Classification of cortical microcircuits based on micro-electrode-array data from slices of rat barrel cortex

The bewildering complexity of cortical microcircuits at the single cell level gives rise to surprisingly robust emergent activity patterns at the level of laminar and columnar local field potentials (LFPs) in response to targeted local stimuli. Here we report the results of our multivariate data-analytic approach based on simultaneous multi-site recordings using micro-electrode-array chips for investigation of the microcircuitary of rat somatosensory (barrel) cortex. We find high repeatability of stimulus-induced responses, and typical spatial distributions of LFP responses to stimuli in supragranular, granular, and infragranular layers, where the last form a particularly distinct class. Population spikes appear to travel with about 33 cm/s from granular to infragranular layers. Responses within barrel related columns have different profiles than those in neighbouring columns to the left or interchangeably to the right. Variations between slices occur, but can be minimized by strictly obeying controlled experimental protocols. Cluster analysis on normalized recordings indicates specific spatial distributions of time series reflecting the location of sources and sinks independent of the stimulus layer. Although the precise correspondences between single cell activity and LFPs are still far from clear, a sophisticated neuroinformatics approach in combination with multi-site LFP recordings in the standardized slice preparation is suitable for comparing normal conditions to genetically or pharmacologically altered situations based on real cortical microcircuitry.

Realistic mean field forward predictions for the integration of co-registered EEG/fMRI

Brain activity can be measured non-invasively with functional imaging techniques. Each pixel in such an image represents a neural mass of about 105 to 107 neurons. Mean field models (MFMs) approximate their activity by averaging out neural variability while retaining salient underlying features, like neurotransmitter kinetics. However, MFMs incorporating the regional variability, realistic geometry and connectivity of cortex have so far appeared intractable. This lack of biological realism has led to a focus on gross temporal features of the EEG. We address these impediments and showcase a "proof of principle" forward prediction of co-registered EEG/fMRI for a full-size human cortex in a realistic head model with anatomical connectivity, see figure 1. MFMs usually assume homogeneous neural masses, isotropic long-range connectivity and simplistic signal expression to allow rapid computation with partial differential equations. But these approximations are insufficient in particular for the high spatial resolution obtained with fMRI, since different cortical areas vary in their architectonic and dynamical properties, have complex connectivity, and can contribute non-trivially to the measured signal. Our code instead supports the local variation of model parameters and freely chosen connectivity for many thousand triangulation nodes spanning a cortical surface extracted from structural MRI. This allows the introduction of realistic anatomical and physiological parameters for cortical areas and their connectivity, including both intra- and inter-area connections. Proper cortical folding and conduction through a realistic head model is then added to obtain accurate signal expression for a comparison to experimental data. To showcase the synergy of these computational developments, we predict simultaneously EEG and fMRI BOLD responses by adding an established model for neurovascular coupling and convolving "Balloon-Windkessel" hemodynamics. We also incorporate regional connectivity extracted from the CoCoMac database [1]. Importantly, these extensions can be easily adapted according to future insights and data. Furthermore, while our own simulation is based on one specific MFM [2], the computational framework is general and can be applied to models favored by the user. Finally, we provide a brief outlook on improving the integration of multi-modal imaging data through iterative fits of a single underlying MFM in this realistic simulation framework.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Outcome Analysis of Immediate and Delayed Conservative Breast Surgery Reconstruction With Mastopexy and Reduction Mammaplasty Techniques

Background: Bilateral mammaplasty or mastopexy is frequently used for oncoplastic objectives. However, little information has been available regarding outcome following immediate and delayed reconstruction. Method: Patients were divided into Group I (immediate reconstruction) and Group II (delayed reconstruction). Retrospective review was performed to compare complications, length of hospital stay, revision surgeries, and satisfaction. The associations between the complications with potential risk factors (timing, age, body mass index, smoking, and comorbid medical conditions) were analyzed. Results: There were a total of 144 patients with a mean follow-up of 47 months. Of the 106 patients in Group I, complications occurred in 24 (22.6%), skin necrosis was observed in 7.5%, fat necrosis in 5.6%, and 6.6% patients developed local recurrence. Mean period of hospitalization was 1.89 days. Of the 38 patients of the Group II, complications occurred in 12 (31.5%), skin necrosis was observed in 7 (18.4%), fat necrosis in 4 (10.5%), and 5.2% patients developed local recurrence. Mean period of hospitalization was 1.35 days. Increased length of hospital stay greater than 1 day (P < 0.001) and the number of revision surgeries (P = 0.043) were associated with the timing of the reconstruction. In univariate analysis, no difference between groups was found with respect to complication incidence (P = 0.275); however, after adjusting for other risk factors, the probability of complications tend to be higher for Group II (OR = 2.65; 95% confidence interval - 1.01-7.00; P = 0.049). Conclusions: On the basis of the results of our study, the probability of complications tends to be higher for delayed reconstructions, and it is demonstrated that obesity and smoking are risk factors for complications. Ultimately, these data may facilitate the provision of individualized risk information for shared medical decision-making.

Immediate reconstruction following breast-conserving surgery: Management of the positive surgical margins and influence on secondary reconstruction

The efficacy of breast-conserving Surgery for the local control of early breast cancer has been repeatedly evidenced. Although immediate reconstruction following breast-conserving Surgery has been described, little information is available regarding surgical management in reoperative settings due to positive margins. We studied the influence of intraoperatively assessed and postoperatively controlled Surgical margin status on the type of breast-conserving Surgery and report our results regarding complications in a reoperative breast reconstruction scenario. All patients were seen by a multidisciplinary team who recommended breast-conserving surgery. According to the breast volume, ptosis and tumor size/location, the patients were also evaluated by a plastic Surgeon, who recommended reconstruction with the appropriate technique. Intraoperative assessment Of Surgical margins was determined by histological examination of frozen sections. The mean follow-up time was 48 months. Two hundred and eighteen patients (88.5%) underwent breast-conserving Surgery and immediate reconstruction. Twelve (5.5%) patients had a positive tumor margin after review of the permanent section. All patients underwent re-exploration. In 1.3%, a second reconstructive technique was indicated and in 2.2% a skin-sparing mastectomy with total reconstruction was performed. Our findings support the important role of the intraoperative assessment of surgical margins and its interference in the selection of reconstruction techniques and negative margins: however, it will not guarantee complete excision of the tumor. Success depends on coordinated planning with the oncologic Surgeon and careful intraoperative management, (C) 2008 Elsevier Ltd. All rights reserved.

Immediate conservative breast surgery reconstruction with perforator flaps: New challenges in the era of partial mastectomy reconstruction?

Introduction: Although the use of local flaps in conservative breast surgery (CBS) reconstruction is a reliable technique, little information has been available regarding outcome following the use of perforator flaps. The purpose of this study is to analyze the feasibility, surgical planning and outcome following CBS reconstruction with intercostal artery perforator (ICAP) flap. Patients/methods: Thirteen patients underwent CBS reconstructions with an ICAP flap. These flaps were raised from adjacent tissue located on the lateral and thoracic region and based on perforators originating from the costal and muscular segment of the intercostal vessels. The technique was indicated in patients with small/moderate volume breasts. Results: Mean time of follow-up was 32 months. Flap complications were evaluated and information on patient satisfaction were collected. 61.5 percent had tumors located in the lower-outer quadrants and 69.2 percent had tumors measuring 2 cm or less (T1). Complications occurred in 3 patients (23%), including wound dehiscence in 2 patients and fat necrosis in one. All cases were treated by conservative approach with a good result. No flap loss or wound infection were reported. 90 percent were either satisfied or very satisfied with their result. Conclusion: The ICAP flap is a reliable technique for immediate CBS reconstruction. The technique is advantageous because it does not require the use of muscle transfer, with minimum donor site morbidity. Success depends on patient selection, coordinated planning with the oncological surgeon and careful intra-operative management. (C) 2011 Elsevier Ltd. All rights reserved.

Systemic Inflammatory Reaction After Silicone Breast Implant

Systemic inflammation after augmentation mammaplasty with modern silicone implants is not currently recognized. In a prospective controlled study, C-reactive protein and other variables were monitored, aiming to test this hypothesis in a young cohort of patients. Females (18-30 years old, BMI = 18.5-30 kg/m(2), N = 52) were consecutively recruited for breast implant (n = 24, Group I) and for abdominal liposuction (n = 28, Group II/Controls). Patients were interviewed at baseline and followed until 6 months after operation. Variables included demographic and clinical information, surgical outcome, inflammatory markers and autoantibodies. Operations were well tolerated, without surgical or infectious complications. Mean prosthesis size was 258 +/- A 21 ml (range = 220-280) and mean aspirate of liposuction was 1972 +/- A 499 ml (range = 1200-3000). Preoperative, 2-month, and 6-month C-reactive protein concentrations for breast implant patients were 1.3 +/- A 1.2, 4.8 +/- A 3.0, and 4.3 +/- A 6.4 mg/l and for liposuction 3.5 +/- A 2.7, 3.5 +/- A 2.1, and 2.2 +/- A 2.2 mg/l, respectively. Change at 2 months was significant (p = 0.001). Autoantibody investigation failed to reveal remarkable aberrations, except for anticardiolipin elevation, which was nearly symmetrical in the two groups. C-reactive protein levels increased after operation and correlated with proinflammatory and procoagulatory indices. A mild increase in anticardiolipin IgM occurred but differences between populations were lacking. Despite excellent cosmetic outcomes and lack of complications, acute phase reaction could signal ongoing immunogenicity of silicone and long-term monitoring is recommended.

Mode of operation and low-resolution structure of a multi-domain and hyperthermophilic endo-beta-1,3-glucanase from Thermotoga petrophila

1,3-beta-Glucan depolymerizing enzymes have considerable biotechnological applications including biofuel production, feedstock-chemicals and pharmaceuticals. Here we describe a comprehensive functional characterization and low-resolution structure of a hyperthermophilic laminarinase from Thermotoga petrophila (TpLam). We determine TpLam enzymatic mode of operation, which specifically cleaves internal beta-1,3-glucosidic bonds. The enzyme most frequently attacks the bond between the 3rd and 4th residue from the non-reducing end, producing glucose, laminaribiose and laminaritriose as major products. Far-UV circular dichroism demonstrates that TpLam is formed mainly by beta structural elements, and the secondary structure is maintained after incubation at 90 degrees C. The structure resolved by small angle X-ray scattering, reveals a multi-domain structural architecture of a V-shape envelope with a catalytic domain flanked by two carbohydrate-binding modules. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.

Automated two-dimensional separation flow system with electrochemical preconcentration, stripping, capillary electrophoresis and contactless conductivity detection for trace metal ion analysis

This paper describes the automation of a fully electrochemical system for preconcentration, cleanup, separation and detection, comprising the hyphenation of a thin layer electrochemical flow cell with CE coupled with contactless conductivity detection (CE-C(4)D). Traces of heavy metal ions were extracted from the pulsed-flowing sample and accumulated on a glassy carbon working electrode by electroreduction for some minutes. Anodic stripping of the accumulated metals was synchronized with hydrodynamic injection into the capillary. The effect of the angle of the slant polished tip of the CE capillary and its orientation against the working electrode in the electrochemical preconcentration (EPC) flow cell and of the accumulation time were studied, aiming at maximum CE-C(4)D signal enhancement. After 6 min of EPC, enhancement factors close to 50 times were obtained for thallium, lead, cadmium and copper ions, and about 16 for zinc ions. Limits of detection below 25 nmol/L were estimated for all target analytes but zinc. A second separation dimension was added to the CE separation capabilities by staircase scanning of the potentiostatic deposition and/or stripping potentials of metal ions, as implemented with the EPC-CE-C(4)D flow system. A matrix exchange between the deposition and stripping steps, highly valuable for sample cleanup, can be straightforwardly programmed with the multi-pumping flow management system. The automated simultaneous determination of the traces of five accumulable heavy metals together with four non-accumulated alkaline and alkaline earth metals in a single run was demonstrated, to highlight the potentiality of the system.

Bärförmåga hos lågtrafikerade vägar : Tjälrestriktioner

Denna rapport redovisar en förstudie som genomförts i syfte att belysa nuvarande hantering av tjälrestriktioner inom Vägverket, utforma ett förslag till en verksgemensam metodbeskrivning och föreslå en fortsatt verksamhet inom området för att komma tillrätta med identifierade problem och utvecklingsbehov.Syftet med denna förstudie är att:- Inventera nuvarande hantering av tjälrestriktioner vid Vägverkets regionala enheter.- Utarbeta en metodbeskrivning med uppföljningsrutiner, som i rimlig utsträckning tar hänsyn till regionernas olika förutsättningar.- Redogöra för överväganden bakom lagda förslag i metodbeskrivningen och dokumentera utgångspunkter.- Beskriva nödvändiga förändringar i berörda IT-system- Ge förslag till en arbetsgång för implementering av metoden i regionerna- Utarbeta ett förslag till fortsatt arbete med tjälrestriktioner med en grov beskrivning av kostnader och nytta.- Definiera och förtydliga begreppet tjälrestriktioner och andra betydelsefulla begrepp av betydelse för området.- Göra en grov sammanställning av näringslivets önskemål huvudsakligen genom studier av tidigare utredningar.Arbetet har genomförts genom intervjuer med ansvariga för verksamheten vid Vägverkets regioner och vid Vägverkets huvudkontor. IT-frågor har diskuterats med förvaltare av olika system och med ansvariga för utvecklingsprojekt i anslutning till området. Under arbetet har ett antal dokument insamlats och studerats.Resultatet av arbetet redovisas under rubriker som anknyter till ovanstående punkter och i bilagor.

Studie av subsynkron interaktion (SSTI) mellan ett HVDC system med spänningsstyva strömriktare och en närliggande generator

Syftet med examensarbetet är att studera den subsynkrona interaktionen (subsynchronous torsional interaktion, SSTI) mellan ett HVDC system med spänningsstyva strömriktare och en närliggande generator. Studien utförs med hjälp av datorsimuleringar och fokuserar på att studera dämpkaraktäristiken för SSTI. Studien ska visa hur faktorer såsom den överförda effektens storlek och riktning, vald driftmod och kraftsystemets kortslutningseffekt påverkar dämpkaraktäristiken. Rapporten beskriver subsynkron oscillation (SSO) och tillvägagångssättet vid en SSTI undersökning. En kort introduktion till HVDC Light ges. Studien visar att HVDC Light ökar dämpningen för det frekvensområde som är intressant. Resultaten presenteras som diagram med beräknad dämpkaraktäristik.

Vägbarriärens inverkan på snöplogning

Denna arbetsrapport presenterar en studie som utfördes i syfte att undersöka hur vägbarriärer påverkar utförandet av plogningen och till detta relaterade kostnader. Målet var att kunna identifiera och beräkna de eventuella ökningar i snöplogningskostnaderna som tillkommer på grund av vägbarriärer. Studien utfördes med hjälp av en metod som heter ”Case Study Reasearch Strategy”. Fältstudier av snöplogningen utfördes på 6 vägsträckor. Fältstudierna täckte fyra vägtyper: motorväg, mötesfria vägar, 4-fältiga vägar och målade 2+1-vägar. De barriärtyper som studerades var betongbarriär, stållineräcke, rörräcke och w-profilräcke. Plogningskvalité, arbetsmiljö, trafiksäkerhet och framkomlighet studerades med hjälp av direkta observationer av plogningsaktiviteter på fält. Genom at mäta tiden för att ploga en viss sträcka bestämdes plogningshastigheten. Resultatet visade att vägbarriärtypen påverkar varken snöplogningshastigheten eller plogningstiden nämnvärt. Vidare visade resultatet att vägbarriärtypen inte påverkar snöplogningskvaliteten längs med mittremsan. Däremot, försämras plogningskvalitén längs vägrenar med betongbarriärar eller w-profilräcken som sidobarriärer. Det är dock svårt att beräkna de kostnader som tillkommer på grund av försämrad plogningskvalité. Trots att både trafiksäkerheten och framkomligheten försämrades drastiskt under plogningen, kunde man konstatera att dessa två aspekter inte påverkades av vägbarriärtypen.

Vägprojektering för minskade drift- och underhållskostnader : Brister och möjligheter

För att kunna bygga en ny väg måste den först planeras och projekteras. Vägplanering innebär att man undersöker förutsättningarna för att bygga vägen t.ex. konsekvenser för miljö, samhälle, trafiksäkerhet, framkomlighet, tillgänglighet samt tekniska och ekonomiska förutsättningar. Vägprojektering innebär att man bestämmer vägens utformning på detaljnivå t.ex. vägsträckning, bredd, profil, vägutrustning, etc. Planering och projektering av vägar är en komplicerad process med tanke på alla komponenter som en väg består av samt alla aspekter som man måste ta hänsyn till under vägens livstid. Planerings- och projekteringsprocessen utgör en avvägning av många aspekter för att hitta den optimala lösningen. Drift- och underhållsåtgärder på vägnätet föranleds ofta av att problem uppstått på ett fåtal ställen. Kostnaden för att åtgärda dessa ställen kan uppgå till stora belopp under vägens livslängd. Med en lämpligare utformning av vägen hade dessa problem i en del fall sannolikt kunnat undvikas. Bland de aktörer, som är inblandade i planerings- och projekteringsprocessen, finns det olika åsikter om orsaken till att man inte tar tillräcklig hänsyn till drift- och underhållaspekten under planerings- och projekteringsskedet. Vissa aktörer tycker att det är projektörens kunskapsbrister som leder till att vägen får olämplig utformning avseende drift och underhåll. Andra tycker att det är en kombination av olika brister hos väghållaren. Dessa brister kan då finnas i såväl planerings- och projekteringsprocessen som i drift- och underhållsprocessen. Denna rapport presenterar resultatet för en förstudie som har utförts inom doktorandprojektet ”Vägprojektering för minskade drift- och underhållskostnader”. Syftet med förstudien var att identifiera brister och problem på övergripande nivå som leder till att man inte tar tillräcklig hänsyn till drift- och underhållsaspekten vid planerings- och projekteringsprocessen. Ett annat syfte med förstudien var att föreslå förändringsbehov inom planerings- och projekteringsprocessen genom att analysera de identifierade problemen, analysera verksamheten vid planering och projektering, analysera verksamhetens mål, formulera nya mål för verksamheten och fastställa de nödvändiga förändringsbehoven.

Svart pedagogik inom högskolevärlden : inducerad otillräcklighet bland lärarkåren ökar möjligen produktiviteten men hotar medborgarskapet

Sociologisk Forsknings digitala arkiv