[Egg intake and cardiovascular risk factors in adolescents: role of physical activity; the HELENA study].
Cardiovascular diseases (CVDs) represent the main cause of morbi-mortality in western countries. Serum cholesterol levels have been related to cardiovascular disease (CVD). Egg intake has been indirectly related to the risk of developing CVD because of its high cholesterol content. The aim of the present study was to examine the association between egg intake and CVD risk factors in adolescents, assessing the possible influence of physical activity. We studied 380 adolescents enrolled in the HELENA (HEalthy Lifestyle in Europe by Nutrition in Adolescence) study. Food intake was estimated by 2 nonconsecutive 24 h recalls. We measured adiposity indicators, lipid profile, blood glucose and insulin levels, insulin resistance, blood pressure and cardiorespiratory fitness. A CVD risk score was computed as a measure of the overall CVD risk profile. Physical activity was objectively measured by accelerometry. Sexual development was examined. Socioeconomic and smoking statuses were obtained by questionnaire. The association between egg intake and CVD risk factors was examined using a multilevel analysis adjusted for potential confounders. Egg intake was not associated with lipid profile, adiposity, insulin resistance, blood pressure, cardiorespiratory fitness or the integrated CVD risk score. This lack of association was not influenced by physical activity. The findings of the present study suggest that egg intake is not associated with a less favorable lipid or CVD risk profile in adolescents. This lack of association is not influenced by the level of physical activity.


Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial.
Spinal muscular atrophy type 1 is a motor neuron disorder resulting in death or the need for permanent ventilation by age 2 years. We aimed to evaluate the safety and efficacy of onasemnogene abeparvovec (previously known as AVXS-101), a gene therapy delivering the survival motor neuron gene (SMN), in symptomatic patients (identified through clinical examination) with infantile-onset spinal muscular atrophy. STR1VE was an open-label, single-arm, single-dose, phase 3 trial done at 12 hospitals and universities in the USA. Eligible patients had to be younger than 6 months and have spinal muscular atrophy with biallelic SMN1 mutations (deletion or point mutations) and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes per kg) for 30-60 min. During the outpatient follow-up, patients were assessed once per week, beginning at day 7 post-infusion for 4 weeks and then once per month until the end of the study (age 18 months or early termination). Coprimary efficacy outcomes were independent sitting for 30 s or longer (Bayley-III item 26) at the 18 month of age study visit and survival (absence of death or permanent ventilation) at age 14 months. Safety was assessed through evaluation of adverse events, concomitant medication usage, physical examinations, vital sign assessments, cardiac assessments, and laboratory evaluation. Primary efficacy endpoints for the intention-to-treat population were compared with untreated infants aged 6 months or younger (n=23) with spinal muscular atrophy type 1 (biallelic deletion of SMN1 and two copies of SMN2) from the Pediatric Neuromuscular Clinical Research (PNCR) dataset. This trial is registered with ClinicalTrials.gov, NCT03306277 (completed). From Oct 24, 2017, to Nov 12, 2019, 22 patients with spinal muscular atrophy type 1 were eligible and received onasemnogene abeparvovec. 13 (59%, 97·5% CI 36-100) of 22 patients achieved functional independent sitting for 30 s or longer at the 18 month of age study visit (vs 0 of 23 patients in the untreated PNCR cohort; p<0·0001). 20 patients (91%, 79-100]) survived free from permanent ventilation at age 14 months (vs 6 [26%], 8-44; p<0·0001 in the untreated PNCR cohort). All patients who received onasemnogene abeparvovec had at least one adverse event (most common was pyrexia). The most frequently reported serious adverse events were bronchiolitis, pneumonia, respiratory distress, and respiratory syncytial virus bronchiolitis. Three serious adverse events were related or possibly related to the treatment (two patients had elevated hepatic aminotransferases, and one had hydrocephalus). Results from this multicentre trial build on findings from the phase 1 START study by showing safety and efficacy of commercial grade onasemnogene abeparvovec. Onasemnogene abeparvovec showed statistical superiority and clinically meaningful responses when compared with observations from the PNCR natural history cohort. The favourable benefit-risk profile shown in this study supports the use of onasemnogene abeparvovec for treatment of symptomatic patients with genetic or clinical characteristics predictive of infantile-onset spinal muscular atrophy type 1. Novartis Gene Therapies.


Trifascicular block progressing to complete AV block on exercise: a rare presentation demonstrating the usefulness of exercise testing.
A 41-year-old man presented with dyspnoea and giddiness on exertion for the last 1 month. A resting ECG during showed trifascicular block with complete right bundle branch block, left anterior fascicular block and a prolonged PR interval of >0.24 s. His echocardiography showed no evidence of wall motion abnormality. He was subjected to a treadmill test for exercise-induced ischaemia, which showed complete atrioventricular (AV) block during first stage of Bruce protocol. His symptoms of dyspnoea and giddiness were also reproduced. The test was terminated and ECG returned to trifascicular block, similar to that at his baseline ECG during recovery. Coronary angiogram (CAG) was performed to rule out any ischaemic cause for this exercise-induced AV block, which was normal. In view of his reproducible symptoms and demonstration of complete AV block on exercise, a dual-chamber pacemaker (DDD) was implanted. His symptoms disappeared and he remained asymptomatic on follow-up.


Preparation of single cells from tumors for single-cell RNA sequencing.
Intratumoral heterogeneity of cancer cells and tumor-infiltrating immune cells is increasingly being viewed as a key factor driving tumor progression and response to therapy. Over the past several years, technological advances have created powerful tools to analyze the tumor microenvironment on a single-cell level, including mass cytometry and single-cell RNA sequencing, which is particularly pertinent to tumor immunology and cancer immunotherapy. The integrity and reliability of the data generated from these single-cell technologies, however, are highly influenced by the process and quality of sample preparation, which, if carried out inappropriately, has a potential to produce misleading results. In this chapter, we describe a protocol for the generation of single cell suspensions from human tumor samples that has been optimized for single-cell RNA sequencing. This protocol can be easily adapted for other single cell applications such as mass and flow cytometry. Throughout the entire workflow, we aim to maximize viability and minimize factors contributing to cellular stress that could affect downstream analyses.


Whole Genomic Analysis of an Unusual Human G6P[14] Rotavirus Strain Isolated from a Child with Diarrhea in Thailand: Evidence for Bovine-To-Human Interspecies Transmission and Reassortment Events.
An unusual rotavirus strain, SKT-27, with the G6P[14] genotypes (RVA/Human-wt/THA/SKT-27/2012/G6P[14]), was identified in a stool specimen from a hospitalized child aged eight months with severe diarrhea. In this study, we sequenced and characterized the complete genome of strain SKT-27. On whole genomic analysis, strain SKT-27 was found to have a unique genotype constellation: G6-P[14]-I2-R2-C2-M2-A3-N2-T6-E2-H3. The non-G/P genotype constellation of this strain (I2-R2-C2-M2-A3-N2-T6-E2-H3) is commonly shared with rotavirus strains from artiodactyls such as cattle. Phylogenetic analysis indicated that nine of the 11 genes of strain SKT-27 (VP7, VP4, VP6, VP2-3, NSP1, NSP3-5) appeared to be of artiodactyl (likely bovine) origin, while the remaining VP1 and NSP2 genes were assumed to be of human origin. Thus, strain SKT-27 was found to have a bovine rotavirus genetic backbone, and thus is likely to be of bovine origin. Furthermore, strain SKT-27 appeared to be derived through interspecies transmission and reassortment events involving bovine and human rotavirus strains. Of note is that the VP7 gene of strain SKT-27 was located in G6 lineage-5 together with those of bovine rotavirus strains, away from the clusters comprising other G6P[14] strains in G6 lineages-2/6, suggesting the occurrence of independent bovine-to-human interspecies transmission events. To our knowledge, this is the first report on full genome-based characterization of human G6P[14] strains that have emerged in Southeast Asia. Our observations will provide important insights into the origin of G6P[14] strains, and into dynamic interactions between human and bovine rotavirus strains.


Polygenic inheritance, GWAS, polygenic risk scores, and the search for functional variants.
The reconciliation between Mendelian inheritance of discrete traits and the genetically based correlation between relatives for quantitative traits was Fisher's infinitesimal model of a large number of genetic variants, each with very small effects, whose causal effects could not be individually identified. The development of genome-wide genetic association studies (GWAS) raised the hope that it would be possible to identify single polymorphic variants with identifiable functional effects on complex traits. It soon became clear that, with larger and larger GWAS on more and more complex traits, most of the significant associations had such small effects, that identifying their individual functional effects was essentially hopeless. Polygenic risk scores that provide an overall estimate of the genetic propensity to a trait at the individual level have been developed using GWAS data. These provide useful identification of groups of individuals with substantially increased risks, which can lead to recommendations of medical treatments or behavioral modifications to reduce risks. However, each such claim will require extensive investigation to justify its practical application. The challenge now is to use limited genetic association studies to find individually identifiable variants of significant functional effect that can help to understand the molecular basis of complex diseases and traits, and so lead to improved disease prevention and treatment. This can best be achieved by 1) the study of rare variants, often chosen by careful candidate assessment, and 2) the careful choice of phenotypes, often extremes of a quantitative variable, or traits with relatively high heritability.


Presentation of a self-peptide for in vivo tolerance induction of CD4+ T cells is governed by a processing factor that maps to the class II region of the major histocompatibility complex locus.
Self-proteins are regularly processed for presentation to autoreactive T cells in association with both class I and class II major histocompatibility complex (MHC) molecules. The presentation of self-peptides plays a crucial role in the acquisition of T cell repertoire during thymic selection. We previously reported that the self-MHC class I peptide Ld 61-80 was immunogenic in syngeneic B10.A mice (H-2a). We showed that despite its high affinity for self-MHC class II molecules, Ld 61-80 peptide failed to induce elimination of autoreactive CD4+ T cells, presumably due to incomplete processing and presentation in the B10.A's developing thymus (cryptic-self peptide). In this report, we showed that the cryptic phenotype was not an intrinsic property of the self-peptide Ld 61-80 since it was found to be naturally presented and subsequently tolerogenic in BALB/c mice (H-2d) (dominant self-peptide). In addition, the self-peptide Ld 61-80 was found to be immunogenic in different H-2a mice while it was invariably tolerogenic in H-2d mice regardless of their background genes. We observed that Ld 61-80 bound equally well to H-2d and H-2k MHC class II molecules. Also, no correlation was found between the quantity of self-Ld protein and the tolerogenicity of Ld 61-80. Surprisingly, Ld 61-80 was not naturally presented in (H-2d x H-2a) F1 mice, indicating that the H-2a MHC locus contained a gene that impaired the presentation of the self-peptide. Analyses of T cell responses to the self-peptide in several H-2 recombinant mice revealed that the presentation of Ld 61-80 was controlled by genes that mapped to a 170-kb portion of the MHC class II region. This study shows that (a) endogenously processed self-peptides presented by MHC class II molecules are involved in shaping the CD4+ T cell repertoire in the thymus; (b) The selection of self-peptides for presentation by MHC class II molecules to nascent autoreactive T cells is influenced by nonstructural MHC genes that map to a 170-kb portion of the MHC class II region; and (c) the MHC locus of H-2a mice encodes factors that prevent or abrogate the presentation by MHC class II molecules of the self-peptide Ld 61-80. These findings may have important implications for understanding the molecular mechanisms involved in T cell repertoire acquisition and self-tolerance induction.


Physical activity in persons with late effects of polio: a descriptive study.
To promote a healthy and active lifestyle there is a need to increase our knowledge of the level of physical activity (PA) among people with late effects of polio. To examine PA in people with late effects of polio and to assess the relationship between PA, life satisfaction and various sociodemographic factors. PA was assessed in 81 persons with late effects of polio using the Physical Activity and Disability Survey (PADS) and by a pedometer. Life satisfaction was assessed with the Life Satisfaction Questionnaire (LiSat-11). The amount of PA varied considerably but on average the participants were physically active almost 3 h per day, mostly in household activities. The mean value of the pedometer counts was 6212 steps per day (SD = 3208). Sixty-nine percent of the participants rated themselves as satisfied with life as a whole. The sum of PADS was positively and significantly related to the number of steps (r = 0.39, p < 0.001), increasing age (r = 0.26, p < 0.05) and to the level of global satisfaction with life (rho = 0.23, p < 0.05). The number of steps was also positively and significantly associated with level of global satisfaction with life (rho = 0.37, p < 0.001). Despite a progressive physical disability, people with late effects of polio are physically active, but much of the activities are performed as part of their household activities and not as traditional exercise. The relationship between PA, life satisfaction and age further supports the general contention that an active lifestyle is an important factor for perceived well-being among older people.


Long-term Results After Repair of Isolated Meniscal Tears Among Patients Aged 18 Years and Younger: An 18-Year Follow-up Study.
Meniscal repair is desirable over resection to prevent postmeniscectomy arthritis, especially among young and active patients. However, long-term data are currently lacking following isolated meniscal repair, particularly in the pediatric population. To report long-term follow-up of isolated meniscal tears treated by meniscal repair in a pediatric and adolescent population and to compare those results with previous midterm follow-up data reported. The authors hypothesized that these patients would have satisfactory function and reoperation rates at long-term follow-up. Case series; Level of evidence, 4. Forty-four patients aged ≤18 years undergoing repair of an isolated meniscal tear (without concomitant anterior cruciate ligament injury) between 1990 and 2005 were included. At the time of final follow-up, recurrent tear, reoperations, and International Knee Documentation Committee (IKDC) and Tegner scores were determined. With logistic regression, the overall failure among tear types was calculated. Wilcoxon rank sum analysis were performed to calculate the differences in clinical outcome for different time points, and Spearman coefficients were calculated for Tegner and IKDC with different variables. At a mean follow-up of 17.6 years (range, 13.1-25.9 years), 32 patients with 33 isolated meniscal repairs (29 male, 3 female) with a mean age of 16.1 years (range, 9.9-18.7 years) at surgery were included in this study. At early follow-up, the overall failure rate was 14 of 33 (42%); complex tears (80%) and bucket-handle tears (47%) had higher overall failure rates when compared with simple tears (18.2%), although only complex tears had a significantly higher failure rate. However, no further failures occurred since midterm follow-up with any tear type. At final follow-up, the mean IKDC score was 92.3, which was significantly increased when compared with preoperative (65.3, P < .0001) and midterm (90.2, P = .01) scores. The mean Tegner score (6.5) was significantly lower than both preoperative (8.3, P < .0001) and midterm (8.4, P < .0001) scores. There was no difference in Tegner or IKDC score for patients with successful versus failed repair. In conclusion, while there was a high early failure rate, this study demonstrated overall good to excellent long-term clinical outcomes after isolated meniscal repair in an adolescent population, even for those requiring reoperation. Early failure and reoperation rates were variable, depending on tear type, with complex multiplanar tears having more failures at short-term follow-up. However, at long-term follow-up, IKDC and Tegner scores were not significantly different for those with complex tears as compared with other tear types.


Rituximab therapy leads to reduced imprints of receptor revision in immunoglobulin κ and λ light chains.
Transient B cell depletion by rituximab (RTX) has become a specific treatment of rheumatoid arthritis (RA). Although phenotypic repopulation kinetics of B cell subsets are well documented, precise molecular analyses of the reconstituting immunoglobulin (Ig) genes encoding the B cell receptor in RA are sparse. A total of 708 individual CD19+CD27+ (memory) and CD19+CD27- (naive) B cells from 2 patients with RA were analyzed at baseline and 7 months after RTX at B cell repopulation. Ig light chain variable kappa (Vκ) and lambda (Vλ) light chain gene rearrangements were amplified, sequenced, and analyzed with a focus on receptor revision. The naive as well as the memory repertoire repopulated polyclonally with diverse use of variable light chain gene families and minigenes. During the reconstitution phase, B cells used significantly fewer Jκ distal Vκ genes (p = 0.0006), with a higher frequency of somatic hypermutation of rearrangements employing Jκ5 compared to baseline in memory B cells. The use of Vλ rearrangements in regenerating B cells was also biased toward use of Vλ genes of the proximal cassette. In general, reemerging CD27+ Ig light chain genes were substantially more highly mutated than before RTX therapy (p < 0.0001, baseline vs during reconstitution). Our data indicate that RTX therapy leads to generation of distinct Vκ/Jκ and Vλ/Jλ gene repertoires consistent with replenishment of antigen-experienced B cells by germinal centers. At baseline, the imprints of receptor revision appeared to be more striking, which indicates that receptor revision is active in patients with RA and can be reduced by RTX.


Transcriptional profiling of tissue plasticity: role of shifts in gene expression and technical limitations.
Reprogramming of gene expression has been recognized as a main instructive modality for the adjustments of tissues to various kinds of stress. The recent application of gene expression profiling has provided a powerful tool to elucidate the molecular pathways underlying such tissue remodeling. However, the biological interpretations of expression profiling results critically depend on normalization of transcript signals to mRNA standards before statistical evaluation. A hypothesis is proposed whereby the "fluctuating nature" of gene expression represents an inherent limitation of the test system used to quantify RNA levels. Misinterpretation of gene expression data occurs when RNA quantities are normalized to a subset of mRNAs that are subject to strong regulation. The contention of contradictory biological outcomes using different RNA-normalization schemes is demonstrated in two models of skeletal muscle plasticity with data from custom-designed microarrays and biochemical and ultrastructural evidence for correspondingly altered RNA content and nucleolar activity. The prevalence of these biological constraints is underlined by a literature survey in different models of tissue plasticity with emphasis on the unique malleability of skeletal muscle. Finally, recommendations on the optimal experimental layout are given to control biological and technical variability in microarray and RT-PCR studies. It is proposed to approach normalization of transcript signals by measuring total RNA and DNA content per sample weight and by correcting for concurrently estimated endogenous standards such as major ribosomal RNAs and spiked RNA and DNA species. This allows for later conversion to diverse tissue-relevant references and should improve the physiological interpretations of phenotypic plasticity.


The impact of Fisher's reproductive compensation on raising equilibrium frequencies of semidominant, nonlethal mutations under mutation/selection balance.
Fisher's reproductive compensation (fRC) occurs when a species' demography means the death of an individual results in increased survival probability of his/her relatives, usually assumed to be full sibs. This likely occurs in many species, including humans. Several important recessive human genetic diseases cause early foetal/infant death allowing fRC to act on these mutations. The impact of fRC on these genetic conditions has been previously calculated and shown to be substantial as quantified by ω, the fold increase in equilibrium frequencies of the mutation under fRC compared with its absence, i.e. ω = 1.22 and ω = 1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much larger class of semidominant, nonlethal mutations is unknown. This is calculated here as ω = 2 - h*s for autosomal loci and ω up to 2 for sex-linked loci where h is dominance (varied between 0.05 and 0.95) and s is selection coefficient (varied between 0.05 and 0.9). These results show that the actions of fRC can almost double the equilibrium frequency of deleterious mutations with low values of h and/or s (noting that "low" is s∼0.05 to 0.1). It is noted that fRC may act differentially across the genome with genes expressed early in life being fully exposed to fRC while those expressed later in life may be unaffected; this could lead to systematic differences in deleterious allele frequency across the genome.


Delay discounting, locus of control, and cognitive impulsiveness independently predict tobacco dependence treatment outcomes in a highly dependent, lower socioeconomic group of smokers.
Tobacco use disproportionately affects lower socioeconomic status (SES) groups. Current explanations as to why lower SES groups respond less robustly to tobacco control efforts and tobacco dependence treatment do not fully account for this disparity. The identification of factors that predict relapse in this population might help to clarify these differences. Good candidates for novel prognostic factors include the constellation of behaviors associated with executive function including self-control/impulsiveness, the propensity to delay reward, and consideration and planning of future events. This study examined the ability of several measures of executive function and other key clinical, psychological, and cognitive factors to predict abstinence for highly dependent lower SES participants enrolled in intensive cognitive-behavioral treatment for tobacco dependence. Consistent with predictions, increased discounting and impulsiveness, an external locus of control as well as greater levels of nicotine dependence, stress, and smoking for negative affect reduction predicted relapse. These findings suggest that these novel factors are clinically relevant in predicting treatment outcomes and suggest new targets for therapeutic assessment and treatment approaches.


Microbial ecological processes in MBBR biofilms for biological phosphorus removal from wastewater.
Phosphorus is both a major environmental pollutant and a limiting resource. Although enhanced biological phosphorus removal (EBPR) is used worldwide for phosphorus removal, the standard activated sludge-based EBPR process shows limitations with stability and efficiency. Recently, a new EBPR moving bed biofilm reactor (MBBR) process has been developed at HIAS (Hamar, Norway), enabling a phosphorus removal stability above 90% during a whole year cycle. To increase the knowledge of the HIAS (MBBR) process the aim of the current work was to characterize the MBBR microbiota and operational performance weekly for the operational year. Surprisingly, we found a major succession of the microbiota, with a five-fold increase in phosphorus accumulating organisms (PAOs), and major shifts in eukaryote composition, despite a stable phosphorus removal. Temperature was the only factor that significantly affected both phosphorus removal and the microbiota. There was a lower phosphor removal during the winter, coinciding with a higher microbiota alpha diversity, and a lower beta diversity. This differs from what is observed for activated sludge based EBPR. Taken together, the knowledge gained from the current microbiota study supports the efficiency and stability of MBBR-based systems, and that knowledge from activated sludge-based EBPR approaches cannot be translated to MBBR systems.


Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.
The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.


Automated detection of poor-quality data: case studies in healthcare.
The detection and removal of poor-quality data in a training set is crucial to achieve high-performing AI models. In healthcare, data can be inherently poor-quality due to uncertainty or subjectivity, but as is often the case, the requirement for data privacy restricts AI practitioners from accessing raw training data, meaning manual visual verification of private patient data is not possible. Here we describe a novel method for automated identification of poor-quality data, called Untrainable Data Cleansing. This method is shown to have numerous benefits including protection of private patient data; improvement in AI generalizability; reduction in time, cost, and data needed for training; all while offering a truer reporting of AI performance itself. Additionally, results show that Untrainable Data Cleansing could be useful as a triage tool to identify difficult clinical cases that may warrant in-depth evaluation or additional testing to support a diagnosis.


Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study.
Alcoholic hepatitis (AH) develops in only a small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls were enrolled and followed up to 12 months. At baseline, HDC and healthy controls had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays. However, compared to HDC, AH patients had higher baseline levels of 11 cytokines/chemokines (tumor necrosis factor alpha, interleukin 6 [IL-6], IL-8, interferon gamma-induced protein 10, IL-4, IL-9, IL-10, fibroblast growth factor 2, IL-7, IL-15, and transforming growth factor alpha) but lower levels of the anti-inflammatory macrophage-derived chemokine. AH patients also had more activated yet dysfunctional immune cells as monocytes, T cells, and B cells expressed higher levels of cluster of differentiation 38 (CD38) and CD69 but low levels of human leukocyte antigen DR, CD80, and CD86 at baseline. In addition, CD4 T cells produced less interferon-gamma in response to T-cell stimulation. Up-regulated IL-6, IL-8, CD38, and CD69 and down-regulated macrophage-derived chemokine, human leukocyte antigen DR, CD86, and CD80 correlated positively and negatively, respectively, with disease severity. Longitudinal analysis indicated that levels of IL-6, IL-8, CD38, and CD69 were reduced, whereas levels of macrophage-derived chemokine, human leukocyte antigen DR, CD80, and CD86 were increased in abstinent AH patients. All of the cellular immune abnormalities were reversed by day 360 in abstinent AH patients; however, plasma levels of tumor necrosis factor alpha, IL-8, IL-10, fibroblast growth factor 2, and IL-7 remained higher. AH patients were in a highly immune-dysregulated state, whereas HDC showed little evidence of immune activation; alcohol abstinence reversed most, but not all, of the immunological abnormalities. (Hepatology 2017;66:575-590).


Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11.
Spo11, a protein first identified in yeast, is thought to generate the chromosome breaks that initiate meiotic recombination. We now report that disruption of mouse Spo11 leads to severe gonadal abnormalities from defective meiosis. Spermatocytes suffer apoptotic death during early prophase; oocytes reach the diplotene/dictyate stage in nearly normal numbers, but most die soon after birth. Consistent with a conserved function in initiating meiotic recombination, Dmc1/Rad51 focus formation is abolished. Spo11(-/-) meiocytes also display homologous chromosome synapsis defects, similar to fungi but distinct from flies and nematodes. We propose that recombination initiation precedes and is required for normal synapsis in mammals. Our results also support the view that mammalian checkpoint responses to meiotic recombination and/or synapsis defects are sexually dimorphic.


Transport and storage of vitamin A.
The requirement of vitamin A (retinoids) for vision has been recognized for decades. In addition, vitamin A is involved in fetal development and in the regulation of proliferation and differentiation of cells throughout life. This fat-soluble organic compound cannot be synthesized endogenously by humans and thus is an essential nutrient; a well-regulated transport and storage system provides tissues with the correct amounts of retinoids in spite of normal fluctuations in daily vitamin A intake. An overview is presented here of current knowledge and hypotheses about the absorption, transport, storage, and metabolism of vitamin A. Some information is also presented about a group of ligand-dependent transcription factors, the retinoic acid receptors, that apparently mediate many of the extravisual effects of retinoids.


Community-based coalitions' capacity for sustainable action: the role of relationships.
Given both the importance and difficulty of promoting community-based public health coalitions, their capacity for sustainable action merits systematic examination. The current study addresses this need, focusing specifically on the relational dimension of capacity, that is, how relationships both among members and with external actors affect coalition-level activity. The context is a multimethod comparative case study of two rural cancer control coalitions. The authors began by using quantitative and qualitative data to characterize relational capacity in each coalition and then assessed the association between coalition-level relational capacity and level of subsequent interventions. The more active coalition had a more inclusive relational structure than did its less active counterpart but also placed less emphasis on personal friendships. The authors conclude that coalitions' relational structures are measurable and that this dimension of capacity may affect sustainable capacity for health promotion.


High-resolution analysis of multi-copy variant surface glycoprotein gene expression sites in African trypanosomes.
African trypanosomes cause lethal diseases in humans and animals and escape host immune attack by switching the expression of Variant Surface Glycoprotein (VSG) genes. The expressed VSGs are located at the ends of telomeric, polycistronic transcription units known as VSG expression sites (VSG-ESs). Each cell has many VSG-ESs but only one is transcribed in bloodstream-form parasites and all of them are inactive upon transmission to the insect vector mid-gut; a subset of monocistronic metacyclic VSG-ESs are then activated in the insect salivary gland. Deep-sequence analyses have been informative but assigning sequences to individual VSG-ESs has been challenging because they each contain closely related expression-site associated genes, or ESAGs, thought to contribute to virulence. We utilised ART, an in silico short read simulator to demonstrate the feasibility of accurately aligning reads to VSG-ESs. Then, using high-resolution transcriptomes from isogenic bloodstream and insect-stage Lister 427 Trypanosoma brucei, we uncover increased abundance in the insect mid-gut stage of mRNAs from metacyclic VSG-ESs and of mRNAs from the unusual ESAG, ESAG10. Further, we show that the silencing associated with allelic exclusion involves repression focussed at the ends of the VSG-ESs. We also use the approach to report relative fitness costs following ESAG RNAi from a genome-scale screen. By assigning sequences to individual VSG-ESs we provide new insights into VSG-ES transcription control, allelic exclusion and impacts on fitness. Thus, deeper insights into the expression and function of regulated multi-gene families are more accessible than previously anticipated.


Axis I and Axis II diagnostic parameters of homicide.
A series of 100 murderers was examined to discern overall patterns of psychopathology. In addition, demographic and other discriminating factors were used to test the hypothesis that murderers do not constitute a homogenous population and that subgroups will differ diagnostically. DSM-III diagnostic criteria were used to make each diagnosis. The sample was found to be representative of the universe from which it was drawn at least as could be determined by available comparative criteria. Four Axis I (psychoses, substance abuse, dysthymia, no Axis I) and three Axis II (antisocial, borderline, no Axis II) diagnostic categories accounted for more than 80 percent of the study population. The murderers were found to be a heterogenous population, and subgroups based on a combination of assailant's crime pattern, sex, prior criminal history, and relationship to victim manifested different prevailing diagnostic patterns.


A swimming mammaliaform from the Middle Jurassic and ecomorphological diversification of early mammals.
A docodontan mammaliaform from the Middle Jurassic of China possesses swimming and burrowing skeletal adaptations and some dental features for aquatic feeding. It is the most primitive taxon in the mammalian lineage known to have fur and has a broad, flattened, partly scaly tail analogous to that of modern beavers. We infer that docodontans were semiaquatic, convergent to the modern platypus and many Cenozoic placentals. This fossil demonstrates that some mammaliaforms, or proximal relatives to modern mammals, developed diverse locomotory and feeding adaptations and were ecomorphologically different from the majority of generalized small terrestrial Mesozoic mammalian insectivores.


Jaundice post laparoscopic cholecystectomy.
In just over 20 years, laparoscopic cholecystectomy has emerged as the standard therapy for cholelithiasis and is now being performed with increased safety. However an uncommon complication of this technique has been jaundice even in patients without iatrogenic bile duct injury. We report on two cases where this complication occurred and review the literature on this topic.


Patterns of coordinated multi-joint movement.
In multi-joint reaching movements, the motor system may choose any one of an infinite set of possible joint rotations to move the hand between given start and target positions. In order to find out whether reaching movements are represented in Cartesian hand coordinates or in joint coordinates, it is necessary to measure whether hand paths or joint paths have lower variability. We have measured hand paths and rotations of shoulder, elbow and wrist joints simultaneously in five subjects reaching in four orientations in the horizontal plane. As in earlier studies, we found a preference for nearly straight hand paths, despite different patterns of joint rotation for different orientations of movement. However, movements in three of four orientations showed a single principal joint, which rotated essentially without reversals. This may reflect optimisation in the motor system, preferring the simplest pattern of joint control for a desired hand path. We used generalised Procrustes analysis to quantify the variability in shape of repeated paths in hand space and joint space. Results showed that hand paths were less variable than the joint angles used to realise them, due to the kinematic redundancy of the limb, suggesting that hand paths, rather than joint angles, are directly represented by the motor system. Nevertheless, movements with straighter hand paths, on average, and those requiring coordinated activity at both shoulder and elbow joints also showed more variability in the shape of the hand path. Other orientations such as movement across the body use primarily a single joint and are less variable at the cost of a slightly curved path. These results suggest that coordinating multiple joints to produce a straight hand path has a definite computational cost. The motor system may perform a trade-off between the benefits of planning reaching movements as straight hand paths and the computational simplicity of executing them using patterns of joint rotation which simplify multi-joint coordination.


Antibiotic Use in Cold and Flu Season and Prescribing Quality: A Retrospective Cohort Study.
Excessive antibiotic use in cold and flu season is costly and contributes to antibiotic resistance. The study objective was to develop an index of excessive antibiotic use in cold and flu season and determine its correlation with other indicators of prescribing quality. We included Medicare beneficiaries in the 40% random sample denominator file continuously enrolled in fee-for-service benefits for 2010 or 2011 (7,961,201 person-years) and extracted data on prescription fills for oral antibiotics that treat respiratory pathogens. We collapsed the data to the state level so they could be merged with monthly flu activity data from the Centers for Disease Control and Prevention. Linear regression, adjusted for state-specific mean antibiotic use and demographic characteristics, was used to estimate how antibiotic prescribing responded to state-specific flu activity. Flu-activity associated antibiotic use varied substantially across states-lowest in Vermont and Connecticut, highest in Mississippi and Florida. There was a robust positive correlation between flu-activity associated prescribing and use of medications that often cause adverse events in the elderly (0.755; P<0.001), whereas there was a strong negative correlation with beta-blocker use after a myocardial infarction (-0.413; P=0.003). Adjusted flu-activity associated antibiotic use was positively correlated with prescribing high-risk medications to the elderly and negatively correlated with beta-blocker use after myocardial infarction. These findings suggest that excessive antibiotic use reflects low-quality prescribing. They imply that practice and policy solutions should go beyond narrow, antibiotic specific, approaches to encourage evidence-based prescribing for the elderly Medicare population.


The skin immune response of rainbow trout, Oncorhynchus mykiss (Walbaum), associated with puffy skin disease (PSD).
Puffy skin disease (PSD) is an emerging skin condition which affects rainbow trout, Oncorhynchus mykiss (Walbaum). The transmission pattern of PSD suggests an infectious aetiology, however, the actual causative infectious agent(s) remain(s) unknown. In the present study, the rainbow trout epidermal immune response to PSD was characterised. Skin samples from infected fish were analysed and classified as mild, moderate or severe PSD by gross pathology and histological assessment. The level of expression of 26 immune-associated genes including cytokines, immunoglobulins and cell markers were examined by TaqMan qPCR assays. A significant up-regulation of the gene expression of C3, lysozyme, IL-1β and T-bet and down-regulation of TGFβ and TLR3 was observed in PSD fish compared to control fish. MHCI gene expression was up-regulated only in severe PSD lesions. Histological examinations of the epidermis showed a significant increase in the number of eosinophil cells and dendritic melanocytes in PSD fish. In severe lesions, mild diffuse lymphocyte infiltration was observed. IgT and CD8 positive cells were detected locally in the skin of PSD fish by in situ hybridisation (ISH), however, the gene expression of those genes was not different from control fish. Total IgM in serum of diseased animals was not different from control fish, measured by a sandwich ELISA, nor was significant up regulation of IgM gene expression in PSD lesions observed. Taken together, these results show activation of the complement pathway, up-regulation of a Th17 type response and eosinophilia during PSD. This is typical of a response to extracellular pathogens (i.e. bacteria and parasites) and allergens, commonly associated with acute dermatitis.


"5 mins of uncomfyness is better than dealing with cancer 4 a lifetime": an exploratory qualitative analysis of cervical and breast cancer screening dialogue on Twitter.
Twitter.com is a "micro-blogging" website. Although Twitter use is growing rapidly, little is known about health behavior discussions on this site, even though a majority of messages are publicly available. We retrieved publicly available Twitter messages during a 5-week period in early 2012, searching separately for the terms "Pap smear" and "mammogram." We used content analysis to code each 140-character message, generating a separate coding framework for each cancer screening term and calculating the frequencies of comments. Using the brief account description, we also coded the author as individual, organization, or news media outlet. There were 203 Pap smear and 271 mammogram messages coded, over three fourths of which were from individual accounts. Overall, 22 % of Pap smear messages and 25 % of mammogram messages discussed personal experiences, including attending appointments, negative sentiment about the procedure, and results. Other messages from both individuals and organizations (8 % Pap smear, 18 % mammogram) promoted screening. About one quarter of the messages expressed personal experiences with cancer screening. This demonstrates that Twitter can be a rich source of information and could be used to design new health-related interventions.


Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome.
(1)H NMR spectroscopy of aqueous fecal extracts has been used to investigate differences in metabolic activity of gut microbiota in patients with ulcerative colitis (UC) (n = 13), irritable bowel syndrome (IBS) (n = 10), and healthy controls (C) (n = 22). Up to four samples per individual were collected over 2 years giving a total of 124 samples. Multivariate discriminant analysis, based on NMR data from all three groups, was able to predict UC and C group membership with good sensitivity and specificity; classification of IBS samples was less successful and could not be used for diagnosis. Trends were detected toward increased taurine and cadaverine levels in UC with increased bile acid and decreased branched chain fatty acids in IBS relative to controls; changes in short chain fatty acids and amino acids were not significant. Previous PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis of the same fecal material had shown alterations of the gut microbiota when comparing UC and IBS groups with controls. Hierarchical cluster analysis showed that DGGE profiles from the same individual were stable over time, but NMR spectra were more variable; canonical correlation analysis of NMR and DGGE data partly separated the three groups and revealed a correlation between the gut microbiota profile and metabolite composition.


Stem cells and the skin.
Stem cells live long lives, renew themselves, and differentiate into more mature, less potent, specialized cells, such as epidermal keratinocytes and dermal fibroblasts. Stem cells can be embryonic, if derived from an embryo, or adult/somatic if derived from postembryonic tissue. By producing new skin cells, stem cell division and differentiation can potentially rejuvenate skin and restore hair. To reproduce, stem cells can undergo symmetric nondifferentiative or differentiative divisions, or asymmetric differentiative divisions. Asymmetric divisions reproduce the stem cell and provide a more differentiated, but less potent transient amplifying cell. Divisions and differentiation of transient amplifying cells regenerate tissues by producing cells of a specific lineage, for example, keratinocytes. Epidermal stem cells lie in niches in the interfollicular epidermis, sebaceous gland, and in the bulge regions of hair follicles. These epidermal stem cells renew the epidermis, the sebaceous glands, and hair follicles after mature cells die. Dermal stem cells lie in the hair papillae, around pericytes, and elsewhere among other dermal cells. These form pericytes, myoblasts, fibroblasts, chondrocytes, and other specialized dermal cells. Along with other signaling pathways, the Wnt signaling pathway controls stem cell fate. Wnt signals enlist two functionally and chemically different gene coactivators to direct the time and type of replicative divisions. Stem cells may help to heal wounds, repair damaged tissues, regenerate aged skin, and reinvigorate growth of skin, hair, nails, and mucous membranes.


Infant pointing: communication to cooperate or communication to learn?
Tomasello, Carpenter, and Liszkowski (2007) present compelling data to support the view that infant pointing, from the outset, is communicative and deployed in many of the same situations in which adults would ordinarily point for one another, either to share their interest in something, or to informatively help the other person. This commentary concurs with the view that infant pointing is a communicative gesture, but challenges their interpretation of the motives behind pointing in 12-month-olds. An alternative account is proposed, according to which infant pointing is neither declarative nor imperative, but interrogative, and rather than being driven by the motive to share or help, it may serve a powerful cultural learning mechanism by which infants can obtain information from knowledgeable adults.


Self-perceived Fracture Risk in the Global Longitudinal Study of Osteoporosis in Women: Its Correlates and Relationship with Bone Microarchitecture.
The purpose of this study is to examine correlates of self-perceived fracture risk (SPR) and relationships between SPR and subsequent bone density and microarchitecture in the UK arm of the Global Longitudinal Study of Osteoporosis in Women. 3912 women completed baseline questionnaires detailing medical history and SPR; 492 underwent HRpQCT scans of the radius and tibia and DXA scans of total body, hip, femoral neck and lumbar spine a median of 7.5 years later. Correlates of SPR were examined and a cluster analysis of potential predictors of SPR performed. SPR in relation to HRpQCT and aBMD parameters was examined using linear regression with and without adjustment for anthropometric, demographic and lifestyle covariates. Mean (SD) baseline age was 69.0 (9.0) years; 56.6% reported a similar SPR; 28.6% lower SPR; 14.9% higher SPR compared to women of similar age. In mutually-adjusted analysis, higher SPR was associated (p < 0.05) with: lower physical activity and educational attainment; use of anti-osteoporosis medications (AOM) and calcium supplements; greater number of falls in the previous year; history of fracture since aged 45; family history of hip fracture; and increased comorbidity. Higher SPR, history of fracture, and use of AOM, calcium and vitamin D clustered together. Even after adjustments that included AOM use, higher SPR was associated with: lower radial trabecular volumetric density and number, and higher trabecular separation; lower tibial cortical area and trabecular volumetric density; and lower aBMD at the femoral neck. Despite greater AOM use, women with higher baseline SPR had poorer subsequent bone health.


Precise algorithms to compute surface correlation functions of two-phase heterogeneous media and their applications.
The quantitative characterization of the microstructure of random heterogeneous media in d-dimensional Euclidean space R^{d} via a variety of n-point correlation functions is of great importance, since the respective infinite set determines the effective physical properties of the media. In particular, surface-surface F_{ss} and surface-void F_{sv} correlation functions (obtainable from radiation scattering experiments) contain crucial interfacial information that enables one to estimate transport properties of the media (e.g., the mean survival time and fluid permeability) and complements the information content of the conventional two-point correlation function. However, the current technical difficulty involved in sampling surface correlation functions has been a stumbling block in their widespread use. We first present a concise derivation of the small-r behaviors of these functions, which are linked to the mean curvature of the system. Then we demonstrate that one can reduce the computational complexity of the problem, without sacrificing accuracy, by extracting the necessary interfacial information from a cut of the d-dimensional statistically homogeneous and isotropic system with an infinitely long line. Accordingly, we devise algorithms based on this idea and test them for two-phase media in continuous and discrete spaces. Specifically for the exact benchmark model of overlapping spheres, we find excellent agreement between numerical and exact results. We compute surface correlation functions and corresponding local surface-area variances for a variety of other model microstructures, including hard spheres in equilibrium, decorated "stealthy" patterns, as well as snapshots of evolving pattern formation processes (e.g., spinodal decomposition). It is demonstrated that the precise determination of surface correlation functions provides a powerful means to characterize a wide class of complex multiphase microstructures.


Socioeconomic Position and Antidepressant Use as Predictors of Coronary Heart Disease Mortality: A Population-Based Registry Study of 362,271 Finns.
The interplay between depression and socioeconomic position (SEP) in predicting cardiovascular outcomes has rarely been examined. We investigated whether SEP modified the effect of antidepressant use on coronary heart disease (CHD) mortality. The data consisted of an 11% random sample of the Finnish population aged 40 to 79 years at the end of 1999 with an oversample of 80% of those who died in 2000 to 2007. Participants free of CHD at baseline (n = 362,271) were followed up for CHD mortality in 2000 to 2007. SEP was assessed via registry-based information on education, occupational position, and income. Antidepressant use served as a proxy for depression and was derived from registry data on prescription medication purchases in the 5-year period preceding baseline. Age- and sex-adjusted Cox regression models with sampling weights were used. Individuals with antidepressant purchases in any year 1995 to 1999 had a higher risk of CHD deaths (hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.62-1.75) than did those without purchases. Basic level of education (HR = 2.09, 95% CI = 2.01-2.17), blue-collar occupations (HR = 1.70, 95% CI = 1.65-1.75), and the lowest income tertile (HR = 2.79, 95% CI = 2.69-2.91) were related to increased relative risks for CHD mortality. No significant (p < .05) interactions emerged between the SEP indicators and antidepressant purchases indicating that the effect of antidepressant use on the relative risk for CHD was similar across varying levels of SEP. Our study demonstrates that in a country with tax-funded universal health care services, low SEP does not exacerbate the adverse effects of depression-as measured by antidepressant treatment-on cardiovascular health.


The protein-protein interaction map of Helicobacter pylori.
With the availability of complete DNA sequences for many prokaryotic and eukaryotic genomes, and soon for the human genome itself, it is important to develop reliable proteome-wide approaches for a better understanding of protein function. As elementary constituents of cellular protein complexes and pathways, protein-protein interactions are key determinants of protein function. Here we have built a large-scale protein-protein interaction map of the human gastric pathogen Helicobacter pylori. We have used a high-throughput strategy of the yeast two-hybrid assay to screen 261 H. pylori proteins against a highly complex library of genome-encoded polypeptides. Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome. The determination of a reliability score for every single protein-protein interaction and the identification of the actual interacting domains permitted the assignment of unannotated proteins to biological pathways.


Pre-hospital assessment with ultrasound in emergencies: implementation in the field.
Point-of-care ultrasound (US) is a proven diagnostic imaging tool in the emergency department (ED). Modern US devices are now more compact, affordable and portable, which has led to increased usage in austere environments. However, studies supporting the use of US in the prehospital setting are limited. The primary outcome of this pilot study was to determine if paramedics could perform cardiac ultrasound in the field and obtain images that were adequate for interpretation. A secondary outcome was whether paramedics could correctly identify cardiac activity or the lack thereof in cardiac arrest patients. We performed a prospective educational study using a convenience sample of professional paramedics without ultrasound experience. Eligible paramedics participated in a 3-hour session on point-of-care US. The paramedics then used US during emergency calls and saved the scans for possible cardiac complaints including: chest pain, dyspnea, loss of consciousness, trauma, or cardiac arrest. Four paramedics from two distinct fire stations enrolled a total of 19 unique patients, of whom 17 were deemed adequate for clinical decision making (89%, 95%CI 67%-99%). Paramedics accurately recorded 17 cases of cardiac activity (100%, 95%CI 84%-100%) and 2 cases of cardiac standstill (100%, 95%CI 22%-100%). Our pilot study suggests that with minimal training, paramedics can use US to obtain cardiac images that are adequate for interpretation and diagnose cardiac standstill. Further large-scale clinical trials are needed to determine if prehospital US can be used to guide care for patients with cardiac complaints.


Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer.
Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients.


Miniaturized movable contactless conductivity detection cell for capillary electrophoresis.
A miniaturized capacitively coupled contactless conductivity detector (mini-C(4)D) cell has been designed which is small enough to allow it to slide along the effective capillary length inside the capillary cassette of an Agilent capiillary electrophoresis system (CE) (or other CE brand of similar construction), including the possibility of positioning it close to the point of optical detection (4 cm), or even putting two such detector cells in one cassette. The cell was tested and the performance characteristics (noise, sensitivity, and peak width) were compared with those obtained with the previously used large C(4)D cell. No significant differences were observed. The mini-C(4)D was used in simultaneous separations of common cations and anions where its advantage over a larger C(4)D cell is the ability to vary the point of detection with the mini-C(4)D cell continuously at any point along the capillary length, so that the optimum apparent selectivity can be chosen. Other applications include providing a convenient second point of detection in addition to photometric detection, such as to measure accurately the linear velocity of a zone, or to allow placement of two mini-C(4)D cells in one capillary cassette simultaneously.


A comparison of conventional and minimally invasive multilevel surgery for children with diplegic cerebral palsy.
To compare changes in gait kinematics and walking speed 24 months after conventional (C-MLS) and minimally invasive (MI-MLS) multilevel surgery for children with diplegic cerebral palsy (CP). A retrospective analysis of 19 children following C-MLS, with mean age at surgery of 12 years five months (seven years ten months to 15 years 11 months), and 36 children following MI-MLS, with mean age at surgery of ten years seven months (seven years one month to 14 years ten months), was performed. The Gait Profile Score (GPS) and walking speed were collected preoperatively and six, 12 and 24 months postoperatively. Type and frequency of procedures as part of MLS, surgical adverse events, and subsequent surgery were recorded. In both groups, GPS improved from the preoperative gait analysis to the six-month assessment with maintenance at 12 and 24 months postoperatively. While reduced at six months in both groups, walking speed returned to preoperative speed by 12 months. The overall pattern of change in GPS and walking speed was similar over time following C-MLS and MI-MLS. There was a median of ten procedures per child as part of both C-MLS (interquartile range (IQR) 8.0 to 11.0) and MI-MLS (IQR 7.8 to 11.0). Surgical adverse events occurred in seven (37%) and 13 (36%) children, with four (21%) and 13 (36%) patients requiring subsequent surgery following C-MLS and MI-MLS, respectively. This study indicates similar improvements in gait kinematics and walking speed 24 months after C-MLS and MI-MLS for children with diplegic CP. Cite this article: Bone Joint J 2021;103-B(1):192-197.


Capillary electrophoresis with capacitively coupled contactless conductivity detection for the determination of urinary ethylmalonic acid for the diagnosis of ethylmalonic aciduria.
Ethylmalonic acid is a metabolic organic acid, and its accumulation in urine is diagnostic of ethylmalonic aciduria. In this study, a simple and fast method employing capillary electrophoresis equipped with capacitively coupled contactless conductivity detection was developed for the detection of ethylmalonic acid in urine samples. The optimized electrophoretic separation was performed in 50 mmol/L 2-(N-morpholino)ethanesulfonic acid solution, buffered at a pH of 6.5, and contained 0.13 mmol/L cetyltrimethylammonium bromide as an electroosmotic modifier. Electrophoresis was run at 28 kV in reversed polarity. The linear range of ethylmalonic acid concentration was between 1 and 100 mg/L with a regression coefficient of 0.9998. This method had good intra- and interday precision with <5% relative standard deviations. The detection limit (signal-to-noise ratio = 3) and the quantification limit (signal-to-noise ratio = 10) values were 0.139 and 0.466 mg/L, respectively. Using our optimized conditions, the method was successfully employed for the detection of ethylmalonic acid in urine sample of ethylmalonic aciduria patient.


Rap1 activation plays a regulatory role in pancreatic amylase secretion.
Rap1 is a member of the Ras superfamily of small GTP-binding proteins and is localized on pancreatic zymogen granules. The current study was designed to determine whether GTP-Rap1 is involved in the regulation of amylase secretion. Rap1A/B and the two Rap1 guanine nucleotide exchange factors, Epac1 and CalDAG-GEF III, were identified in mouse pancreatic acini. A fraction of both Rap1 and Epac1 colocalized with amylase in zymogen granules, but only Rap1 was integral to the zymogen granule membranes. Stimulation with cholecystokinin (CCK), carbachol, and vasoactive intestinal peptide all induced Rap1 activation, as did calcium ionophore A23187, phorbol ester, forskolin, 8-bromo-cyclic AMP, and the Epac-specific cAMP analog 8-pCPT-2'-O-Me-cAMP. The phospholipase C inhibitor U-73122 abolished carbachol- but not forskolin-induced Rap1 activation. Co-stimulation with carbachol and 8-pCPT-2'-O-Me-cAMP led to an additive effect on Rap1 activation, whereas a synergistic effect was seen on amylase release. Although the protein kinase A inhibitor H-89 abolished forskolin-stimulated CREB phosphorylation, it did not modify forskolin-induced GTP-Rap1 levels, excluding PKA participation. Overexpression of Rap1 GTPase-activating protein, which blocked Rap1 activation, reduced the effect of 8-bromo-cyclic AMP, 8-pCPT-2'-O-Me-cAMP, and vasoactive intestinal peptide on amylase release by 60% and reduced CCK- as well as carbachol-stimulated pancreatic amylase release by 40%. These findings indicate that GTP-Rap1 is required for pancreatic amylase release. Rap1 activation not only mediates the cAMP-evoked response via Epac1 but is also involved in CCK- and carbachol-induced amylase release, with their action most likely mediated by CalDAG-GEF III.


Fine-Grained Mapping of Cortical Somatotopies in Chronic Complex Regional Pain Syndrome.
It has long been thought that severe chronic pain conditions, such as complex regional pain syndrome (CRPS), are not only associated with, but even maintained by a reorganization of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations in CRPS patients, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used fMRI to characterize the S1 representation of the affected and unaffected hand in humans (of either sex) with unilateral CRPS. The cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable with those of both the unaffected hand and healthy controls. We found no differential relation between affected versus unaffected hand map measures and clinical measures (pain severity, upper limb disability, disease duration). Thus, if any map reorganization occurs, it does not appear to be directly related to pain and disease severity. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to "restore" somatotopic representations to treat pain.SIGNIFICANCE STATEMENT This study shows that the spatial map of the fingers in somatosensory cortex is largely preserved in chronic complex regional pain syndrome (CRPS). These findings challenge the treatment rationale for restoring somatotopic representations in complex regional pain syndrome patients.


Modeling deep ocean shipping noise in varying acidity conditions.
Possible future changes of ambient shipping noise at 0.1-1 kHz in the North Pacific caused by changing seawater chemistry conditions are analyzed with a simplified propagation model. Probable decreases of pH would cause meaningful reduction of the sound absorption coefficient in near-surface ocean water for these frequencies. The results show that a few decibels of increase may occur in 100 years in some very quiet areas very far from noise sources, with small effects closer to noise sources. The use of ray physics allows sound energy attenuated via volume absorption and by the seafloor to be compared.


A comparative genomics screen identifies a Sinorhizobium meliloti 1021 sodM-like gene strongly expressed within host plant nodules.
We have used the genomic data in the Integrated Microbial Genomes system of the Department of Energy's Joint Genome Institute to make predictions about rhizobial open reading frames that play a role in nodulation of host plants. The genomic data was screened by searching for ORFs conserved in α-proteobacterial rhizobia, but not conserved in closely-related non-nitrogen-fixing α-proteobacteria. Using this approach, we identified many genes known to be involved in nodulation or nitrogen fixation, as well as several new candidate genes. We knocked out selected new genes and assayed for the presence of nodulation phenotypes and/or nodule-specific expression. One of these genes, SMc00911, is strongly expressed by bacterial cells within host plant nodules, but is expressed minimally by free-living bacterial cells. A strain carrying an insertion mutation in SMc00911 is not defective in the symbiosis with host plants, but in contrast to expectations, this mutant strain is able to out-compete the S. meliloti 1021 wild type strain for nodule occupancy in co-inoculation experiments. The SMc00911 ORF is predicted to encode a "SodM-like" (superoxide dismutase-like) protein containing a rhodanese sulfurtransferase domain at the N-terminus and a chromate-resistance superfamily domain at the C-terminus. Several other ORFs (SMb20360, SMc01562, SMc01266, SMc03964, and the SMc01424-22 operon) identified in the screen are expressed at a moderate level by bacteria within nodules, but not by free-living bacteria. Based on the analysis of ORFs identified in this study, we conclude that this comparative genomics approach can identify rhizobial genes involved in the nitrogen-fixing symbiosis with host plants, although none of the newly identified genes were found to be essential for this process.


Fabrication of highly modulable fibrous 3D extracellular microenvironments.
Three-dimensional (3D) in vitro scaffolds that mimic the irregular fibrous structures of in vivo extracellular matrix (ECM) are critical for many important biological applications. However, structural properties modulation of fibrous 3D scaffolds remains a challenge. Here, we report the first highly modulable 3D fibrous scaffolds self-assembled by high-aspect-ratio (HAR) microfibers. The scaffolds structural properties can be easily tailored to incorporate various physical cues, including geometry, stiffness, heterogeneity and nanotopography. Moreover, the fibrous scaffolds are readily and accurately patterned on desired locations of the substrate. Cell culture exhibits that our scaffolds can elicit strong bidirectional cell-material interactions. Furthermore, a functional disparity between the two-dimensional substrate and our 3D scaffolds is identified by cell spreading and proliferation data. These results prove the potential of the proposed scaffold as a biomimetic extracellular microenvironment for cell study.


Electroacoustic miniaturized DNA-biosensor.
A micrometer-sized electroacoustic DNA-biosensor was developed. The device included a thin semi-crystalline polyethylene terephthalate (PET) dielectric layer with two Ag microband electrodes on one side and a DNA thiol-labeled monolayer adsorbed on a gold surface on the other. A resonance wave was observed at 29 MHz with a network analyzer, upon AC voltage application between the two Ag electrodes, corresponding to electromechanical coupling induced by molecular dipoles of the PET polymer chain in the dielectric layer. It was found that the device size and geometry were well adapted to detect DNA hybridization, by measuring the capacity of the resonance response evolution: hybridization induced polarization of the dielectric material that affected the electromechanical coupling established in the dielectric layer. The 0.2 mm(2) sensor sensitive area allows detection in small volumes and still has higher detection levels for bioanalytical applications, the non-contact configuration adopted avoids electric faradic reactions that may damage biosensor sensitive layers, and finally, PET is a costless raw material, easy to process and well adapted for large scale production. The well-balanced technological and economic advantages of this kind of device make it a good candidate for biochip integration.


Advances in diffusion MRI acquisition and processing in the Human Connectome Project.
The Human Connectome Project (HCP) is a collaborative 5-year effort to map human brain connections and their variability in healthy adults. A consortium of HCP investigators will study a population of 1200 healthy adults using multiple imaging modalities, along with extensive behavioral and genetic data. In this overview, we focus on diffusion MRI (dMRI) and the structural connectivity aspect of the project. We present recent advances in acquisition and processing that allow us to obtain very high-quality in-vivo MRI data, whilst enabling scanning of a very large number of subjects. These advances result from 2 years of intensive efforts in optimising many aspects of data acquisition and processing during the piloting phase of the project. The data quality and methods described here are representative of the datasets and processing pipelines that will be made freely available to the community at quarterly intervals, beginning in 2013.


Hyperthermic intraoperative intrapleural chemotherapy and surgical cytoreduction as part of multimodal treatment of malignant pleural mesothelioma - case report M. Szkorupa1, D. Klos1, J. Chudacek1, J. Hanuliak1, M. Stasek1, O. Fischer2, R. Lemstrova3.
Malignant pleural mesothelioma is one of the most aggressive malignancies with a very poor prognosis. Multimodal treatment consisting of three modalities - chemotherapy, radiotherapy and cytoreductive surgery is optimal. The use of new therapeutic modalities, such as hyperthermic intraoperative intrapleural chemotherapy or photodynamic therapy can improve the current results of mesothelioma treatment. Combined hyperthermic intraoperative chemotherapy and cytoreductive surgery as part of multimodal therapy of malignant mesothelioma has been used since 2017 at the 1st Department of Surgery of University Hospital Olomouc. The authors report the case of a 47-year-old man with malignant epithelioid mesothelioma of the left pleural cavity. Following neoadjuvant chemotherapy, this patient underwent extrapleural pneumonectomy with intraoperative intracavitary hyperthermic chemotherapy. The postoperative period was complicated by circulatory instability and later by tension fluidothorax with signs of heart failure. Currently, 8 months have elapsed from the surgery and the patient remains without any signs of recurrence.


The results of Hodgkin lymphoma treatment in children in the period 1997-2006.
In this paper we present the study of chemotherapy and radiotherapy treatment success in children suffering from Hodgkin's disease (HD) that were treated at Hematology-oncology Department of Pediatric Clinic in Sarajevo. In retrospective study we followed all patients with HD aged 0-15 who were diagnosed with and treated for HD at Pediatric Clinic in Sarajevo over the last 10 years (1st of January 1997 - 31st of December 2006). Until 2000 we used combination of chemotherapy and radiotherapy according to UKCCSG HD 9201 treatment protocol, and after the year 2000 protocol UKCCSG HD 2000 (ChlVPP / ABVD) was applied. The total number of the treated children 33. There were 17 boys (51,51 %) and 16 girls (48,49 %). In 10 patients (30,3 %) we found II A stage of HD, in 4 (12,1 %) II B stage of HD, in 6 children (18,8 %) stage III A, in 4 children (12,1 %) stage III B, in 4 children (12,1 %) stage IV A and in 5 (15,1 %) stage IV B. In 7 patients (21,2 %) relapse occurred, which demanded more aggressive chemotherapeutic treatment and radiotherapy too; while for 4 patients (12,1 %) in combination with bone marrow transplantation. Three patients (9,0 %) died. There are 30 children (91,0 %) who are alive and in either 1st or 2nd remission phase of HD. Secondary malignancies did not occur in any of the patients. Although many patients (58,1%) were diagnosed in an advanced stage of illness (III and IV) the results of HD therapy at Pediatric Clinic in Sarajevo are comparable to those in other European centers.


The restriction scaffold problem.
Most shotgun sequencing projects undergo a long and costly phase of finishing, in which a partial assembly forms several contigs whose order, orientation, and relative distance is unknown. We propose here a new technique that supplements the shotgun assembly data by experimentally simple and commonly used complete restriction digests of the target. By computationally combining information from the contig sequences and the fragment sizes measured for several different enzymes, we seek to form a "scaffold" on which the contigs will be placed in their correct orientation, order, and distance. We give a heuristic search algorithm for solving the problem and report on promising preliminary simulation results. The key to the success of the search scheme is the very rapid solution of two time-critical subproblems that are solved to optimality in linear time. Our simulations indicate that with noise levels of some 3% relative error in measuring fragment sizes, using six enzymes, most datasets of 13 contigs spanning 300kb can be correctly ordered, and the remaining ones have most of their pairs of neighboring contigs correct. Hence, the technique has a potential to provide real help to finishing. Even without closing all gaps, the ability to order and orient the contigs correctly makes the partial assembly both more accessible and more useful for biologists.


Analysis of the Medical Assistance in Dying Cases in Ontario: Understanding the Patient Demographics of Case Uptake in Ontario since the Royal Assent and Amendments of Bill C-14 in Canada.
On June 17, 2016, the Canadian government legalized medical assistance in dying (MAID) across the country by giving Royal Assent to Bill C-14. This Act made amendments to the Criminal Code and other Acts relating to MAID, allowing physicians and nurse practitioners to offer clinician-administered and self-administered MAID in conjunction with pharmacists being able to dispense the necessary medications. The eligibility criteria for MAID indicates that the individual 1) must be a recipient of publicly funded health services in Canada, 2) be at least 18 years of age, 3) be capable of health-related decision-making, and 4) has a grievous and irremediable medical condition. Because this is a new practice in Canadian health care, there are no published Canadian statistics on MAID cases to date, and this paper constitutes the first analysis of MAID cases in both the province of Ontario and Canada. Internationally, there are only a few jurisdictions with similar legislation already in place (US, the Netherlands, Belgium, Luxembourg, Switzerland, Columbia, Japan, and the United Kingdom). The published statistics on MAID cases from these jurisdictions were reviewed and used to establish the current global practices and demographics of MAID and will provide useful comparisons for Canada. This analysis will 1) outline the Canadian legislative approach to MAID, 2) provide an understanding of which patient populations in Ontario are using MAID and under what circumstances, and 3) determine if patterns exist between the internationally published MAID patient demographics and the Canadian MAID data. Selected patient demographics of the first 100 MAID cases in Ontario were reviewed and analyzed using anonymized data obtained from the Office of the Chief Coroner for Ontario so that an insight into the provision of MAID in Ontario could be obtained. Demographic factors such as age, sex, the primary medical diagnosis that prompted the request for MAID, the patient rationale for making a MAID request, the place where MAID was administered, the nature of MAID drug regimen used, and the status/specialty of medical personnel who administered the MAID drug regimen were analyzed. The analysis revealed that the majority of the first 100 MAID recipients were older adults (only 5.2% of patients were aged 35-54 years, with no younger adults between ages 18-34 years) who were afflicted with cancer (64%) and had opted for clinician-administered MAID (99%) that had been delivered in either a hospital (38.8%) or private residence (44.9%). Although the cohort was small, these Ontario MAID demographics reflect similar observations as those published internationally, but further analysis of both larger and annual case uptake in both Ontario and Canada will be conducted as the number of cases increases.


Effect of pain neuroscience education and dry needling on chronic elbow pain as a result of cyberchondria: a case report.
This case report describes a 31-year-old male who presented with complaints of chronic pain in his right elbow. Detailed subjective examination revealed that the patient had searched Google for extensive online information relating to his pain, ultimately self-labeling with various diagnoses. After researching in YouTube, the patient self-treated with ice, exercises, neural mobilization, self-massage and taping, all resulting in a failed outcome. Clinical findings revealed trigger points in his right brachioradialis muscle with added symptoms of central pain. This is a potential first-time description of physical therapy management of brachioradialis myofascial pain syndrome with superadded central pain caused as a result of cyberchondria where the patient used the Internet for arriving at a wrong self-diagnosis and incorrect self-treatment with failed or worsening pain outcomes leading to pain sustenance or chronicity. Physical therapy consisted of Pain Neuroscience Education, dry needling and exercise therapy. The patient was completely pain free and fully functional at the end of the sixth session, which was maintained at a one-month follow-up.


Sub-Poissonian shot noise of a high internal gain injection photon detector.
The noise performance of an infrared injection photon detector with very high internal gain was investigated at a wavelength of 1.55 mum. The devices showed sub-Poissonian shot noise with Fano factors around 0.55 at 0.7 V at room temperature. Optical to electrical conversion factors of 3000 electrons per absorbed photon were recorded at 0.7 V. The change in noise-equivalent power with respect to bias voltage was evaluated. The optical to electrical conversion factor and Fano factor were measured under increasing illumination and compared to theoretical expectations.


A novel decision aid to help plan for serious illness: a multisite randomized trial.
Recent studies have shown substantial deficiencies in the quality or quantity (or both) of communication and decision-making during serious illness. We evaluated the efficacy of a novel decision support intervention, the Plan Well Guide, in increasing completion of a standard medical order form for advance medical care planning and improving decisional outcomes in nonacademic primary care settings. We conducted a randomized trial in 3 primary care practices in Lethbridge, Alberta in 2017-2018. We recruited "patients at high risk" referred by the primary care doctor who required establishment or review of their Goals of Care Designation (GCD). Enrolled patients were randomly allocated to receive the Plan Well Guide, delivered by a trained facilitator, or usual care. Eight to 12 weeks after the intervention, a research assistant blinded to intervention assignment contacted the patients in both groups by telephone to do a final outcome assessment. The primary outcome was completion of GCD forms; secondary outcomes included decisional conflict scores and ratings of satisfaction. A total of 123 patients (59 women [48.0%]; mean age 73.9 yr) were enrolled, 66 in the intervention arm and 57 in the usualcare arm; 119 patients completed the trial. After the intervention, GCD completion rates in the intervention and usual-care groups were 95.3% and 90.9%, respectively (risk difference [RD] 4%, 95% confidence interval [CI] -14% to 22%), and the rate of concordance between medical orders and expressed preferences on follow-up was 78% and 66%, respectively (RD 12%, 95% CI -7% to 30%). Significantly fewer patients in the intervention group than in the usual-care group had written medical orders for intensive care unit care and cardiopulmonary resuscitation (22 [34%] v. 33 [60%], RD -26%, 95% CI -42% to -8%). Patients in the intervention group had lower decisional conflict scores than those in the usual-care group (mean 30.9 v. 43.1, adjusted mean difference -12.0, 95% CI -23.2 to -0.8). Physicians considered patients in the intervention group to have lower decisional conflict than those in the usual-care group, although not significantly so (mean score 10.4 v. 14.9, adjusted mean difference -4.7, 95% CI -9.9 to 0.4) and spent less time with the former (mean 9.7 v. 13.2 min, adjusted mean difference -3.5, 95% CI -5.5 to -1.5 min). The decision-support intervention did not increase GCD completion rates but did seem to improve some aspects of decisional quality while reducing the physician's time to accomplish GCD decisions. Trial registration: ClinicalTrials.gov, no. NCT01297946.


Accuracy of gas analysis in lung function laboratories.
Fifty lung function laboratories in England and Wales analysed test gas mixtures of carbon monoxide and helium. Most of them also analysed mixtures of oxygen and carbon dioxide in nitrogen. The percentage accuracy of the results was within 1% of the expected value in only 14% of determinations of carbon monoxide concentration, 28% for carbon dioxide, 37% for helium, and 48% for oxygen. The accuracy of ratios of two concentrations of helium and carbon monoxide was better than that of the individual gas samples. Overall the variation in results between laboratories was wide, the coefficient of variation ranging from about 3% for analysis of helium to 9% for carbon dioxide. This variation affected the values calculated for carbon monoxide transfer factor, where 20% were in error by more than 5%, and for the calculated value of the respiratory exchange ratio, where the interlaboratory coefficient of variation was about 10%. Errors in analysis were due to unsatisfactory calibration of analysers; five oxygen analysers had large zero errors; five carbon monoxide analysers and one helium analyser had notably curvilinear calibration curves. Insufficient information was obtained to ascertain the nature of the errors in analysis of carbon dioxide. Given the improvements in instrumentation, these results are evidence for deterioration in analytical standards in lung function laboratories from the standards of 20 years ago.


EM visualization of transcription by RNA polymerase II: downstream termination requires a poly(A) signal but not transcript cleavage.
We have used EM visualization of active genes on plasmid vectors in Xenopus oocyte nuclei to investigate the relationship between poly(A) signals and RNA polymerase II transcription termination. Although a functional poly(A) signal is required for efficient termination, cotranscriptional RNA cleavage at the poly(A) site is not. Furthermore, the phenomena of termination and cotranscriptional RNA cleavage can be uncoupled, and the efficiency of both varies independently on different copies of the same plasmid template in the same oocyte nucleus. The combined observations are consistent with a scenario in which there is template-specific addition to Pol II (presumably at the promoter) of elongation and/or RNA processing factors, which are altered upon passage through a poly(A) signal, resulting in termination and, in some cases, cotranscriptional RNA cleavage.


Identifying diffusion patterns of research articles on Twitter: A case study of online engagement with open access articles.
The growing presence of research shared on social media, coupled with the increase in freely available research, invites us to ask whether scientific articles shared on platforms like Twitter diffuse beyond the academic community. We explore a new method for answering this question by identifying 11 articles from two open access biology journals that were shared on Twitter at least 50 times and by analyzing the follower network of users who tweeted each article. We find that diffusion patterns of scientific articles can take very different forms, even when the number of times they are tweeted is similar. Our small case study suggests that most articles are shared within single-connected communities with limited diffusion to the public. The proposed approach and indicators can serve those interested in the public understanding of science, science communication, or research evaluation to identify when research diffuses beyond insular communities.


Time of day type of food--relation to mood and hunger during 24 hours of constant conditions.
A six-day high-carbohydrate meal (HC; 65 E% (energy percent) carbohydrates, 20 E% fat and 15 E% protein) and a six-day high-fat meal (HF; 40 E% carbohydrates, 45 E% fat and 15 E% protein) were given to seven healthy subjects in a crossover design. On the last day subjects were kept awake for 24 hours in a metabolic laboratory while substrate utilisation and energy expenditure were measured by indirect calorimetry. The subjects were given isocaloric meals every four hours. Results showed that hunger decreased at night (F = 4.2, p < 0.05) and linearly increased after meal intake. Macronutrient composition (fat/carbohydrates) seemed to be of less importance for hunger. Hunger and thirst were found to be strongly associated with gastrointestinal substances, for hunger the strongest being a negative correlation with triacylglycerol (partial correlation = -0.39). It is suggested that it might not be necessary for shift workers to eat full portions at night but that satiation will occur with less food. Possibly lack of adjustment of nocturnal food intake might be one reason why overweight is common in shift work populations.


High-Performance Graphene-Fiber-Based Neural Recording Microelectrodes.
Fabrication of flexible and free-standing graphene-fiber- (GF-) based microelectrode arrays with a thin platinum coating, acting as a current collector, results in a structure with low impedance, high surface area, and excellent electrochemical properties. This modification results in a strong synergistic effect between these two constituents leading to a robust and superior hybrid material with better performance than either graphene electrodes or Pt electrodes. The low impedance and porous structure of the GF results in an unrivalled charge injection capacity of 10.34 mC cm-2 with the ability to record and detect neuronal activity. Furthermore, the thin Pt layer transfers the collected signals along the microelectrode efficiently. In vivo studies show that microelectrodes implanted in the rat cerebral cortex can detect neuronal activity with remarkably high signal-to-noise ratio (SNR) of 9.2 dB in an area as small as an individual neuron.


First Asian Report of Leaf Spot of Ambrosia trifida Caused by Septoria epambrosiae.
Ambrosia trifida L., known as giant ragweed, is native to North America and was introduced in Korea in the 1970s (4). It is now widely naturalized, and since 1999, has been designated as one of 11 most 'harmful nonindigenous plants' by the Korean Ministry of Environment because of its adverse effects on native plants. Various strategies to eradicate this noxious weed have been unsuccessful (4). In June 2008, leaf spot symptoms on this weed were found in Inje, Korea. Hundreds of giant ragweed growing along stream banks contained leaf spots with leaf yellowing and premature defoliation. Leaf lesions were 1 to 5 mm in diameter, angular to irregular, dark brown without a distinct margin, later becoming pallid with a brown margin. Between 2008 and 2011, the authors observed the same symptoms in Dongducheon, Yangku, Namyangju, and Pocheon, Korea. Voucher specimens have been housed in the herbarium of Korea University. Numerous black pycnidia were formed on the lesion. Pycnidia were amphigenous, globose, dark brown, ostiolate, and measured 80 to 130 μm in diameter. Conidia were filiform, straight to mildly curved, eguttulate, hyaline, 18 to 36 × 1.5 to 2.5 μm, one to three septate, subtruncate at the base, and tapering to a rounded apex. Single-conidial isolations onto potato dextrose agar formed dark grayish colonies. Pycnidia matured after 5 weeks when plates were incubated under fluorescent illumination for 12-h photoperiods at 25°C. On the basis of morphological and cultural characteristics, the fungus was identified as Septoria epambrosiae D.F. Farr (2). Three isolates were deposited in the Korean Agricultural Culture Collection (KACC). Preliminary morphological identification of the fungal isolates was confirmed by molecular data. The internal transcribed spacer (ITS) region of rDNA was amplified using the ITS1/ITS4 primers and sequenced. The resulting sequences of 449 bp obtained from the three isolates were identical to each other. They showed 100% similarity when compared with a sequence of S. epambrosiae (GenBank No. AF279582). The nucleotide sequence of a representative isolate (KACC43850) was deposited in GenBank (No. JN695498). Pathogenicity was confirmed by inoculating the leaves of three seedlings with a conidial suspension (~2 × 105 conidia/ml). Three noninoculated seedlings served as controls. Plants were maintained in a glasshouse at 100% relative humidity for 48 h. After 6 days, typical leaf spots, identical to the one observed in the field, started to develop on the leaves of the inoculated plants. No symptoms were observed on the control plants. The fungus was successfully reisolated from the symptomatic plants, fulfilling Koch's postulates. A leaf spot disease associated with S. epambrosiae has previously been recorded on A. artemisiifolia in Hungary (1-3) and A. trifida in North America (2,3). To our knowledge, this is the first report of S. epambrosiae on giant ragweed in Asia. Because of its potential as a biocontrol agent, further studies are needed. References: (1) G. Bohar and I. Schwarczinger. Plant Dis. 83:696, 1999. (2) D. F. Farr and L. A. Castlebury. Sydowia 53:81, 2001. (3) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , September 20, 2011. (4) S. M. Oh et al. Impacts of Invasive Alien Weeds and Control Strategies of Noxious Weeds in Korea. National Institute of Agricultural Science and Technology, Suwon, Korea, 2007.


The Stroke Impact Scale: validation in a UK setting and development of a SIS short form and SIS index.
The Stroke Impact Scale (SIS) covers 8 dimensions and a composite disability score. This study evaluates the SIS in the UK context, and develops a single index and an 8-item short form. Patients with a diagnosis of stroke were recruited through general practices in London and the North-West of England. Patients completed the SIS and the EQ-5D. Internal consistency of the SIS dimensions and the disability score ranged from α 0.86 to 0.95. Complete data were available on 73 questionnaires (48.34%). Factor analysis suggested the 8 domains could be aggregated into a single index. A short-form SIS (SF-SIS) index was created by summing 1 item per dimension. Selected items were those that most highly correlated with their respective domain score (ρ ranged from 0.77-0.94, P<0.001). The SF-SIS index scores were highly correlated with those gained from the parent form (ρ=0.98; P<0.001). The correlation of the SIS index and SF-SIS index with the EQ-5D was identical (ρ=0.83; P<0.001). The disability score, whether scored from the dimensions of the SIS, or relevant items on the SF-SIS, were highly correlated (ρ=0.97; P<0.001). The SIS covers aspects of health, which are of importance to stroke patients, and the dimensions were found to have high levels of internal consistency in the UK context. The amount of incomplete data suggests that the length of the questionnaire may present a substantial patient burden. In comparison to the parent form the SF-SIS can accurately provide the disability score and overall index score with considerable brevity.


Comforting measures described by staff working in paediatric units.
Aim Children with cancer identify staff members, who work with them in paediatric units, as their most important comforters. This study aimed to shed light on how those staff members deliver this comfort. Methods Semi-structured interviews were performed and the content then analysed. Nine families (n=9) and eight staff members (n=8) participated in the study. Findings The staff described caring for the children and the whole family. They implemented certain comforting measures with the child, and described how they provided support to parents. Staff described how they felt comforted by relating to the children they were caring for. Conclusion Staff working in paediatric units develop good relationships with children and parents and comfort them using methods described in the literature. The quality of the staff's positive relationships with the children marked all their actions.