The “pain matrix” in pain-free individuals

Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals,1,2 and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery. The pain-specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed,3,4 remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”4 Demonstrating the nonspecificity of the pain matrix requires ruling out the presence of pain when highly salient sensory stimuli are presented. In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI. Loss-of-function SCN9A mutations in these individuals abolishes sensory neuron sodium channel Nav1.7 activity, resulting in pain insensitivity through an impaired peripheral drive that leaves tactile percepts fully intact.5 This allows complete experimental disambiguation of sensory responses and painful sensations

Wheat seed embryo excision enables the creation of axenic seedlings and Koch’s postulates testing of putative bacterial endophytes

Early establishment of endophytes can play a role in pathogen suppression and improve seedling development. One route for establishment of endophytes in seedlings is transmission of bacteria from the parent plant to the seedling via the seed. In wheat seeds, it is not clear whether this transmission route exists, and the identities and location of bacteria within wheat seeds are unknown. We identified bacteria in the wheat (Triticum aestivum) cv. Hereward seed environment using embryo excision to determine the location of the bacterial load. Axenic wheat seedlings obtained with this method were subsequently used to screen a putative endophyte bacterial isolate library for endophytic competency. This absence of bacteria recovered from seeds indicated low bacterial abundance and/or the presence of inhibitors. Diversity of readily culturable bacteria in seeds was low with 8 genera identified, dominated by Erwinia and Paenibacillus. We propose that anatomical restrictions in wheat limit embryo associated vertical transmission, and that bacterial load is carried in the seed coat, crease tissue and endosperm. This finding facilitates the creation of axenic wheat plants to test competency of putative endophytes and also provides a platform for endophyte competition, plant growth, and gene expression studies without an indigenous bacterial background.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Performance Improvement of Tomographic Image Reconstruction Based on DSP Processors

This paper presents the use of a multiprocessor architecture for the performance improvement of tomographic image reconstruction. Image reconstruction in computed tomography (CT) is an intensive task for single-processor systems. We investigate the filtered image reconstruction suitability based on DSPs organized for parallel processing and its comparison with the Message Passing Interface (MPI) library. The experimental results show that the speedups observed for both platforms were increased in the same direction of the image resolution. In addition, the execution time to communication time ratios (Rt/Rc) as a function of the sample size have shown a narrow variation for the DSP platform in comparison with the MPI platform, which indicates its better performance for parallel image reconstruction.

The CATH Hierarchy Revisited-Structural Divergence in Domain Superfamilies and the Continuity of Fold Space

This paper explores the structural continuum in CATH and the extent to which superfamilies adopt distinct folds. Although most superfamilies are structurally conserved, in some of the most highly populated superfamilies (4% of all superfamilies) there is considerable structural divergence. While relatives share a similar fold in the evolutionary conserved core, diverse elaborations to this core can result in significant differences in the global structures. Applying similar protocols to examine the extent to which structural overlaps occur between different fold groups, it appears this effect is confined to just a few architectures and is largely due to small, recurring super-secondary motifs (e.g., alpha beta-motifs, alpha-hairpins). Although 24% of superfamilies overlap with superfamilies having different folds, only 14% of nonredundant structures in CATH are involved in overlaps. Nevertheless, the existence of these overlaps suggests that, in some regions of structure space, the fold universe should be seen as more continuous.

Accurate and Precise Zinc Isotope Ratio Measurements in Urban Aerosols

We developed an analytical method and constrained procedural boundary conditions that enable accurate and precise Zn isotope ratio measurements in urban aerosols. We also demonstrate the potential of this new isotope system for air pollutant source tracing. The procedural blank is around 5 ng and significantly lower than published methods due to a tailored ion chromatographic separation. Accurate mass bias correction using external correction with Cu is limited to Zn sample content of approximately 50 ng due to the combined effect of blank contribution of Cu and Zn from the ion exchange procedure and the need to maintain a Cu/Zn ratio of approximately 1. Mass bias is corrected for by applying the common analyte internal standardization method approach. Comparison with other mass bias correction methods demonstrates the accuracy of the method. The average precision of delta(66)Zn determinations in aerosols is around 0.05% per atomic mass unit. The method was tested on aerosols collected in Sin Paulo City, Brazil. The measurements reveal significant variations in delta(66)Zn(Imperial) ranging between -0.96 and -0.37% in coarse and between -1.04 and 0.02% in fine particular matter. This variability suggests that Zn isotopic compositions distinguish atmospheric sources. The isotopic light signature suggests traffic as the main source. We present further delta(66)Zn(Imperial) data for the standard reference material NIST SRM 2783 (delta 66Z(Imperial) = 0.26 +/- 0.10%).

Tailored Media for Homogeneous Cellulose Chemistry: Ionic Liquid/Co-Solvent Mixtures

Co-solvents can minimize two of the major problems associated with the use of ionic liquids (ILs) as solvents for homogeneous derivatization of cellulose: high viscosity and limited miscibility with non-polar reagents or reaction products. Thus, the effects of 18 solvents and 3 binary solvent mixtures on cellulose solutions in three ILs were systematically studied with respect to the solution phase behavior. The applicable limits of these mixtures were evaluated and general guidelines for the use of co-solvents in cellulose chemistry could be advanced: Appropriate co-solvents should have EN T values (normalized empirical polarity) > 0.3, very low ``acidity`` (alpha < 0.5), and relatively high ""basicity`` (beta >= 0.4). Moreover, novel promising co-solvents and binary co-solvent mixtures were identified.

Pappersmakulatur vid Bobergs Tryckeri AB - orsaker och förbättringsförslag

Pappersmakulatur uppstår i tryckpressarna, men orsakerna finns i företagets alla funktioner. För ett framgångsrikt förbättringsarbete med att minska makulaturen krävs därför att all personal är engagerad.Examensarbetet utfördes på Bobergs Tryckeri AB i Falun, ett familjeägt företag med 60 anställda, som producerar personifierad direktreklam och blanketter. Syftet var att undersöka hur pappersmakulaturen kan minska och målet var att hitta orsaker samt ge förslag på åtgärder för att minska den.Genom intervjuer med personalen kartlades produktionssprocessen och utifrån det utarbetades förbättringsförslag. Exempel på förbättringsförslag är att kontinuerligt mäta och rapportera makulaturen, förbättra kommunikationen mellan avdelningarna och utveckla färgstyrningen. Litteraturstudier och kontakter med nyckelpersoner inom branschorganisationer och andra liknande företag, var till stor hjälp i arbetet. Fördjupningsdelen i projektet har sin grund i boken The Printer’s Guide to Waste Reduction av Tim Dalton.

Studier på nytt fordon för transport av skogsflis

Högskolan Dalarna har i samarbete med Naturbränsle i Mellansverige AB genomfört studier på ett nytt fordon för transport av skogsflis. Eftersom fordonet är utrustat med kran och skopa innebär det att flisskördaren kan tippa flisen direkt på marken, eller på en i förväg utlagd duk för att förhindra att föroreningar (grus, sten etc.) följer med vid lastningen av fordonet. Pro¬jektet har finansierats av EU-strukturfond Mål 2 Norra samt genom naturabidrag från deltag¬ande företag. Studier har även genomförts på lastväxlarfordon med container för att jämförel¬ser skall kunna göras mellan de båda fordonstyperna. Studierna omfattar sammanlagt tjugo lass, varav tio lass med det nya fordonet, fem lass med lastväxlarfordon och två containrar och fem lass med lastväxlarfordon och tre containrar. Den sammanlagda transportvolymen uppgick till 1 940 m3s. Tidsstudier har också genomförts på flisskördarens arbete, eftersom det i vissa delar är direkt beroende på vilket vidaretransportfordon som används. I de fall vidaretransporten sker med lastväxlarfordon vägs flisen innan den tippas i containern (en åtgärd för att fordonet inte skall överskrida tillåten lastvikt). Om lastvikten inte är begränsande genomför flisskördaren vissa åtgärder för att lastvolymen i respektive container skall kunna maximeras (t.ex. utjämning och viss packning av flisen med hjälp av kranen). I det fall vidaretransporten sker med det nya fordonet behöver flisskördaren inte väga flisen eftersom bilen är försedd med kranvåg. Där¬emot tillkommer andra arbetsuppgifter för flisskördaren, t.ex. preparering av avlägget (snö¬packning, sten- och buskröjning) samt hantering och utläggning av dukar.Arbetstiden för vidaretransporten är i huvudsak beroende av transportsträckan och medel¬transporthastigheten. När lastväxlarfordon används är arbetstiden dessutom beroende av last¬volymen (antalet containrar och deras volym) samt om tippmöjligheter endast finns på drag¬fordonet (containrar på släp måste omlastas till dragfordon innan flisen kan tippas) eller om tippmöjligheter finns på såväl dragbil som släp. Om släpet inte kan medföras till uppställ¬ningsplatsen för containrarna (p.g.a. alltför smal och kurvig väg eller utrymmesbrist för vänd¬ning av fordonsekipaget) påverkas även arbetstiden av avståndet mellan containrar och släp samt av medelhastigheten vid ”skotning” av containrar till och från släpet.Medelhastigheten vid transport var i stort sett densamma för de båda fordonstyperna. För last¬växlarfordonet med två containrar tog den totala arbetstiden (inklusive tom- och lasskörning) mellan 1,70 och 2,99 G0-tim per lass, vilket motsvarar en prestation på mellan 32 och 52 m3s/G0-tim. Arbetstiden för lastning och lossning varierade mellan 0,87 och 1,09 G0-tim/lass, eller 0,009-0,011 G0-tim/m3s (medeltal 0,98 G0-tim/lass, eller 0,011 G0-tim/m3s), vilket motsvarar en prestation på mellan 87 och 107 m3s/G0-tim.För fordonet med tre containrar tog den totala arbetstiden (inklusive tom- och lasskörning) mellan 2,40 och 3,53 G0-tim per lass, vilket motsvarar en prestation på mellan 30 och 45 m3s/ G0-tim. Arbetstiden för lastning och lossning varierade mellan 1,07 och 1,62 G0-tim/ lass, eller 0,011-0,016 G0-tim/m3s (medeltal 1,33 G0-tim/lass, eller 0,013 G0-tim/m3s), vilket mot¬svarar en prestation på mellan 64 och 89 m3s/G0-tim.Den totala arbetstiden för det nya fordonet (inklusive tom- och lasskörning) varierade mellan 2,11 och 5,08 G0-tim per lass, vilket motsvarar en prestation på mellan 18 och 45 m3s/G0-tim. Arbetstiden för lastning och lossning varierade mellan 0,96 och 1,46 G0-tim per lass, eller 0,01-0,02 G0-tim/m3s (medeltal 1,22 G0-tim/lass, eller 0,013 G0-tim/m3s), vilket mot¬svarar en prestation på mellan 65 och 94 m3s/G0-tim.