Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline

Rationale: Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. Objective: In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. Methods: Attentional function in mice haploinsufficient for Map2k7 (Map2k7+/− mice) was investigated using the five-choice serial reaction time task (5-CSRTT). Results: Once stable performance had been achieved, Map2k7+/− mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline—a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia—signs of improvement in attentional performance were detected. Conclusions: Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline

Feedback methods for inverse simulation of dynamic models for engineering systems applications

Inverse simulation is a form of inverse modelling in which computer simulation methods are used to find the time histories of input variables that, for a given model, match a set of required output responses. Conventional inverse simulation methods for dynamic models are computationally intensive and can present difficulties for high-speed applications. This paper includes a review of established methods of inverse simulation,giving some emphasis to iterative techniques that were first developed for aeronautical applications. It goes on to discuss the application of a different approach which is based on feedback principles. This feedback method is suitable for a wide range of linear and nonlinear dynamic models and involves two distinct stages. The first stage involves design of a feedback loop around the given simulation model and, in the second stage, that closed-loop system is used for inversion of the model. Issues of robustness within closed-loop systems used in inverse simulation are not significant as there are no plant uncertainties or external disturbances. Thus the process is simpler than that required for the development of a control system of equivalent complexity. Engineering applications of this feedback approach to inverse simulation are described through case studies that put particular emphasis on nonlinear and multi-input multi-output models

Marine benthic flora and fauna of Gourdon Bay and the Dampier Peninsula in the Kimberley region of North-Western Australia

Surveys undertaken to characterise the marine benthic habitats along the Dampier Peninsula and further south at Gourdon Bay in the Kimberley region of Western Australia were augmented with epibenthic sled sampling of soft and hard bottom habitats. This paper describes the species collected, their biomass and relative abundance for the main groups of marine macrophytes and invertebrates. Five localities were surveyed; Gourdon Bay, Quondong Point to Coulomb Point, Carnot Bay to Beagle Bay, Perpendicular Head and Packer Island. Sampling was limited to fifteen epibenthic dredge operations from a range of habitat types and was designed to target the most common habitat types and to obtain species identifications of the most important species and those which typified different habitat types. Surveys covered a total of 1,350 m 2 of seabed in depths between 11 and 23m. We identified 415 taxa comprising: 1 seagrass, 43 algae, 52 sponges, 30 ascidians, 10 hydroids, 14 scleractinian corals, 52 other cnidarians, 69 crustaceans, 73 molluscs and 71 echinoderms. Despite the limited nature of the sampling, a significant number of new species, range extensions and new records for Western Australia and Australia were recorded. Within the algae, one range extension (Halimeda cf. cuneata f. digitata not previously recorded in Western Australia) and one possible new species of Areschougia were recorded. Two range extensions were present in the ascidians; the solitary ascidian Polycarpa cf. intonata has previously only been recorded in Queensland and Cnemidocarpa cf. radicosa only in temperate Australian waters. There were several range extensions for the crustacea, for example, the sponge crab, Tumidodromia dormia, has only been recorded in Queensland. One species of holothurian of the genus Phyllophorus could not be identified from the literature available and may represent a new species. Similarly, a small species of the echinoid Gymnechinus could possibly be a new species. The collections of hydroids, hard corals, crinoids and molluscs contained no new species or range extensions. There was difficulty in identification of some groups to species level due to the status of the current taxonomic literature (e.g. Cnidaria, Porifera and ascidians) and there may be a number of new species among the material collected. Among the anthozoa, there is at least one new species of Chromonephthea and potentially 10 range extensions to Western Australia. Sinularia cf. acuta and Chromonephthea curvata are both new records for Australia with both previously recorded in Indonesia only. Among the better known taxa (e.g. molluscs, echinoderms, corals), most of the taxa identified to species level have been recorded to occur throughout north-western Australia, however the diversity recorded in this study is less than other parts of the Kimberley and this is almost certainly a result of the small overall area sampled and the single method of collection utilised. The most important species on soft bottom habitats in terms of biomass was the heart urchin Breynia desorii (up to 326 g.m -2). Sponges were the dominant fauna by biomass (up to 620 g.m -2) on hard bottom habitats and biomass was dominated a by a few large cup and massive sponge species (e.g. Pione velans and two unidentified Spheciospongia). The biomass of other filter feeders, especially ascidians (e.g. Aplidium cf. crateriferum), soft corals (e.g. Chromonephthea spp.), gorgonians (e.g. Junceella fragilis and Dichotella gemmacea) was also high, indicating the importance of these groups in characterising hard bottom habitats. Although low in biomass, crinoids such as Comaster multifidus and Comatula pectinata were abundant in samples that included a high biomass of other filter feeders

Determining the Internal Validity of the Inventory of Reading Occupations: An Assessment Tool of Children’s Reading Participation

The Inventory of Reading Occupations (IRO) is an assessment tool of children’s reading participation. In this study, we used Rasch methods to determine the internal validity of the IRO. Participants included 192 typical and struggling readers from kindergarten to third grade from five different states in the United States. We analyzed the fit of each of the items in the 17 reading categories, the test items in the three dimensions of reading participation, and the contexts of reading in the IRO. Analysis indicated that the IRO items support the Rasch model of unidimensionality. Analysis also indicated that 1 of the 30 test items can be revised to strengthen test validity. Moreover, the analysis also suggested that the IRO is more useful for first- to third-grade students. This study provides evidence of internal validity of a useful tool to assess children’s reading participation

Can children's instructional gameplay activity be used as a predictive indicator of reading skills?

For children who may face reading difficulties, early intervention is a societal priority. However, early intervention requires early detection. While much research has approached the issue of identification through measuring component skills at single timepoints, an alternative is the utilisation of dynamic assessment. To this point, few initiatives have explored the potential for identification through progress data from play in digital literacy games. This study explored how well growth curves from progress data in a digital intervention can predict reading performance after gameplay compared to measuring component skills at a single timepoint (school entry). 137 six-year-old students played the digital Graphogame for 25 weeks. Latent growth curve analyses showed that variation in trajectories explained variation in literacy performance to a greater extent than risk status at school entry. Findings point to a potential for non-intrusive reading assessment in the application of a serious digital game in first grade

The forgotten '45 : Donald Dubh's rebellion in an archipelagic context

The final rebellion of Donald Dubh, heir to the forfeited MacDonald lordship of the Isles, is usually examined within the context of Highland rebellions that occurred in the half century after forfeiture. However, the factors that motivated the Islesmen to rise in rebellion in 1545 are multi-faceted and can only be fully understood by placing the rising in a wider context, which considers national and archipelagic events. The discussion that follows explores the reasons why the Islesmen, almost unanimously, entered into agreement with Henry VIII to attack Scotland from the west and why this endeavour failed. At the same time, the article highlights Henry’s recognition of the strategic importance of the west which led him into alliance with Donald Dubh and his supporters

How much of protein sequence space has been explored by life on Earth?

We suggest that the vastness of protein sequence space is actually completely explorable during the populating of the Earth by life by considering upper and lower limits for the number of organisms, genome size, mutation rate and the number of functionally distinct classes of amino acids. We conclude that rather than life having explored only an infinitesimally small part of sequence space in the last 4 Gyr, it is instead quite plausible for all of functional protein sequence space to have been explored and that furthermore, at the molecular level, there is no role for contingency

Increasing microbiological confirmation and changing epidemiology of meningococcal disease on Merseyside, England

ObjectivesTo determine, for the last 5 years in children on Merseyside with clinical meningococcal disease (MCD), the impact on diagnostic yield of newer bacteriologic methods; bacterial antigen detection (AD) and polymerase chain reaction (PCR).MethodsProspective data collection at Royal Liverpool Children's Hospital over two epochs: 1 September 1992 to 30 April 1994 (epoch A, n = 126) and 17 November 1997 to 15 September 1998 (epoch B, n = 85).ResultsEpoch Awas compared with epoch B. Diagnosis was confirmed by detection of meningococci in 78 of 126 (61.9%) versus 64 of 85 (75.3%, P = 0.04), but with a significantly lower rate of positive blood and cerebrospinal fluid culture in the later epoch. The proportion of cases receiving penicillin pretreatment was unchanged at 32%, but the proportion undergoing lumbar puncture decreased significantly. Median ages were higher in epoch B: 1.7 years versus 2.49 years (P = 0.013, Mann-Whitney). There was a significant increase in the proportion of cases due to serogroup C (14/78 (18%) versus 30/64 (46.9%), P = 0.001).ConclusionsCulture detection of meningococci from children with MCD has reduced, as less lumbar punctures are done. However, improved diagnosis by PCR and AD has increased microbiological confirmation overall. Serogroup C disease and the median age of cases continue to rise

Baseline neutrophil-lymphocyte ratio holds no prognostic value for esophageal and junctional adenocarcinoma in patients treated with neoadjuvant chemotherapy

BACKGROUND: Several studies have reported that neutrophil-lymphocyte ratio (NLR) can predict survival in esophageal and gastroesophageal junction adenocarcinoma, as it reflects systemic inflammation. Hence, we aimed to determine whether baseline NLR holds prognostic value for esophageal adenocarcinoma patients treated with neoadjuvant chemotherapy (nCT) followed by surgery. METHODS: We studied the data of 139 patients that received nCT before undergoing esophagectomy with curative intent, all identified from a prospectively maintained database (1998-2016). Pretreatment hematology reports were used to calculate the baseline NLR. A receiver operating characteristic curve (ROC-curve) was plotted to determine an optimal cutoff value. NLR quartiles were used to display possible differences between groups in relation to overall survival (OS) and disease-free survival (DFS) using the method of Kaplan-Meier. Cox regression analysis was performed to assess the prognostic value of NLR. RESULTS: The median OS and DFS times were 46 months (interquartile range [IQR]: 19-166) and 30 months (IQR: 13-166], respectively, for the entire cohort. The ROC-curve showed that NLR has no discriminating power for survival status (area under the curve = 0.462) and therefore no optimal cutoff value could be determined. There were no statistically significant differences in median OS times for NLR quartiles: 65 (Q1), 32 (Q2), 45 (Q3), and 46 months (Q4) (P = 0.926). Similarly, DFS showed no difference between quartile groups, with median survival times of 27 (Q1), 19 (Q2), 36 (Q3), and 20 months (Q4) (P = 0.973). Age, pN, pM, and resection margin were independent prognostic factors for both OS and DFS. On the contrary, NLR was not associated with OS or DFS in univariable and multivariable analyses. CONCLUSION: Baseline NLR holds no prognostic value for esophageal and gastroesophageal junction adenocarcinoma patients treated with nCT in this study, in contrast to other recently published papers. This result questions the validity of NLR as a reliable prognostic indicator and its clinical usefulness in these patients