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The study highlights the transboundary nature of tuberculosis (TB) in alpacas and the failure of current ante-mortem testing protocols (the tuberculin skin and Enferplex Camelid TB tests) to identify TB-free alpaca herds and individuals for export. Our research and the available literature indicate that the alpaca (Vicugna pacos) is extremely susceptible to Mycobacterium bovis infection, and that testing periodicity fails to take into account that animals do not manifest disease symptoms for a long time. The skin test failed to identify Mycobacterium bovis infection in two alpacas prior to their movement from the UK to Poland. The animals were purchased by a breeding centre in Poland, and were then shown at an international animal exhibition. The last owner of the alpacas before their deaths from TB bought the infected animals unwittingly in order to run rehabilitation activities with disabled children on his farm.

Abstract Background To improve nutritional assessment and care pathways in the acute care setting, it is important to understand the indicators that may predict nutritional risk. Informed by a review of systematic reviews, this project engaged stakeholders to prioritise and reach consensus on a list of evidence based and clinically contextualised indicators for identifying malnutrition risk in the acute care setting. Methods A modified Delphi approach was employed which consisted of four rounds of consultation with 54 stakeholders and 10 experts to reach consensus and refine a list of 57 risk indicators identified from a review of systematic reviews. Weighted mean and variance scores for each indicator were evaluated. Consistency was tested with intra class correlation coefficient. Cronbach's alpha was used to determine the reliability of the indicators. The final list of indicators was subject to Cronbach’s alpha and exploratory principal component analysis. Results Fifteen indicators were considered to be the most important in identifying nutritional risk. These included difficulty self-feeding, polypharmacy, surgery and impaired gastro-intestinal function. There was 82% agreement for the final 15 indicators that they collectively would predict malnutrition risk in hospital inpatients. Conclusion The 15 indicators identified are supported by evidence and are clinically informed. This represents an opportunity for translation into a novel and automated systems level approach for identifying malnutrition risk in the acute care setting.

Psychiatric hospitalizations and emergency department (ED) visits are costly, stigmatizing, and often ineffective. Given the immune and kynurenine activation in bipolar disorder (BD) and schizophrenia, as well as the immune-modulatory effects of statins, we aimed to compare the relative risk (RRs) of psychiatric hospitalizations and ED visits between individuals prescribed lipophilic vs. hydrophilic statins vs. no statins. We hypothesized (a) reduced rates of hospitalization and ER utilization with statins versus no statins and (b) differences in outcomes between statins, as lipophilia increases the capability to penetrate the blood–brain barrier with potentially beneficial neuroimmune, antioxidant, neuroprotective, neurotrophic, and endothelial stabilizing effects, and, in contrast, potentially detrimental decreases in brain cholesterol concentrations leading to serotoninergic dysfunction, changes in membrane lipid composition, thus affecting ion channels and receptors.

Objective: Volumetric abnormalities of basal ganglia have been associated with attention deficit hyperactivity disorder (ADHD), especially in boys. To specify localization of these abnormalities, large deformation diffeomorphic metric mapping (LDDMM) was used to examine the effects of ADHD, sex, and their interaction on basal ganglia shapes.Method: The basal ganglia (caudate, putamen, globus pallidus) were manually delineated on magnetic resonance imaging from 66 typically developing children (35 boys) and 47 children (27 boys) with ADHD. LDDMM mappings from 35 typically developing children were used to generate basal ganglia templates. Shape variations of each structure relative to the template were modeled for each subject as a random field using Laplace-Beltrami basis functions in the template coordinates. Linear regression was used to examine group differences in volumes and shapes of the basal ganglia.Results: Boys with ADHD showed significantly smaller basal ganglia volumes compared with typically developing boys, and LDDMM revealed the groups remarkably differed in basal ganglia shapes. Volume compression was seen bilaterally in the caudate head and body and anterior putamen as well as in the left anterior globus pallidus and right ventral putamen. Volume expansion was most pronounced in the posterior putamen. No volume or shape differences were revealed in girls with ADHD.Conclusions: The shape compression pattern of basal ganglia in boys with ADHD suggests that ADHD-associated deviations from typical brain development involve multiple frontal-subcortical control loops, including circuits with premotor, oculomotor, and prefrontal cortices. Further investigations employing brain-behavior analyses will help to discern the task-dependent contributions of these circuits to impaired response control that is characteristic of ADHD. [ABSTRACT FROM AUTHOR]

In this paper we obtain a sharp (improved) lower bound on the locating-total domination number of a graph, and show that the decision problem for the locating-total domination is NP-complete.

For an integer k ≥ 1, we say that a (finite simple undirected) graph G is k-distance-locally disconnected, or simply k-locally disconnected if, for any x ∈ V (G), the set of vertices at distance at least 1 and at most k from x induces in G a disconnected graph. In this paper we study the asymptotic behavior of the number of edges of a k-locally disconnected graph on n vertices. For general graphs, we show that this number is Θ(n2) for any fixed value of k and, in the special case of regular graphs, we show that this asymptotic rate of growth cannot be achieved. For regular graphs, we give a general upper bound and we show its asymptotic sharpness for some values of k. We also discuss some connections with cages.

We compared manual and automated segmentations of the hippocampus in patients with mesial temporal sclerosis. This comparison showed good precision of the deformation-based automated segmentations. Copyright © 2000 by W.B. Saunders Company [ABSTRACT FROM AUTHOR]

Abstract Background Currently the American Red Cross requires that individuals renew their cardiopulmonary resuscitation (CPR) certification annually; this often requires a 4- to 8-hour refresher course. Those trained in CPR often show a decrease in essential knowledge and skills within just a few months after training. New electronic means of communication have expanded the possibilities for delivering CPR refreshers to members of the general public who receive CPR training. The study’s purpose was to determine the efficacy of three novel CPR refreshers - online website, e-mail and text messaging – for improving three outcomes of CPR training - skill retention, confidence for using CPR and intention to use CPR. These three refreshers may be considered “novel” in that they are not typically used to refresh CPR knowledge and skills. Methods The study conducted two randomized clinical trials of the novel CPR refreshers. A mailed brochure was a traditional, passive refresher format and served as the control condition. In Trial 1, the refreshers were delivered in a single episode at 6 months after initial CPR training. In Trial 2, the refreshers were delivered twice, at 6 and 9 months after initial CPR training, to test the effect of a repeated delivery. Outcomes for the three novel refreshers vs. the mailed brochure were determined at 12 months after initial CPR training. Results Assignment to any of three novel refreshers did not improve outcomes of CPR training one year later in comparison with receiving a mailed brochure. Comparing outcomes for subjects who actually reviewed some of the novel refreshers vs. those who did not indicated a significant positive effect for one outcome, confidence for performing CPR. The website refresher was associated with increased behavioral intent to perform CPR. Stated satisfaction with the refreshers was relatively high. The number of episodes of refreshers (one vs. two) did not have a significant effect on any outcomes. Conclusions There was no consistent evidence for the superiority of novel refreshers as compared with a traditional mailed brochure, but the low degree of actual exposure to the materials does not allow a definitive conclusion. An online web-based approach seems to have the most promise for future research on electronic CPR refreshers.

Abstract Background Meiotic maps are a key tool for comparative genomics and association mapping studies. Next-generation sequencing and genotyping by sequencing are speeding the processes of SNP discovery and the development of new genetic tools, including meiotic maps for numerous species. Currently there are limited genetic resources for sockeye salmon, Oncorhynchus nerka. We develop the first dense meiotic map for sockeye salmon using a combination of novel SNPs found in restriction site associated DNA (RAD tags) and SNPs available from existing expressed sequence tag (EST) based assays. Results We discovered and genotyped putative SNPs in 3,430 RAD tags. We removed paralogous sequence variants leaving 1,672 SNPs; these were combined with 53 EST-based SNP genotypes for linkage mapping. The map contained 29 male and female linkage groups, consistent with the haploid chromosome number expected for sockeye salmon. The female map contains 1,057 loci spanning 4,896 cM, and the male map contains 1,118 loci spanning 4,220 cM. Regions of conservation with rainbow trout and synteny between the RAD based rainbow trout map and the sockeye salmon map were established. Conclusions Using RAD sequencing and EST-based SNP assays we successfully generated the first high density linkage map for sockeye salmon.

Abstract Background The management of background corticosteroid therapy in rheumatology clinical trials poses a major challenge. We describe the consensus methodology used to design an algorithm to standardize changes in corticosteroid dosing during the Randomized Placebo Phase Study of Rilonacept in Systemic Juvenile Idiopathic Arthritis Trial (RAPPORT). Methods The 20 RAPPORT site principal investigators (PIs) and 4 topic specialists constituted an expert panel that participated in the consensus process. The panel used a modified Delphi Method consisting of an on-line questionnaire, followed by a one day face-to-face consensus conference. Consensus was defined as ≥ 75% agreement. For items deemed essential but when consensus on critical values was not achieved, simple majority vote drove the final decision. Results The panel identified criteria for initiating or increasing corticosteroids. These included the presence or development of anemia, myocarditis, pericarditis, pleuritis, peritonitis, and either complete or incomplete macrophage activation syndrome (MAS). The panel also identified criteria for tapering corticosteroids which included absence of fever for ≥ 3 days in the previous week, absence of poor physical functioning, and seven laboratory criteria. A tapering schedule was also defined. Conclusion The expert panel established consensus regarding corticosteroid management and an algorithm for steroid dosing that was well accepted and used by RAPPORT investigators. Developed specifically for the RAPPORT trial, further study of the algorithm is needed before recommendation for more general clinical use.

Abstract Background Physiotherapy research concerning interventions for children with CP is often focused on collecting evidence of the superiority of particular therapeutic methods or treatment modalities. Articulating and documenting the use of theory, instrumentation and research design and the assumptions underlying physiotherapy research interventions are important. Physiotherapy interventions focusing on children with Cerebral Palsy should, according to the literature, be based on a functional and environmental perspective with task-specific functional activity, motor learning processes and Family-Centred Service i.e. to enhance motor ability and improve capacity so that the child can perform the tasks necessary to participate actively in everyday life. Thus, it is important to coordinate the norms and values of the physiotherapist with those of the family and child. The aim of this study was to describe how physiotherapists’ experiences physiotherapy interventions for children with CP in scientific physiotherapy publications written by physiotherapists. Methods A qualitative phenomenographic approach was used. Twenty- one scientific articles, found in PubMed, strategically chosen according to year of publication (2001–2009), modality, journals and country, were investigated. Results Three qualitatively different descriptive categories were identified: A: Making it possible a functional-based intervention based on the biopsychosocial health paradigm, and the role of the physiotherapist as collaborative, interacting with the child and family in goal setting, intervention planning and evaluation, B: Making it work an impairment-based intervention built on a mixed health paradigm (biomedical and biopsychosocial), and the role of the physiotherapist as a coach, leading the goal setting, intervention planning and evaluation and instructing family members to carry out physiotherapist directed orders, and; C: Making it normal an impairment-based intervention built on a biomedical health paradigm, and the role of the physiotherapist as an authoritative expert who determine goals, intervention planning and evaluation. Conclusions Different paradigms of health and disability lead to different approaches to physiotherapy which influence the whole intervention process regarding strategies for the assessment and treatment, all of which influence Family-Centred Service and the child’s motor learning strategies. The results may deepen physiotherapists’ understanding of how different paradigms of health influence the way in which various physiotherapy approaches in research seek to solve the challenge of CP.

Abstract Background Hypoglycemia is a common complication of diabetes treatment. This paper describes symptoms, predecessors, consequences and medications associated with the first episode of severe hypoglycemia among ACCORD participants with type 2 diabetes, and compares these between intensive (Int: goal A1C Methods Information about symptoms, antecedents, and consequences was collected at the time participants reported an episode of severe hypoglycemia. Data on medications prescribed during the clinical trial was used to determine the association of particular diabetes drug classes and severe hypoglycemia. Results The most frequently reported symptoms in both glycemia group were weakness/fatigue (Int 29%; Std 30%) and sweating (Int 26%; Std 27%), followed by confusion/disorientation (Int 22%; Std 29%) and shakiness (Int 21%; Std 19%). Approximately half of all events were preceded by a variation in food intake (Int 48%; Std 58%). The most common consequences were confusion (Int 37%; Std 34%), loss of consciousness (Int 25%; Std 25%), and hospitalization (Int 18%; Std 24%). The highest rates of hypoglycemia were found among those participants treated with insulin only (Int 6.09/100 person yrs; Std 2.64/100 person yrs) while the lowest were among those prescribed oral agents only (Int 1.93/100 person yrs; Std 0.20/100 person yrs). Conclusions Severe hypoglycemia episodes were frequently preceded by a change in food intake, making many episodes potentially preventable. Symptoms of confusion/disorientation and loss of consciousness were frequently seen. The highest rates of hypoglycemia were seen with prescription of insulin, either alone or in combination with other medications. Clinical Trial Registration Number: NCT00000620

Abstract Background 2'-Fucosyllactose (2-FL) is a functional oligosaccharide present in human milk which protects against the infection of enteric pathogens. Because 2-FL can be synthesized through the enzymatic fucosylation of lactose with guanosine 5′-diphosphate (GDP)-l-fucose by α-1,2-fucosyltransferase (FucT2), an 2-FL producing Escherichia coli can be constructed through overexpressing genes coding for endogenous GDP- l-fucose biosynthetic enzymes and heterologous fucosyltransferase. Results The gene for FucT2 from Helicobacter pylori was introduced to the GDP- l-fucose producing recombinant E. coli BL21 star(DE3) strain. However, only small amount of 2-FL was produced in a batch fermentation because the E. coli BL21star(DE3) strain assimilated lactose instead of converting to 2-FL. As an alternative host, the E. coli JM109(DE3) strain which is incapable of assimilating lactose was chosen as a 2-FL producer. Whole cell biosynthesis of 2-FL from lactose was investigated in a series of batch fermentations using various concentrations of lactose. The results of batch fermentations showed that lactose was slowly assimilated by the engineered E. coli JM109(DE3) strain and 2-FL was synthesized without supplementation of another auxiliary sugar for cell growth. A maximum 2-FL concentration of 1.23 g/l was obtained from a batch fermentation with 14.5 g/l lactose. The experimentally obtained yield (g 2-FL/g lactose) corresponded to 20% of the theoretical maximum yield estimated by the elementary flux mode (EFM) analysis. Conclusions The experimental 2-FL yield in this study corresponded to about 20% of the theoretical maximum yield, which suggests further modifications via metabolic engineering of a host strain or optimization of fermentation processes might be carried out for improving 2-FL yield. Improvement of microbial production of 2-FL from lactose by engineered E. coli would increase the feasibility of utilizing 2-FL as a prebiotic in various foods.

Abstract Background Amyloid accumulation in the brain parenchyma is a hallmark of Alzheimer's disease (AD) and is seen in normal aging. Alterations in cerebrospinal fluid (CSF) dynamics are also associated with normal aging and AD. This study analyzed CSF volume, production and turnover rate in relation to amyloid-beta peptide (Aβ) accumulation in the aging rat brain. Methods Aging Fischer 344/Brown-Norway hybrid rats at 3, 12, 20, and 30 months were studied. CSF production was measured by ventriculo-cisternal perfusion with blue dextran in artificial CSF; CSF volume by MRI; and CSF turnover rate by dividing the CSF production rate by the volume of the CSF space. Aβ40 and Aβ42 concentrations in the cortex and hippocampus were measured by ELISA. Results There was a significant linear increase in total cranial CSF volume with age: 3-20 months (p < 0.01); 3-30 months (p < 0.001). CSF production rate increased from 3-12 months (p < 0.01) and decreased from 12-30 months (p < 0.05). CSF turnover showed an initial increase from 3 months (9.40 day-1) to 12 months (11.30 day-1) and then a decrease to 20 months (10.23 day-1) and 30 months (6.62 day-1). Aβ40 and Aβ42 concentrations in brain increased from 3-30 months (p < 0.001). Both Aβ42 and Aβ40 concentrations approached a steady state level by 30 months. Conclusions In young rats there is no correlation between CSF turnover and Aβ brain concentrations. After 12 months, CSF turnover decreases as brain Aβ continues to accumulate. This decrease in CSF turnover rate may be one of several clearance pathway alterations that influence age-related accumulation of brain amyloid.

Abstract Background There have been increases in the obesity and overweight rates in Australian children over the past 25 years and it has been suggested that sugar sweetened beverages (SSB) have played a role in this increase. Objective The objectives of this study were to: (1) examine SSB intakes in the 2007 Australian Children's Nutrition and Physical Activity Survey (2) relate SSB intake to rates of overweight and obesity, socio-economic status (SES), TV viewing time, and activity levels and (3) compare 2007 SSB intakes with data from the 1995 National Nutrition Survey. Design A computer assisted 24 h dietary recall in 4,400 children aged 2-16 years was performed. Results In the 2007 survey 47% of all children reported drinking SSBs with 25% consuming sugar sweetened soft drinks on the day of the survey. The mean consumption of soft drink was 436 g/d/consumer. Activity levels were unrelated to SSB consumption. Television viewing was positively related to soft drink consumption with a difference of 55 g/day from bottom to top tertile of time spent TV viewing (p = 0.015) in children aged 9-16 years. 55% of SSB consumption occurred at home and 10% occurred at school. Lower SES status was associated with a greater prevalence of SSB consumption- 30% for the lowest SES quartile vs 19% in the highest quartile. The proportion of overweight who consumed SSBs (which excludes 100% fruit) was not different from the non-overweight children although the proportion of SSB consumers in the 6% of children who were obese was significant compared with the non-overweight children (59% vs 47%, p < 0.05). In the 2007 survey 23% of children were overweight (17%) or obese (6%) while in the 1995 survey this figure was 21%. The proportion of children consuming SSBs in 1995 and 2007 for selected age groups were: 2-3 years - 25.8% and 12.8% respectively and 4-7 years - 33.6% and 20.5% respectively (p < 0.001 for both). Conclusions This cross-sectional data set provides evidence that SSB consumption for Australian children is still high despite the decrease since 1995 in some age groups. It provides little support to conclude that overweight in children is currently being driven by excessive SSB consumption although it may be factor in some obese children. Conclusions are limited by the cross sectional nature of the study.

Abstract Background Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD). There is an accumulation of amyloid-beta peptides (Aβ) in both the AD brain and the normal aging brain. Clearance of Aβ from the brain occurs via active transport at the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). With increasing age, the expression of the Aβ efflux transporters is decreased and the Aβ influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Aβ transporters at the choroid plexus (CP) epithelium as a function of aging was the subject of this study. Methods This project investigated the changes in expression of the Aβ transporters, the low density lipoprotein receptor-related protein-1 (LRP-1), P-glycoprotein (P-gp), LRP-2 (megalin) and the receptor for advanced glycation end-products (RAGE) at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC) to measure transporter protein in isolated rat CP. Results There was an increase in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Aβ42 concentration in the CP, as measured by quantitative IHC, was associated with these Aβ transporter alterations. Conclusions Age-dependent alterations in the CP Aβ transporters are associated with a decrease in Aβ42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Aβ clearance in aging.

Abstract Background Neuropeptides may have considerable potential in the treatment of acute and chronic neurological diseases. Encapsulated genetically engineered cells have been suggested as a means for sustained local delivery of such peptides to the brain. In our experiments, we studied human mesenchymal stem cells which were transfected to produce glucagon-like peptide-1 (GLP-1). Methods Cells were packed in a water-permeable mesh bag containing 400 polymeric microcapsules, each containing 3000 cells. The mesh bags were either transplanted into the subdural space, into the brain parenchyma or into the cerebral ventricles of the cat brain. Mesh bags were explanted after two weeks, and cell viability, as well as GLP-1 concentration in the cerebrospinal fluid (CSF), was measured. Results Viability of cells did not significantly differ between the three implantation sites. However, CSF concentration of GLP-1 was significantly elevated only after ventricular transplantation with a maximum concentration of 73 pM (binding constant = 70 pM). Conclusions This study showed that ventricular cell-based delivery of soluble factors has the capability to achieve concentrations in the CSF which may become pharmacologically active. Despite the controversy about the pharmacokinetic limitations of ventricular drug delivery, there might be a niche in this for encapsulated cell biodelivery of soluble, highly biologically-effective neuropeptides of low molecular weight like GLP-1.

Abstract Objective Although electronic medical records (EMRs) have facilitated care for children with juvenile idiopathic arthritis (JIA), analyses of treatment outcomes have required paper based or manually re-entered data. We have started EMR discrete data entry for JIA patient visits, including joint examination and global assessment, by physician and patient. In this preliminary study, we extracted data from the EMR to Xenobase™ (TransMed Systems, Inc., Cupertino, CA), an application permitting cohort analyses of the relationship between global assessment to joint examination and subtype. Methods During clinic visits, data were entered into discrete fields in ambulatory visit forms in the EMR (EpicCare™, Epic Systems, Verona, WI). Data were extracted using Clarity Reports, then de-identified and uploaded for analyses to Xenobase™. Parameters included joint examination, ILAR diagnostic classification, physician global assessment, patient global assessment, and patient pain score. Data for a single visit for each of 160 patients over a 2 month period, beginning March, 2010, were analyzed. Results In systemic JIA patients, strong correlations for physician global assessment were found with pain score, joint count and patient assessment. In contrast, physician assessment for patients with persistent oligoarticular and rheumatoid factor negative patients showed strong correlation with joint counts, but only moderate correlation with pain scores and patient global assessment. Conversely, for enthesitis patients, physician assessment correlated strongly with pain scores, and moderately with joint count and patient global assessment. Rheumatoid factor positive patients, the smallest group studied, showed moderate correlation for all three measures. Patient global assessment for systemic patients showed strong correlations with pain scores and joint count, similar to data for physician assessment. For polyarticular and enthesitis patients, correlation of patient global assessment with pain scores was strong. Moderate correlations were found between patient global assessment and joint count in oligoarticular and polyarticular patients. Conclusion Data extraction from the EMR is feasible and useful to evaluate JIA patients for indicators of treatment responsiveness. In this pilot study, we found correlates for physician global assessment of arthritis differed, according to disease subtype. Further data extraction and analyses will determine if these findings can be confirmed, and will assess other outcome measures, compare longitudinal responses to treatment, and export extracted data to multi-center databases.

Abstract Background The content and composition of cerebrospinal fluid (CSF) is determined in large part by the choroid plexus (CP) and specifically, a specialized epithelial cell (CPe) layer that responds to, synthesizes, and transports peptide hormones into and out of CSF. Together with ventricular ependymal cells, these CPe relay homeostatic signals throughout the central nervous system (CNS) and regulate CSF hydrodynamics. One new candidate signal is augurin, a newly recognized 14 kDa protein that is encoded by esophageal cancer related gene-4 (Ecrg4), a putative tumor suppressor gene whose presence and function in normal tissues remains unexplored and enigmatic. The aim of this study was to explore whether Ecrg4 and its product augurin, can be implicated in CNS development and the response to CNS injury. Methods Ecrg4 gene expression in CNS and peripheral tissues was studied by in situ hybridization and quantitative RT-PCR. Augurin, the protein encoded by Ecrg4, was detected by immunoblotting, immunohistochemistry and ELISA. The biological consequence of augurin over-expression was studied in a cortical stab model of rat CNS injury by intra-cerebro-ventricular injection of an adenovirus vector containing the Ecrg4 cDNA. The biological consequences of reduced augurin expression were evaluated by characterizing the CNS phenotype caused by Ecrg4 gene knockdown in developing zebrafish embryos. Results Gene expression and immunohistochemical analyses revealed that, the CP is a major source of Ecrg4 in the CNS and that Ecrg4 mRNA is predominantly localized to choroid plexus epithelial (CPe), ventricular and central canal cells of the spinal cord. After a stab injury into the brain however, both augurin staining and Ecrg4 gene expression decreased precipitously. If the loss of augurin was circumvented by over-expressing Ecrg4 in vivo, BrdU incorporation by cells in the subependymal zone decreased. Inversely, gene knockdown of Ecrg4 in developing zebrafish embryos caused increased proliferation of GFAP-positive cells and induced a dose-dependent hydrocephalus-like phenotype that could be rescued by co-injection of antisense morpholinos with Ecrg4 mRNA. Conclusion An unusually elevated expression of the Ecrg4 gene in the CP implies that its product, augurin, plays a role in CP-CSF-CNS function. The results are all consistent with a model whereby an injury-induced decrease in augurin dysinhibits target cells at the ependymal-subependymal interface. We speculate that the ability of CP and ependymal epithelium to alter the progenitor cell response to CNS injury may be mediated, in part by Ecrg4. If so, the canonic control of its promoter by DNA methylation may implicate epigenetic mechanisms in neuroprogenitor fate and function in the CNS.

Abstract Background The late life disability instrument (LLDI) was developed to assess limitations in instrumental and management roles using a small and restricted sample. In this paper we examine the measurement properties of the LLDI using data from the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study. Methods LIFE-P participants, aged 70-89 years, were at elevated risk of disability. The 424 participants were enrolled at the Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University. Physical activity and successful aging health education interventions were compared after 12-months of follow-up. Using factor analysis, we determined whether the LLDI's factor structure was comparable with that reported previously. We further examined how each item related to measured disability using item response theory (IRT). Results The factor structure for the limitation domain within the LLDI in the LIFE-P study did not corroborate previous findings. However, the factor structure using the abbreviated version was supported. Social and personal role factors were identified. IRT analysis revealed that each item in the social role factor provided a similar level of information, whereas the items in the personal role factor tended to provide different levels of information. Conclusions Within the context of community-based clinical intervention research in aged populations, an abbreviated version of the LLDI performed better than the full 16-item version. In addition, the personal subscale would benefit from additional research using IRT. Trial registration The protocol of LIFE-P is consistent with the principles of the Declaration of Helsinki and is registered at http://www.ClinicalTrials.gov (registration # NCT00116194).

Abstract Background Proximal femoral fractures are associated with increased morbidity and mortality. Pre-existing malnutrition and weight loss amongst this patient group is of primary concern, with conventional nutrition support being largely ineffective. The inflammatory response post proximal femoral fracture surgery and the subsequent risk of cachexia may explain the inability of conventional high energy high protein management to produce an anabolic response amongst these patients. Omega-3 fatty acids derived from fish oils have been extensively studied for their anti-inflammatory benefits. Due to their anti-inflammatory properties, the benefit of fish oil combined with individualized nutrition support amongst proximal femoral fracture patients post surgery is an attractive potential therapeutic strategy. The aim of the ATLANTIC trial is to assess the potential benefits of an anti-inflammatory dose of fish oil within the context of a 12 week individualised nutrition program, commencing seven days post proximal femoral fracture surgery. Methods/Design This randomized controlled, double blinded trial, will recruit 150 community dwelling elderly patients aged ≥65 years, within seven days of surgery for proximal femoral fracture. Participants will be randomly allocated to receive either a 12 week individualized nutrition support program complemented with 20 ml/day anti-inflammatory dose fish oil (~3.6 g eicosapentaenoic acid, ~2.4 g docosahexanoic acid; intervention), or, a 12 week individualized nutrition support program complemented with 20 ml/day low dose fish oil (~0.36 g eicosapentaenoic acid, ~0.24 g docosahexanoic acid; control). Discussion The ATLANTIC trial is the first of its kind to provide fish oil combined with individualized nutrition therapy as an intervention to address the inflammatory response experienced post proximal femoral fracture surgery amongst elderly patients. The final outcomes of this trial will assist clinicians in the development of effective and alternative treatment methods post proximal femoral fracture surgery which may ultimately result in a reduction in systemic inflammation, loss of weight and lean muscle and improvements in nutritional status, mobility, independence and quality of life among elderly patients. Trial Registration ACTRN12609000241235

Abstract Background The Freezing of Gait Questionnaire (FOGQ) was developed in response to the difficulties of observing and quantifying freezing of gait (FOG) clinically as well as in laboratory settings. However, as the FOGQ is a clinician-administered patient-reported rating scale it cannot be used in postal surveys. Here we report the development and measurement properties of a self-administered version of the FOGQ (FOGQsa). Methods A clinical sample and a postal survey sample of non-demented people with Parkinson's disease (PD; total n = 225) completed the FOGQsa and questionnaires concerning physical functioning (PF) and fall-related self efficacy (FES). Additional questions (No/Yes) regarded previous falls and whether they were afraid of falling. The clinical sample was also assessed with the Unified PD Rating Scale (UPDRS). Thirty-five participants completed FOGQsa and were also assessed with the original version (FOGQ) in a clinical interview. Results There were no differences (P = 0.12) between FOGQ (median, 10; q1-q3, 2-14) and FOGQsa (median, 8; 2-14) scores. The Spearman (rs) and intra-class correlations between the two were 0.92 and 0.91 (95% CI, 0.82-0.95), respectively. For FOGQsa, corrected item-total correlations ranged between 0.68-0.89. Reliability was 0.93 (95% CI, 0.91-0.94). FOGQsa scores correlated strongest with UPDRS Item 14 (Freezing; rs, 0.76) and with FES (rs, -0.74). The weakest correlation was found with age (rs, 0.14). Fallers scored significantly (p < 0.001) higher on FOGQsa compared to non-fallers, median scores 8 (q1-q3, 4-14) versus 2 (0-7). Those expressing a fear of falling scored higher (p < 0.001) than those who did not, median scores 2 (0-7) versus 6 (2-14). Conclusions The present findings indicate that the FOGQsa is as reliable and valid as the original interview administered FOGQ version. This has important clinical implications when investigating FOG in large scale studies.

Abstract Background Lactobacilli can utilize a variety of carbohydrates which reflects the nutrient availability in their respective environments. A common lactobacilli in the human gastrointestinal tract, Lactobacillus gasseri, was selected for further study. The currently available annotation of the L. gasseri ATCC 33323 genome describes numerous putative genes involved in carbohydrate utilization, yet the specific functions of many of these genes remain unknown. Results An enzyme I (EI) knockout strain revealed that a functional phosphotransferase transporter system (PTS) is required to ferment at least 15 carbohydrates. Analysis of the L. gasseri ATCC 33323 genome identified fifteen complete (containing all of the necessary subunits) PTS transporters. Transcript expression profiles in response to various carbohydrates (glucose, mannose, fructose, sucrose and cellobiose) were analyzed for the fifteen complete PTS transporters in L. gasseri. PTS 20 was induced 27 fold in the presence of sucrose and PTS 15 was induced 139 fold in the presence of cellobiose. No PTS transporter was induced by glucose, fructose or mannose. Insertional inactivation of PTS 15 and PTS 20 significantly impaired growth on cellobiose and sucrose, respectively. As predicted by bioinformatics, insertional inactivation of PTS 21 confirmed its role in mannose utilization. Conclusions The experiments revealed the extensive contribution of PTS transporters to carbohydrate utilization by L. gasseri ATCC 33323 and the general inadequacy of the annotated sugar specificity of lactobacilli PTS transporters.

Abstract Background Tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) are the three components of the once-daily, single tablet regimen (Atripla) for treatment of HIV-1 infection. Previous cell culture studies have demonstrated that the double combination of tenofovir (TFV), the parent drug of TDF, and FTC were additive to synergistic in their anti-HIV activity, which correlated with increased levels of intracellular phosphorylation of both compounds. Results In this study, we demonstrated the combinations of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV synergistically inhibit HIV replication in cell culture and synergistically inhibit HIV-1 reverse transcriptase (RT) catalyzed DNA synthesis in biochemical assays. Several different methods were applied to define synergy including median-effect analysis, MacSynergy®II and quantitative isobologram analysis. We demonstrated that the enhanced formation of dead-end complexes (DEC) by HIV-1 RT and TFV-terminated DNA in the presence of FTC-triphosphate (TP) could contribute to the synergy observed for the combination of TFV+FTC, possibly through reduced terminal NRTI excision. Furthermore, we showed that EFV facilitated efficient formation of stable, DEC-like complexes by TFV- or FTC-monophosphate (MP)-terminated DNA and this can contribute to the synergistic inhibition of HIV-1 RT by TFV-diphosphate (DP)+EFV and FTC-TP+EFV combinations. Conclusion This study demonstrated a clear correlation between the synergistic antiviral activities of TFV+FTC, TFV+EFV, FTC+EFV, and TFV+FTC+EFV combinations and synergistic HIV-1 RT inhibition at the enzymatic level. We propose the molecular mechanisms for the TFV+FTC+EFV synergy to be a combination of increased levels of the active metabolites TFV-DP and FTC-TP and enhanced DEC formation by a chain-terminated DNA and HIV-1 RT in the presence of the second and the third drug in the combination. This study furthers the understanding of the longstanding observations of synergistic anti-HIV-1 effects of many NRTI+NNRTI and certain NRTI+NRTI combinations in cell culture, and provides biochemical evidence that combinations of anti-HIV agents can increase the intracellular drug efficacy, without increasing the extracellular drug concentrations.

Abstract Background Mutations at splice junctions causing exon skipping are uncommon compared to exonic mutations, and two intronic mutations causing an aberrant phenotype have rarely been reported. Despite the high number of functional ABCA1 mutations reported to date, splice variants have been reported infrequently. We screened DNA from a 41 year-old male with low HDL-C (12 mg/dL [0.31 mmol/L]) and a family history of premature coronary heart disease (CHD) using polymerase chain reaction single-strand conformation polymorphism (SSCP) analysis. Methods Family members with low levels of HDL-C (n = 6) were screened by SSCP for mutations in ABCA1. Samples with altered SSCP patterns were sequenced directly using either an ABI 3700 or ABI3730Xl DNA Analyzer. To screen for splicing defects, cDNA was isolated from the proband's RNA and was sequenced as above. A series of minigenes were constructed to determine the contribution of normal and defective alleles. Results Two novel splice variants in ABCA1 were identified. The first mutation was a single base pair change (T->C) in IVS 7, 6 bps downstream from the exon7/intron7 junction. Amplification of cDNA and allelic subcloning identified skipping of Exon 7 that results in the elimination of 59 amino acids from the first extracellular loop of the ABCA1 protein. The second mutation was a single base pair change (G->C) at IVS 31 -1, at the intron/exon junction of exon 32. This mutation causes skipping of exon 32, resulting in 8 novel amino acids followed by a stop codon and a predicted protein size of 1496 AA, compared to normal (2261 AA). Bioinformatic studies predicted an impact on splicing as confirmed by in vitro assays of constitutive splicing. Conclusion In addition to carnitine-acylcarnitine translocase (CACT) deficiency and Hermansky-Pudlak syndrome type 3, this represents only the third reported case in which 2 different splice mutations has resulted in an aberrant clinical phenotype.

Abstract Background tmRNA acts first as a tRNA and then as an mRNA to rescue stalled ribosomes in eubacteria. Two unanswered questions about tmRNA function remain: how does tmRNA, lacking an anticodon, bypass the decoding machinery and enter the ribosome? Secondly, how does the ribosome choose the proper codon to resume translation on tmRNA? According to the -1 triplet hypothesis, the answer to both questions lies in the unique properties of the three nucleotides upstream of the first tmRNA codon. These nucleotides assume an A-form conformation that mimics the codon-anticodon interaction, leading to recognition by the decoding center and choice of the reading frame. The -1 triplet hypothesis is important because it is the most credible model in which direct binding and recognition by the ribosome sets the reading frame on tmRNA. Results Conformational analysis predicts that 18 triplets cannot form the correct structure to function as the -1 triplet of tmRNA. We tested the tmRNA activity of all possible -1 triplet mutants using a genetic assay in Escherichia coli. While many mutants displayed reduced activity, our findings do not match the predictions of this model. Additional mutagenesis identified sequences further upstream that are required for tmRNA function. An immunoblot assay for translation of the tmRNA tag revealed that certain mutations in U85, A86, and the -1 triplet sequence result in improper selection of the first codon and translation in the wrong frame (-1 or +1) in vivo. Conclusion Our findings disprove the -1 triplet hypothesis. The -1 triplet is not required for accommodation of tmRNA into the ribosome, although it plays a minor role in frame selection. Our results strongly disfavor direct ribosomal recognition of the upstream sequence, instead supporting a model in which the binding of a separate ligand to A86 is primarily responsible for frame selection.

Abstract Background Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25–35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers. Methods and Design This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months), ANCOVA or logistic regression will be used with models adjusted according to potential confounders. Discussion The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers. Trial registration Australian Clinical Trials Registry: ACTRN12607000017426.

Abstract Background Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. Results We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. Conclusion MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML.

This paper describes the application of the alternating Kernel mixture (AKM) segmentation algorithm to high resolution MRI subvolumes acquired from a 1.5T scanner (hippocampus, n = 10 and prefrontal cortex, n = 9) and a 3T scanner (hippocampus, n = 10 and occipital lobe, n = 10). Segmentation of the subvolumes into cerebrospinal fluid, gray matter, and white matter tissue is validated by comparison with manual segmentation. When compared with other segmentation methods that use traditional Bayesian segmentation, AKM yields smaller errors (P < .005, exact Wilcoxon signed rank test) demonstrating the robustness and wide applicability of AKM across different structures. By generating multiple mixtures for each tissue compartment, AKM mimics the increased variation of manual segmentation in partial volumes due to the highly folded tissues. AKM's superior performance makes it useful for tissue segmentation of subcortical and cortical structures in large-scale neuroimaging studies. [ABSTRACT FROM AUTHOR]

By analyzing interpoint comparisons, we obtain significant results describing the relationship in 'hippocampus shape space' of clinically depressed, high-risk, and control populations. In particular, our analysis demonstrates that the high-risk population is closer in shape space to the control population than to the clinically depressed population. [ABSTRACT FROM AUTHOR]

Advancements in imaging and molecular techniques enable the collection of subcellular-scale data. Diversity in measured features, resolution, and physical scope of capture across technologies and experimental protocols pose numerous challenges to integrating data with reference coordinate systems and across scales. This resource paper describes a collection of technologies that we have developed for cross-modality 3D mapping for the alignment of transcriptomics at the micron scales of genes and cells to the anatomical tissue scales. Our collection of technologies include (i) an explicit censored data representation for the partial matching problem mapping whole brains to subsampled subvolumes, (ii) image-varifold measure norms for supporting nearly universal crossing of modality, (iii) a multi, scale-space optimization technology for generating resampling grids optimized to represent spatial geometry at fixed complexities, and (iv) mutual-information based functional feature selection. Collectively, these methods afford efficient representations of peta-scale imagery providing the algorithms for mapping from the nano to millimeter scales which we term cross-modality image-varifold LDDMM (xIV-LDDMM)., Competing Interests: Competing Interests. Under a license agreement between AnatomyWorks and the Johns Hopkins University, Dr. Miller and the University are entitled to royalty distributions related to technology described in the study discussed in this. Dr. Miller is a founder of and holds equity in AnatomyWorks. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The remaining authors declare no conflicts of interest.

Background and Purpose: Contrast staining is a common finding after endovascular treatment of acute ischemic stroke. It typically occurs in infarcted tissue and is considered an indicator of irreversible brain damage. Contrast staining in noninfarcted tissue has not been systematically investigated. We sought to assess the incidence, risk factors, and clinical significance of contrast staining in noninfarcted tissue after endovascular treatment., Materials and Methods: We conducted a retrospective review of consecutive patients who underwent endovascular treatment for anterior circulation large-vessel occlusion acute ischemic stroke. Contrast staining, defined as new hyperdensity on CT after endovascular treatment, was categorized as either contrast staining in infarcted tissue if the stained region demonstrated restricted diffusion on follow-up MR imaging or contrast staining in noninfarcted tissue if the stained region demonstrated no restricted diffusion. Baseline differences between patients with and without contrast staining in noninfarcted tissue were compared. Logistic regression was used to identify independent associations for contrast staining in noninfarcted tissue after endovascular treatment., Results: Among 194 patients who underwent endovascular treatment for large-vessel occlusion acute ischemic stroke and met the inclusion criteria, contrast staining in infarcted tissue was noted in 52/194 (26.8%) patients; contrast staining in noninfarcted tissue, in 26 (13.4%) patients. Both contrast staining in infarcted tissue and contrast staining in noninfarcted tissue were noted in 5.6% (11/194). Patients with contrast staining in noninfarcted tissue were found to have a higher likelihood of having an ASPECTS of 8-10, to be associated with contrast staining in infarcted tissue, and to achieve successful reperfusion compared with those without contrast staining in noninfarcted tissue. In contrast staining in noninfarcted tissue regions, the average attenuation was 40 HU, significantly lower than the contrast staining in infarcted tissue regions (53 HU). None of the patients with contrast staining in noninfarcted tissue had clinical worsening during their hospital stay. The median discharge mRS was significantly lower in patients with contrast staining in noninfarcted tissue than in those without (3 versus 4; P  = .018). No independent predictors of contrast staining in noninfarcted tissue were found., Conclusions: Contrast staining can be seen outside the infarcted tissue after endovascular treatment of acute ischemic stroke, likely attributable to the reversible disruption of the BBB in ischemic but not infarcted tissue. While generally benign, understanding its characteristics is important because it may mimic pathologic conditions such as infarcted tissue and cerebral edema., (© 2024 by American Journal of Neuroradiology.)

This paper explicates a solution to building correspondences between molecular-scale transcriptomics and tissue-scale atlases. This problem arises in atlas construction and cross-specimen/technology alignment where specimens per emerging technology remain sparse and conventional image representations cannot efficiently model the high dimensions from subcellular detection of thousands of genes. We address these challenges by representing spatial transcriptomics data as generalized functions encoding position and high-dimensional feature (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling regions as homogeneous random fields with unknown transcriptomic feature distribution. We solve simultaneously for the minimizing geodesic diffeomorphism of coordinates through LDDMM and for these latent feature densities. We map tissue-scale mouse brain atlases to gene-based and cell-based transcriptomics data from MERFISH and BARseq technologies and to histopathology and cross-species atlases to illustrate integration of diverse molecular and cellular datasets into a single coordinate system as a means of comparison and further atlas construction., (© 2024. The Author(s).)

Advances in the development of largely automated microscopy methods such as MERFISH for imaging cellular structures in mouse brains are providing spatial detection of micron resolution gene expression. While there has been tremendous progress made in the field of Computational Anatomy (CA) to perform diffeomorphic mapping technologies at the tissue scales for advanced neuroinformatic studies in common coordinates, integration of molecular- and cellular-scale populations through statistical averaging via common coordinates remains yet unattained. This paper describes the first set of algorithms for calculating geodesics in the space of diffeomorphisms, what we term space-feature-measure LDDMM, extending the family of large deformation diffeomorphic metric mapping (LDDMM) algorithms to accommodate a space-feature action on marked particles which extends consistently to the tissue scales. It leads to the derivation of a cross-modality alignment algorithm of transcriptomic data to common coordinate systems attached to standard atlases. We represent the brain data as geometric measures, termed as space-feature measures supported by a large number of unstructured points, each point representing a small volume in space and carrying a list of densities of features elements of a high-dimensional feature space. The shape of space-feature measure brain spaces is measured by transforming them by diffeomorphisms. The metric between these measures is obtained after embedding these objects in a linear space equipped with the norm, yielding a so-called "chordal metric"., Competing Interests: Declaration of competing interest Michael Miller owns a founder share of Anatomy Works with the arrangement being managed by Johns Hopkins University in accordance with its conflict of interest policies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The amygdala was highlighted as an early site for neurofibrillary tau tangle pathology in Alzheimer's disease in the seminal 1991 article by Braak and Braak. This knowledge has, however, only received traction recently with advances in imaging and image analysis techniques. Here, we provide a cross-disciplinary overview of pathology and neuroimaging studies on the amygdala. These studies provide strong support for an early role of the amygdala in Alzheimer's disease and the utility of imaging biomarkers of the amygdala in detecting early changes and predicting decline in cognitive functions and neuropsychiatric symptoms in early stages. We summarize the animal literature on connectivity of the amygdala, demonstrating that amygdala nuclei that show the earliest and strongest accumulation of neurofibrillary tangle pathology are those that are connected to brain regions that also show early neurofibrillary tangle accumulation. Additionally, we propose an alternative pathway of neurofibrillary tangle spreading within the medial temporal lobe between the amygdala and the anterior hippocampus. The proposed existence of this pathway is strengthened by novel experimental data on human functional connectivity. Finally, we summarize the functional roles of the amygdala, highlighting the correspondence between neurofibrillary tangle accumulation and symptomatic profiles in Alzheimer's disease. In summary, these findings provide a new impetus for studying the amygdala in Alzheimer's disease and a unique perspective to guide further study on neurofibrillary tangle spreading and the occurrence of neuropsychiatric symptoms in Alzheimer's disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Over the past two decades Biomedical Engineering has emerged as a major discipline that bridges societal needs of human health care with the development of novel technologies. Every medical institution is now equipped at varying degrees of sophistication with the ability to monitor human health in both non-invasive and invasive modes. The multiple scales at which human physiology can be interrogated provide a profound perspective on health and disease. We are at the nexus of creating "avatars" (herein defined as an extension of "digital twins") of human patho/physiology to serve as paradigms for interrogation and potential intervention. Motivated by the emergence of these new capabilities, the IEEE Engineering in Medicine and Biology Society, the Departments of Biomedical Engineering at Johns Hopkins University and Bioengineering at University of California at San Diego sponsored an interdisciplinary workshop to define the grand challenges that face biomedical engineering and the mechanisms to address these challenges. The Workshop identified five grand challenges with cross-cutting themes and provided a roadmap for new technologies, identified new training needs, and defined the types of interdisciplinary teams needed for addressing these challenges. The themes presented in this paper include: 1) accumedicine through creation of avatars of cells, tissues, organs and whole human; 2) development of smart and responsive devices for human function augmentation; 3) exocortical technologies to understand brain function and treat neuropathologies; 4) the development of approaches to harness the human immune system for health and wellness; and 5) new strategies to engineer genomes and cells., (© 2023 The Authors.)

Objective: Internal Jugular Vein Stenosis (IJVS) is hypothesized to play a role in the pathogenesis of diverse neurological diseases. We sought to evaluate differences in IJVS assessment between CT and MRI in a retrospective patient cohort., Methods: We included consecutive patients who had both MRI of the brain and CT of the head and neck with contrast from 1 June 2021 to 30 June 2022 within the same admission. The degree of IJVS was categorized into five grades (0-IV)., Results: A total of 35 patients with a total of 70 internal jugular (IJ) veins were included in our analysis. There was fair intermodality agreement in stenosis grades (κ = 0.220, 95% C.I. = [0.029, 0.410]), though categorical stenosis grades were significantly discordant between imaging modalities, with higher grades more frequent in MRI (χ 2 = 27.378, p = 0.002). On CT-based imaging, Grade III or IV stenoses were noted in 17/70 (24.2%) IJs, whereas on MRI-based imaging, Grade III or IV stenoses were found in 40/70 (57.1%) IJs. Among veins with Grade I-IV IJVS, MRI stenosis estimates were significantly higher than CT stenosis estimates (77.0%, 95% C.I. [35.9-55.2%] vs. 45.6%, 95% C.I. [35.9-55.2%], p < 0.001)., Conclusion: MRI with contrast overestimates the degree of IJVS compared to CT with contrast. Consideration of this discrepancy should be considered in diagnosis and treatment planning in patients with potential IJVS-related symptoms.

The international neuroscience community is building the first comprehensive atlases of brain cell types to understand how the brain functions from a higher resolution, and more integrated perspective than ever before. In order to build these atlases, subsets of neurons (e.g. serotonergic neurons, prefrontal cortical neurons etc.) are traced in individual brain samples by placing points along dendrites and axons. Then, the traces are mapped to common coordinate systems by transforming the positions of their points, which neglects how the transformation bends the line segments in between. In this work, we apply the theory of jets to describe how to preserve derivatives of neuron traces up to any order. We provide a framework to compute possible error introduced by standard mapping methods, which involves the Jacobian of the mapping transformation. We show how our first order method improves mapping accuracy in both simulated and real neuron traces under random diffeomorphisms. Our method is freely available in our open-source Python package brainlit., (© 2023. The Author(s).)