Properties of functional brain networks correlate with frequency of psychogenic non-epileptic seizures.

Abnormalities in the topology of brain networks may be an important feature and etiological factor for psychogenic non-epileptic seizures (PNES). To explore this possibility, we applied a graph theoretical approach to functional networks based on resting state EEGs from 13 PNES patients and 13 age- and gender-matched controls. The networks were extracted from Laplacian-transformed time-series by a cross-correlation method. PNES patients showed close to normal local and global connectivity and small-world structure, estimated with clustering coefficient, modularity, global efficiency, and small-worldness (SW) metrics, respectively. Yet the number of PNES attacks per month correlated with a weakness of local connectedness and a skewed balance between local and global connectedness quantified with SW, all in EEG alpha band. In beta band, patients demonstrated above-normal resiliency, measured with assortativity coefficient, which also correlated with the frequency of PNES attacks. This interictal EEG phenotype may help improve differentiation between PNES and epilepsy. The results also suggest that local connectivity could be a target for therapeutic interventions in PNES. Selective modulation (strengthening) of local connectivity might improve the skewed balance between local and global connectivity and so prevent PNES events.

Evaluation of the reconstruction limits of a frequency-independent crosshole georadar waveform inversion scheme in the presence of dispersion

Waveform tomographic imaging of crosshole georadar data is a powerful method to investigate the shallow subsurface because of its ability to provide images of pertinent petrophysical parameters with extremely high spatial resolution. All current crosshole georadar waveform inversion strategies are based on the assumption of frequency-independent electromagnetic constitutive parameters. However, in reality, these parameters are known to be frequency-dependent and complex and thus recorded georadar data may show significant dispersive behavior. In this paper, we evaluate synthetically the reconstruction limits of a recently published crosshole georadar waveform inversion scheme in the presence of varying degrees of dielectric dispersion. Our results indicate that, when combined with a source wavelet estimation procedure that provides a means of partially accounting for the frequency-dependent effects through an "effective" wavelet, the inversion algorithm performs remarkably well in weakly to moderately dispersive environments and has the ability to provide adequate tomographic reconstructions.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES: It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS: This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS: Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS: Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequency.

Microsatellite instability (MSI) occurs in 10-20% of colorectal tumours and is associated with good prognosis. Here we describe the development and validation of a genomic signature that identifies colorectal cancer patients with MSI caused by DNA mismatch repair deficiency with high accuracy. Microsatellite status for 276 stage II and III colorectal tumours has been determined. Full-genome expression data was used to identify genes that correlate with MSI status. A subset of these samples (n = 73) had sequencing data for 615 genes available. An MSI gene signature of 64 genes was developed and validated in two independent validation sets: the first consisting of frozen samples from 132 stage II patients; and the second consisting of FFPE samples from the PETACC-3 trial (n = 625). The 64-gene MSI signature identified MSI patients in the first validation set with a sensitivity of 90.3% and an overall accuracy of 84.8%, with an AUC of 0.942 (95% CI, 0.888-0.975). In the second validation, the signature also showed excellent performance, with a sensitivity 94.3% and an overall accuracy of 90.6%, with an AUC of 0.965 (95% CI, 0.943-0.988). Besides correct identification of MSI patients, the gene signature identified a group of MSI-like patients that were MSS by standard assessment but MSI by signature assessment. The MSI-signature could be linked to a deficient MMR phenotype, as both MSI and MSI-like patients showed a high mutation frequency (8.2% and 6.4% of 615 genes assayed, respectively) as compared to patients classified as MSS (1.6% mutation frequency). The MSI signature showed prognostic power in stage II patients (n = 215) with a hazard ratio of 0.252 (p = 0.0145). Patients with an MSI-like phenotype had also an improved survival when compared to MSS patients. The MSI signature was translated to a diagnostic microarray and technically and clinically validated in FFPE and frozen samples.

Radio frequency identification (RFID) of dentures in long-term care facilities.

STATEMENT OF PROBLEM: The difficulty of identifying the ownership of lost dentures when found is a common and expensive problem in long term care facilities (LTCFs) and hospitals. PURPOSE: The purpose of this study was to evaluate the reliability of using radiofrequency identification (RFID) in the identification of dentures for LTCF residents after 3 and 6 months. MATERIAL AND METHODS: Thirty-eight residents of 2 LTCFs in Switzerland agreed to participate after providing informed consent. The tag was programmed with the family and first names of the participants and then inserted in the dentures. After placement of the tag, the information was read. A second and third assessment to review the functioning of the tag occurred at 3 and 6 months, and defective tags (if present) were reported and replaced. The data were analyzed with descriptive statistics. RESULTS: At the 3-month assessment of 34 residents (63 tags) 1 tag was unreadable and 62 tags (98.2%) were operational. At 6 months, the tags of 27 of the enrolled residents (50 tags) were available for review. No examined tag was defective at this time period. CONCLUSIONS: Within the limits of this study (number of patients, 6-month time span) RFID appears to be a reliable method of tracking and identifying dentures, with only 1 of 65 devices being unreadable at 3 months and 100% of 50 initially placed tags being readable at the end of the trial.

Frequency of platelet type versus type 2B von Willebrand disease. An international registry-based study.

Less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD) worldwide. Several reports have discussed the diagnostic challenge of this disease versus the closely similar disorder type 2B VWD. However, no systematic study has evaluated this dilemma globally. Over three years, a total of 110 samples/data from eight countries were analysed. A molecular approach was utilised, analysing exon 28 of the von Willebrand factor (VWF) gene, and in mutation negative cases the platelet GP1BA gene. Our results show that 48 cases initially diagnosed as putative type 2B/PT-VWD carried exon 28 mutations consistent with type 2B VWD, 17 carried GP1BA mutations consistent with a PT-VWD diagnosis, three had other VWD types (2A and 2M) and five expressed three non-previously published exon 28 mutations. Excluding 10 unaffected family members and one acquired VWD, 26 cases did not have mutations in either genes. Based on our study, the percentage of type 2B VWD diagnosis is 44% while the percentage of misdiagnosis of PT-VWD is 15%. This is the first large international study to investigate the occurrence of PT-VWD and type 2B VWD worldwide and to evaluate DNA analysis as a diagnostic tool for a large cohort of patients. The study highlights the diagnostic limitations due to unavailability/poor application of RIPA and related tests in some centres and proposes genetic analysis as a suitable tool for the discrimination of the two disorders worldwide. Cases that are negative for both VWF and GP1BA gene mutations require further evaluation for alternative diagnoses.

Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%.

AIMS: Patients with well-tolerated sustained monomorphic ventricular tachycardia (SMVT) and left ventricular ejection fraction (LVEF) over 30% may benefit from a primary strategy of VT ablation without immediate need for a 'back-up' implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: One hundred and sixty-six patients with structural heart disease (SHD), LVEF over 30%, and well-tolerated SMVT (no syncope) underwent primary radiofrequency ablation without ICD implantation at eight European centres. There were 139 men (84%) with mean age 62 ± 15 years and mean LVEF of 50 ± 10%. Fifty-five percent had ischaemic heart disease, 19% non-ischaemic cardiomyopathy, and 12% arrhythmogenic right ventricular cardiomyopathy. Three hundred seventy-eight similar patients were implanted with an ICD during the same period and serve as a control group. All-cause mortality was 12% (20 patients) over a mean follow-up of 32 ± 27 months. Eight patients (40%) died from non-cardiovascular causes, 8 (40%) died from non-arrhythmic cardiovascular causes, and 4 (20%) died suddenly (SD) (2.4% of the population). All-cause mortality in the control group was 12%. Twenty-seven patients (16%) had a non-fatal recurrence at a median time of 5 months, while 20 patients (12%) required an ICD, of whom 4 died (20%). CONCLUSION: Patients with well-tolerated SMVT, SHD, and LVEF > 30% undergoing primary VT ablation without a back-up ICD had a very low rate of arrhythmic death and recurrences were generally non-fatal. These data would support a randomized clinical trial comparing this approach with others incorporating implantation of an ICD as a primary strategy.

Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss HIV cohort study.

BACKGROUND: Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement"). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons. METHODS: Self-reported information on sexual preference, sexual partners, and condom use was collected at semi-annual visits in all participants of the prospective Swiss HIV Cohort Study from April 2007 through March 2009. Multivariable logistic regression models were fit using generalized estimating equations to investigate associations between characteristics of cohort participants and condom use. FINDINGS: A total of 7309 participants contributed to 21,978 visits. A total of 4291 persons (80%) reported sexual contacts with stable partners, 1646 (30%) with occasional partners, and 557 (10%) with stable and occasional partners. Of the study participants, 5838 (79.9%) of 7309 were receiving antiretroviral therapy, and of these, 4816 patients (82%) had a suppressed viral load. Condom use varied widely and differed by type of partner (visits with stable partners, 10,368 [80%] of 12,983; visits with occasional partners, 4300 [88%] of 4880) and by serostatus of stable partner (visits with HIV-negative partners, 7105 [89%] of 8174; visits with HIV-positive partners, 1453 [48%] of 2999). Participants were more likely to report unprotected sex with stable partners if they were receiving antiretroviral therapy, if HIV replication was suppressed, and after the publication of the "Swiss statement." Noninjection drug use and moderate or severe alcohol use were associated with unprotected sex. CONCLUSIONS: Antiretroviral treatment and plasma HIV RNA titers influence sexual behavior of HIV-positive persons. Noninjection illicit drug and alcohol use are important risk factors for unprotected sexual contacts.

Frequency-dependent sexual selection with respect to offspring fitness returns is consistent with predictions from rock-paper-scissors dynamics in the European common lizard

Genetic polymorphism can be maintained over time by negative frequency-dependent (FD) selection induced by Rock-paper-scissors (RPS) social systems. RPS games produce cyclic dynamics, and have been suggested to exist in lizards, insects, isopods, plants, and bacteria. Sexual selection is predicted to accentuate the survival of the future progeny during negative FD survival selection. More specifically, females are predicted to select mates that produce progeny genotypes that exhibit highest survival during survival selection imposed by adult males. However, no empirical evidence demonstrates the existence of FD sexual selection with respect to fitness payoffs of genetic polymorphisms. Here we tested this prediction using the common lizard Zootoca vivipara, a species with three male color morphs (orange, white, yellow) that exhibit morph frequency cycles. In a first step we tested the congruence of the morph frequency change with the predicted change in three independent populations, differing in male color morph frequency and state of the FD morph cycle. Thereafter we ran standardized sexual selection assays in which we excluded alternative mechanisms that potentially induce negative FD selection, and we quantified inter-sexual behavior. The patterns of sexual selection and the observed behavior were in line with context-dependent female mate choice and male behavior played a minor role. Moreover, the strength of the sexual selection was within the magnitude of selection required to produce the observed 3-4-year and 6-8 year morph frequency cycles at low and high altitudes, respectively. In summary, the study provides the first experimental evidence that underpins the crucial assumption of the RPS games suggested to exist in lizards, insects, isopods, and plants; namely, that sexual selection produces negative-FD selection. This indicates that sexual selection, in our study exert by females, might be a crucial driver of the maintenance of genetic polymorphisms.

Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort.

OBJECTIVES: Data on the frequency of extraintestinal manifestations (EIMs) in Crohn's disease (CD) and ulcerative colitis (UC) and analyses of their risk factors are scarce. We evaluated their prevalence and risk factors in a large nationwide cohort of inflammatory bowel disease (IBD) patients. METHODS: IBD patients from an adult clinical cohort in Switzerland (Swiss IBD cohort study) were prospectively included. Data from validated physician enrolment questionnaires were analyzed. RESULTS: A total of 950 patients were included, 580 (61%) with CD (mean age 41 years) and 370 (39%) with UC (mean age 42 years). Of these, 249 (43%) of CD and 113 (31%) of UC patients had one to five EIMs. The following EIMs were found: arthritis (CD 33%, UC 21%), aphthous stomatitis (CD 10%, UC 4%), uveitis (CD 6%, UC 4%), erythema nodosum (CD 6%, UC 3%), ankylosing spondylitis (CD 6%, UC 2%), psoriasis (CD 2%, UC 1%), pyoderma gangrenosum (CD and UC each 2%), and primary sclerosing cholangitis (CD 1%, UC 4%). Multiple logistic regression identified the following risk factors for ongoing EIM in CD: active disease (odds ratio (OR)=1.95, 95% confidence interval (CI)=1.17-3.23, P=0.01), and positive IBD family history (OR=1.77, 95% CI=1.07-2.92, P=0.025). No risk factors were identified in UC patients. CONCLUSIONS: EIMs are a frequent problem in CD and UC patients. Active disease and positive IBD family history are associated with ongoing EIM in CD patients. Identification of EIM prevalence and associated risk factors may result in increased awareness for this problem and thereby facilitating their diagnosis and therapeutic management.

Use of combined suspension laryngoscopy, flexible bronchoscopy and high frequency jet ventilation for Y-shaped airway stents delivery

La trachée et les bronches proximales sont de fins conduits subtils, ingénieusement structurés par une partie cartilagineuse antérieure résistante aux variations de pression et une partie membraneuse postérieure souple. Par leurs faibles volumes (espace mort) ils délivrent un grand pourcentage de l'air inspiré aux voies distales, puis au parenchyme pulmonaire, permettant les échanges de gaz. Cette belle harmonie respiratoire peut être rapidement mise à mal dès qu'un processus atteint ces voies respiratoires proximales, soit en les comprimant, processus sténosant, soit en affaiblissant leur structure, trachéo-bronchomalacie, soit en ouvrant leur paroi sur les structures médiastinales, fistule trachéo/broncho-médiastinales, pleurales ou autres. Le pronostic vital est alors rapidement engagé au vu de l'absolue nécessité du bon fonctionnement de ces fins conduits, une petite diminution du calibre de leurs fines lumières provoquant une baisse importante de leurs surfaces. Dans ces situations à haut potentiel de complication majeure les interventions endoscopiques pour restaurer l'intégrité de ces conduits sont alors fort risquées, et il est primordial de pouvoir les effectuer dans un cadre sécurisé au maximum. La réalisation de ces gestes par la technique décrite dans notre article « Use of combined suspension laryngoscopy, flexible bronchoscopy and high frequency jet ventilation forY-shaped airway stents delivery" permet la sécurité nécessaire à ces situations instable, en effet -la laryngoscopie en suspension expose les voies proximales en offrant un accès le plus large possible à l'arbre trachéobronchique ce qui permet l insertion de multiples instruments parfois volumineux, -la Jet ventilation assure une oxygénation et une ventilation adéquate par un fin cathéter placé soit dans le poumon sain, soit en distalité de la lésion -la bronchoscopie souple, passant au travers d'endroits exigus et courbes permet le déploiement sous vision direct, au millimètre près, de divers dispositifs. Cette association remplace avantageusement la technique traditionnelle qui insère les stents à l'aveugle, et en apnée, ce qui représente de haut risque de mauvais positionnement des stents avec des conséquences immédiates sur l'oxygénation et la ventilation souvent déjà bien altérées. Perspective et conclusion : cette technique est utile pour l'insertion des stents en Y, centraux, comme décrit dans notre article, et les indications peuvent être étendues aux stents distaux pour lesquels l'accès n'est parfois pas aisé avec le bronchoscope rigide, et pour d'autres interventions endoscopiques, laser, cryothérapie, radiofréquence ou l'insertion de nouveaux dispositifs.

Use of neuroenhancement drugs: prevalence, frequency and use expectations in Switzerland

Objective: The present study investigates the use expectations, prevalence and frequency of neuroenhancement drug (ND) use among the Swiss male population, separating college students from others. Methods: Young Swiss men were invited to participate in the Cohort Study on Substance Use Risk Factors. A total of 5,967 participants responded to questions on six types of NDs (wakefulness medication, antidepressants, Alzheimer's disease medication, Parkinson's disease medication, attention deficit-hyperactivity disorder (ADHD) medication, and beta-blockers). The frequency of use depending on five expectations (to enhance wakefulness, attention, memory, concentration and stress reduction) was analyzed for a twelve-month period. Results: (1) About 3% of the sample indicated use of at least one ND; (2) ADHD medication was the most prevalent; (3) The type of ND preferred differed depending on academic status (4). Quantitatively, over the year, college student users used ND much less frequently than other users. Conclusions: Prevalence of ND use is low in Switzerland relative to other countries such as the United States. Patterns of ND use differed depending on academic status, suggesting that while college student ND users tended to do so rarely (probably to enhance cognitive abilities for exams), non-college male users used other NDs more frequently (probably to "get high").