNVs. For pt1, of the 77 SNVs identified in the tumor, 51 were found on at least one of 12 CTCs samples. For pt2, of the 62 SNVs identified in the tumor, 19 were found on at least 1 of 11 CTCs samples. For pt3, of the 225 SNVs identified in the tumor, 48 were found on at least 1 of 3 CTCs samples. Interestingly, by increasing the number of CTCs analyzed, we increased the % of identified SNVs from synchronous tumor tissue. SNVs with high variant allele fraction (VAF) in tumor tissue were detected significantly more often in CTCs: 22% of the SNVs with VAFs 20% and >40%, respectively (p=10-12, Fisher exact test). Then, we compared tumor tissue and CTCs for CNAs. As time from diagnosis of metastatic disease to samples collection increased, we observed significantly higher heterogeneity within CTCs from the same patient (median ρ between CTCs was 86% for pt1, 84% for pt2 and 28% for pt3, p Conclusions: These data suggest that tumor tissue and single CTC exome sequencing analyses provide complementary information to map tumor heterogeneity. Further validation for potential clinical applications is needed. Citation Format: Ignatiadis M, Rothé F, Peeters D, Rouas G, Smeets D, Haan J, Lambrechts D, Campbell P, Piccart M, Voet T, Dirix L, Venet D, Sotiriou C. Exome sequencing of circulating tumor cells in metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-01-10.

IntroductionAlternating hemiplegia of childhood (AHC) is a rare disorder mainly characterized by attacks of hemiplegia and mental retardation. It has been often associated with migraine. The CACNA1A gene on chromosome 19 is involved in familial hemiplegic migraine and other episodic cerebral disorders, but also with progressive neuronal damage.MethodsWe performed mutation analysis in this gene in four AHC patients, using single strand conformation polymorphism analysis.ResultsWe found nine polymorphisms, but no mutations in any of the 47 exons.ConclusionsOther cerebral ion channel genes remain candidate genes for AHC.

Introduction In problem-based medical curricula, consideration should be given to the level of difficulty of patient cases used for training and assessment. The Amsterdam Clinical Challenge Scale (ACCS) has been developed to assess the degree of difficulty of patient cases in a systematic and reproducible manner. To determine the reliability of the instrument two research questions were addressed: (1) How many judges are required, on the basis of the total score of the ACCS, to obtain a reliable estimate of the difficulty of a single case? (2) How many cases and/or how many judges are needed to reach an acceptable level of reliability of the total score of the ACCS? Method Four judges scored 36 patient scripts reflecting a wide range of patient problems encountered in general practice. Each script was scored four times. In the reliability analysis, the generalizability theory was applied. Results The results show that the judges did, indeed, use the whole range of difficulty ratings. When the ACCS is applied to a single case, eight or more judges are needed to reach an acceptable level of reliability. When more cases are involved, fewer judges are needed; for 10 or more cases one judge will be sufficient. Conclusions Given the typical length, for example of an objective structured clinical examination, the ACCS makes it possible to provide a reliable estimate of the level of difficulty of such a test with only a limited number of judges.

Planar Stokes flow of a concentrated planar suspension of rigid cylinders is simulated using the finite-element method. A constraint condition, limiting cylinder approach to a specified distance, is applied to simulate interparticle contacts. The results of these simulations reveal a stress response and ordering of the cylinders which is similar to experimental observations of suspensions of nominally spherical particles. These results include direct observations of anisotropic structure, as well as the development of a distinct particle-phase pressure resulting from the asymmetry of interparticle contacts and the consequent developed anisotropy. A simple pair-wise interaction model is proposed for ab initio prediction of the particle-phase pressure for these planar suspensions of cylinders.

The cardiovascular safety of lubeluzole was evaluated in patients with ischemic stroke in a double-blind, placebo-controlled trial. Forty-six patients were randomized to receive a continuous daily infusion of lubeluzole 5 mg (loading dose 3.75 mg over 1 h), lubeluzole 10 mg (loading dose 7.5 mg over 1 h), or placebo for 5 days within 24 h of stroke onset. The primary measure of cardiovascular safety was the QTc interval, derived from the continuous electrocardiogram (ECG) and measured during treatment and a 2-day follow-up. Compared with placebo, neither dosage of lubeluzole had any statistically or clinically relevant effects on the QTc. Neither were there any significant differences among the three treatment groups in the area under the curve for heart rate, QT interval, QT dispersion, or QTlc. Lubeluzole did not increase the frequency of ECG abnormalities. No ventricular fibrillation, ventricular tachycardia, or torsades de pointes were observed in any of the treatment groups. During this trial, 3 patients in the placebo group and 2 patients in the lubeluzole 5-mg group died. There were no deaths in the lubeluzole 10-mg group. Adverse experiences were similar in all three treatment groups except that superficial thrombophlebitis was more frequent in the lubeluzole 10-mg group. In doses to 10 mg/day, lubeluzole has a favorable cardiovascular safety profile, as demonstrated by the lack of clinically relevant effects on heart rate, QT, QTc, and QTlc, and it was well tolerated by patients with ischemic stroke.

0.1. Aim of Ms research. In recent years, the formal elements of Dutch Intonation have been laid down in two comprehensive models ('t Hart, Collier and Cohen 1990, Gussenhoven and Rietveld 1992). With these two formal models at our disposal, the stage seems set for further explorations, notably of the relationship between form and function. The present study focused on acoustic correlates of a major functional contrast', viz. the contrast between declarativity and interrogativity, two functions featuring prominently in everyday communication. Generally speaking, declarative utterances are used for making announcements, relating events, stating conclusions and so on. By contrast, interrogative utterances make a direct appeal to a listener for a reply. While declarative utterances usually have the most basic form of clause available in a language, interrogativity may be marked by special syntactic and/or lexical means, in particular by Inversion of subject and finite verb or by the presence of a question word. These, however, are by no means the sole indicators of the contrast between declarativity and interrogativity. It is assumed that Intonation, also, plays an important role, notably in interrogative utterances lacking the lexico/syntactic devices of interrogativity ('declarative questions'). Thus, if Dutch interrogativity has intonational characteristics of its own, it seems plausible for such characteristics to be stronger as lexico/ syntactic marking for interrogativity is weaker. For the purpose of our research, declarativity and interrogativity are seen as forming a continuum, with Statements (S) at one extreme end, and declarative questions (D) at the other; in between are the wh-questions (W, marked both by question word and Inversion) and yes/no questions (Y, marked by Inversion only). Our objectives were (i) to determine to what extent the acoustic properties of interrogativity· are different from those of declarativity, and (ii) to pinpoint possible acoustic differences among the question types themselves. Also, we wished to ascertain to what extent such acoustic characteristics still need to be incorporated into the two formal models of Dutch Intonation mentioned above.

A diffusion model of metal surface modification by plasma nitriding has been developed. This model takes into account the erosion effects at the plasma/solid interface occurring due to the ion bombardment of the surface. For constant sputtering rate, which is the usual situation during plasma nitriding, the growth of the sub-layers is well described by the analytical expressiong(t) =g 0,f −1 (t/t 0), whereg(t) is the sub-layer thickness at timet,g 0 andt 0 are parameters which depend on the treated material and plasma characteristics,f −1 is the inverse of the function — In(1 - x) + x), 0 ≤x ≤ 1. Under negligible erosion effects, the expression forg(t) reduces to the parabolic law. The diffusion zone (substratum) growth does not follow the parabolic law as well. However, the deviation occurs after long plasma nitriding time. The model can be used for experimentally determining the effective diffusion coefficients and the erosion rate during plasma nitriding of metal surfaces.

Heparin coating of an extracorporeal circuit for cardiopulmonary bypass improves the hemocompatibility of the circuit and reduces the inflammatory response of the body. It has not been established, however, that heparin coating also improves postoperative hemostasis. We therefore performed a study in 30 patients who underwent a routine coronary artery bypass graft operation subjected to cardiopulmonary bypass with an uncoated (control) or a heparin-coated extracorporeal circuit (Duraflo II). We found significantly higher plasma levels of heparin in the Duraflo II group. However, we found no significant differences between the two groups with regard to other parameters of activation of the fibrinolytic and coagulation systems and to activation of platelets. Postoperative blood loss and donor blood transfusions were reduced in the Duraflo II group but not to a statistically significant extent. We conclude that heparin coating of an extracorporeal circuit improves anticoagulation but does not significantly reduce platelet activation, fibrinolysis, postoperative blood loss, and donor blood transfusions in routine coronary bypass operations.

The Cognitive Network Management System (CNMS) is a joint research initiative between Rockwell Collins and the Institute for Human Machine Cognition that aims to provide automated, policy-based real time network management for complex MANET networks. CNMS is a lightweight and efficient policy management framework designed to mitigate the need for centralized network management, reduce operator hands-on time, and increase network reliability. CNMS provides the necessary reasoning and enforcement mechanisms for the on-demand management of network topology and communication resources. Furthermore, it supports fully distributed policy learning mechanisms that enable networked devices to adapt at run-time to unanticipated network conditions and application requirements by creating and distributing learned policies. In this paper we describe the CNMS architecture and functionality. We focus our discussions on the CNMS architecture and policy learning mechanisms. Policy learning in CNMS is intrinsically distributed, and based on network performance observations for the refinement of contexts, and actions. In this paper we describe two examples for policy adaptation, one based on link capacity monitoring, and one based on adaptive frequency hoping strategies for interference mitigation. We then present some results from NS-3 evaluations of these two examples. CNMS has been implemented and tested in a two channel wireless testbed using the Universal Software Radio Peripheral (USRP) [1] and 802.11 wireless networking communication. We briefly discuss the testbed and describe some of our experimental results followed by a brief discussion of our findings, and recommendations for future work.

The Envoy Framework addresses a need for computer-based assistants or agents that operate in conjunction with users' existing applications, helping them perform tedious, repetitive, or time-consuming tasks more easily and efficiently. Envoys carry out missions for users by invoking envoy-aware applications called operatives and inform users of mission results via envoy-aware applications called informers. The distributed, open architecture developed for Envoys is derived from an analysis of the best characteristics of existing agent systems. This architecture has been designed as a model for how agent technology can be seamlessly integrated into the electronic desktop. It defines a set of application programmer's interfaces so that developers may convert their software to envoy-aware applications. A subset of the architecture described in this paper has been implemented in an Envoy Framework prototype.

Depressive disorders are a prevalent comorbidity in restless legs syndrome (RLS). Although similar prevalence rates of comorbid depression can be found in other diseases, the association between RLS and depression is particularly complex due to the RLS-related sleep disorders. It is also clinically important that according to findings derived mainly from case studies many antidepressant agents can aggravate RLS symptoms. The presence of comorbid depression influences therapy outcome in general and should therefore be taken into account. So far, there is no evidence-based systematic research concerning diagnosis and treatment process, and no recommendations exist for the treatment of affective disorders in RLS. In the present work, the clinical relevance of depression in RLS and antidepressive treatment in RLS symptoms is discussed and a therapeutic algorithm (evidence level C) for the treatment of depression in RLS is provided.

Trigeminal autonomic cephalalgias (TACs) include cluster headache, paroxysmal hemicranias and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCTs). --Because they are rare, it is often difficult to recognise TACs in practice. Hallmarks of TACs include the strictly unilateral pain near the eye or temple, the accompanying autonomic symptoms, and the specific pattern in the timing of the attacks. --The TAC subtypes differ in the duration and frequency of attacks. Differentiating TAC subtypes is important because it affects the treatment approach. --In rare cases, TAC results from an underlying structural disorder. Neuroimaging (cerebral MRI) is advised in all patients with TAC.

A possible relation between migraine and epilepsy has been a matter of debate for many decades. Clinical, epidemiological and therapeutic similarities may be coincidental and are no proof of a common aetiological background. However, a genetically determined dysfunction of ion channels seems to point to a common underlying mechanism for both paroxysmal disorders. For example, mutations in the three known genes for familial hemiplegic migraine can cause epilepsy. It is likely that the development of specific drugs aimed at restoring ion-channel function and/or related cellular signalling pathways might benefit patients with epilepsy as well as those with migraine. This review will briefly summarize the clinical, epidemiological, pathophysiological and therapeutic similarities between migraine and epilepsy. Most attention will be paid to the genetic relationship between these two paroxysmal disorders.

Contains fulltext : 70291.pdf (Publisher’s version ) (Closed access) Of the 18 missense mutations in the CACNA1A gene, which are associated with familial hemiplegic migraine type 1 (FHM1), only mutations S218L, R583Q and T666M were identified in more than two independent families. Including the four novel families presented here, of which two represent de novo cases, the R1347Q mutation has now been identified in six families. A genotype-phenotype comparison of R1347Q mutation carriers revealed a wide clinical spectrum ranging from (trauma triggered) hemiplegic migraine with and without ataxia, loss of consciousness and epilepsy. R1347Q is the third most frequent mutation in hemiplegic migraine patients and should therefore be screened with priority for confirmation of clinical diagnosis. This study clearly demonstrates that the availability of multiple families better reflects the full clinical spectrum associated with FHM1 mutations.

Proximal and distal latency as well as motor nerve conduction velocity were determined in the following nerves in 100 subjects (71 healthy subjects and 29 patients): tibial, peroneal, ulnar, median. All neurographic parameters were obtained by means of simultaneous recording with surface and concentric needle electrodes and compared with one another