The development and validation of a teacher-reported low-level classroom disruption scale (LLCD-S)

Low-level classroom disruption (LLCD) is characterised by pupils swinging on chairs, whispering or fidgeting in class. This paper provides initial data on the development and validation of the teacher-rated Low-Level Classroom Disruption Scale (LLCD-S), with two samples of primary school pupils. Exploratory factor analysis in Study 1 (N= 120) revealed one factor accounting for 61% of the variance; supported by confirmatory factor analysis in Study 2 (N= 274), with one factor accounting for 63% of the variance. Both studies reported high Cronbach’s alpha values of.82 and.93 respectively. The evidence supports LLCD being a unidimensional construct, measured by the eight item LLCD-S. Weak convergence validity was found between the LLCD-S and the Strengths and Difficulties Questionnaire’s (SDQ) externalising behaviours: conduct problems and hyperactivity. This preliminary evidence indicates that LLCD-S is a valid and reliable measure of low-level classroom disruption. Further research is needed to test the utility of the LLCD-S across different levels of education, cultures and as a pupil-reported measure

Rapid Visualisation of Microarray Copy Number Data for the Detection of Structural Variations Linked to a Disease Phenotype

Whilst the majority of inherited diseases have been found to be caused by single base substitutions, small insertions or deletions (<1Kb), a significant proportion of genetic variability is due to copy number variation (CNV). The possible role of CNV in monogenic and complex diseases has recently attracted considerable interest. However, until the development of whole genome, oligonucleotide micro-arrays, designed specifically to detect the presence of copy number variation, it was not easy to screen an individual for the presence of unknown deletions or duplications with sizes below the level of sensitivity of optical microscopy (3–5 Mb). Now that currently available oligonucleotide micro-arrays have in excess of a million probes, the problem of copy number analysis has moved from one of data production to that of data analysis. We have developed CNViewer, to identify copy number variation that co-segregates with a disease phenotype in small nuclear families, from genome-wide oligonucleotide micro-array data. This freely available program should constitute a useful addition to the diagnostic armamentarium of clinical geneticists

Robust diagnostic genetic testing using solution capture enrichment and a novel variant-filtering interface.

Targeted hybridization enrichment prior to next-generation sequencing is a widespread method for characterizing sequence variation in a research setting, and is being adopted by diagnostic laboratories. However, the number of variants identified can overwhelm clinical laboratories with strict time constraints, the final interpretation of likely pathogenicity being a particular bottleneck. To address this, we have developed an approach in which, after automatic variant calling on a standard unix pipeline, subsequent variant filtering is performed interactively, using AgileExomeFilter and AgilePindelFilter (http://dna.leeds.ac.uk/agile), tools designed for clinical scientists with standard desktop computers. To demonstrate the method's diagnostic efficacy, we tested 128 patients using (1) a targeted capture of 36 cancer-predisposing genes or (2) whole-exome capture for diagnosis of the genetically heterogeneous disorder primary ciliary dyskinesia (PCD). In the cancer cohort, complete concordance with previous diagnostic data was achieved across 793 variant genotypes. A high yield (42%) was also achieved for exome-based PCD diagnosis, underscoring the scalability of our method. Simple adjustments to the variant filtering parameters further allowed the identification of a homozygous truncating mutation in a presumptive new PCD gene, DNAH8. These tools should allow diagnostic laboratories to expand their testing portfolios flexibly, using a standard set of reagents and techniques

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Thin Current Sheet Behind the Dipolarization Front

We report a unique conjugate observation of fast flows and associated current sheet disturbances in the near-Earth magnetotail by MMS (Magnetospheric Multiscale) and Cluster preceding a positive bay onset of a small substorm at ∼14:10 UT, September 8, 2018. MMS and Cluster were located both at X ∼ −14 RE. A dipolarization front (DF) of a localized fast flow was detected by Cluster and MMS, separated in the dawn-dusk direction by ∼4 RE, almost simultaneously. Adiabatic electron acceleration signatures revealed from the comparison of the energy spectra confirm that both spacecraft encounter the same DF. We analyzed the change in the current sheet structure based on multi-scale multi-point data analysis. The current sheet thickened during the passage of DF, yet, temporally thinned subsequently associated with another flow enhancement centered more on the dawnward side of the initial flow. MMS and Cluster observed intense perpendicular and parallel current in the off-equatorial region mainly during this interval of the current sheet thinning. Maximum field-aligned currents both at MMS and Cluster are directed tailward. Detailed analysis of MMS data showed that the intense field-aligned currents consisted of multiple small-scale intense current layers accompanied by enhanced Hall-currents in the dawn-dusk flow-shear region. We suggest that the current sheet thinning is related to the flow bouncing process and/or to the expansion/activation of reconnection. Based on these mesoscale and small-scale multipoint observations, 3D evolution of the flow and current-sheet disturbances was inferred preceding the development of a substorm current wedge

Reconnection Inside a Dipolarization Front of a Diverging Earthward Fast Flow

We examine a Dipolarization Front (DF) event with an embedded electron diffusion region (EDR), observed by the Magnetospheric Multiscale (MMS) spacecraft on 08 September 2018 at 14:51:30 UT in the Earth's magnetotail by applying multi-scale multipoint analysis methods. In order to study the large-scale context of this DF, we use conjunction observations of the Cluster spacecraft together with MMS. A polynomial magnetic field reconstruction technique is applied to MMS data to characterize the embedded electron current sheet including its velocity and the X-line exhaust opening angle. Our results show that the MMS and Cluster spacecraft were located in two counter-rotating vortex flows, and such flows may distort a flux tube in a way that the local magnetic shear angle is increased and localized magnetic reconnection may be triggered. Using multi-point data from MMS we further show that the local normalized reconnection rate is in the range of R ∼ 0.16 to 0.18. We find a highly asymmetric electron in- and outflow structure, consistent with previous simulations on strong guide-field reconnection events. This study shows that magnetic reconnection may not only take place at large-scale stable magnetopause or magnetotail current sheets but also in transient localized current sheets, produced as a consequence of the interaction between the fast Earthward flows and the Earth's dipole field

Nowcasting pandemic influenza A/H1N1 2009 hospitalizations in the Netherlands

During emerging epidemics of infectious diseases, it is vital to have up-to-date information on epidemic trends, such as incidence or health care demand, because hospitals and intensive care units have limited excess capacity. However, real-time tracking of epidemics is difficult, because of the inherent delay between onset of symptoms or hospitalizations, and reporting. We propose a robust algorithm to correct for reporting delays, using the observed distribution of reporting delays. We apply the algorithm to pandemic influenza A/H1N1 2009 hospitalizations as reported in the Netherlands. We show that the proposed algorithm is able to provide unbiased predictions of the actual number of hospitalizations in real-time during the ascent and descent of the epidemic. The real-time predictions of admissions are useful to adjust planning in hospitals to avoid exceeding their capacity

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Enhanced recovery in colorectal surgery: a multicentre study

<p>Abstract</p> <p>Background</p> <p>Major colorectal surgery usually requires a hospital stay of more than 12 days. Inadequate pain management, intestinal dysfunction and immobilisation are the main factors associated with delay in recovery. The present work assesses the short and medium term results achieved by an enhanced recovery program based on previously published protocols.</p> <p>Methods</p> <p>This prospective study, performed at 12 Spanish hospitals in 2008 and 2009, involved 300 patients. All patients underwent elective colorectal resection for cancer following an enhanced recovery program. The main elements of this program were: preoperative advice, no colon preparation, provision of carbohydrate-rich drinks one day prior and on the morning of surgery, goal directed fluid administration, body temperature control during surgery, avoiding drainages and nasogastric tubes, early mobilisation, and the taking of oral fluids in the early postoperative period. Perioperative morbidity and mortality data were collected and the length of hospital stay and protocol compliance recorded.</p> <p>Results</p> <p>The median age of the patients was 68 years. Fifty-two % of the patients were women. The distribution of patients by ASA class was: I 10%, II 50% and III 40%. Sixty-four % of interventions were laparoscopic; 15% required conversion to laparotomy. The majority of patients underwent sigmoidectomy or right hemicolectomy. The overall compliance to protocol was approximately 65%, but varied widely in its different components. The median length of postoperative hospital stay was 6 days. Some 3% of patients were readmitted to hospital after discharge; some 7% required repeat surgery during their initial hospitalisation or after readmission. The most common complications were surgical (24%), followed by septic (11%) or other medical complications (10%). Three patients (1%) died during follow-up. Some 31% of patients suffered symptoms that delayed their discharge, the most common being vomiting or nausea (12%), dyspnoea (7%) and fever (5%).</p> <p>Conclusion</p> <p>The following of this enhanced recovery program posed no risk to patients in terms of morbidity, mortality and shortened the length of their hospital stay. Overall compliance to protocol was 65%. The following of this program was of benefit to patients and reduces costs by shortening the length of hospital stay. The implantation of such programmes is therefore highly recommended.</p