Log-mean linear models for binary data

This paper introduces a novel class of models for binary data, which we call log-mean linear models. The characterizing feature of these models is that they are specified by linear constraints on the log-mean linear parameter, defined as a log-linear expansion of the mean parameter of the multivariate Bernoulli distribution. We show that marginal independence relationships between variables can be specified by setting certain log-mean linear interactions to zero and, more specifically, that graphical models of marginal independence are log-mean linear models. Our approach overcomes some drawbacks of the existing parameterizations of graphical models of marginal independence

Dutch teacher beliefs on linguistic concepts and reflective judgement in grammar teaching

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Remodelling of gap junctions and connexin expression in diseased myocardium

Gap junctions form the cell-to-cell pathways for propagation of the precisely orchestrated patterns of current flow that govern the regular rhythm of the healthy heart. As in most tissues and organs, multiple connexin types are expressed in the heart: connexin43 (Cx43), Cx40 and Cx45 are found in distinctive combinations and relative quantities in different, functionally-specialized subsets of cardiac myocyte. Mutations in genes that encode connexins have only rarely been identified as being a cause of human cardiac disease, but remodelling of connexin expression and gap junction organization are well documented in acquired adult heart disease, notably ischaemic heart disease and heart failure. Remodelling may take the form of alterations in (i) the distribution of gap junctions and (ii) the amount and type of connexins expressed. Heterogeneous reduction in Cx43 expression and disordering in gap junction distribution feature in human ventricular disease and correlate with electrophysiologically identified arrhythmic changes and contractile dysfunction in animal models. Disease-related alterations in Cx45 and Cx40 expression have also been reported, and some of the functional implications of these are beginning to emerge. Apart from ventricular disease, various features of gap junction organization and connexin expression have been implicated in the initiation and persistence of the most common form of atrial arrhythmia, atrial fibrillation, though the disparate findings in this area remain to be clarified. Other major tasks ahead focus on the Purkinje/working ventricular myocyte interface and its role in normal and abnormal impulse propagation, connexin-interacting proteins and their regulatory functions, and on defining the precise functional properties conferred by the distinctive connexin co-expression patterns of different myocyte types in health and disease

Linguistic metaconcepts can improve grammatical understanding in L1 education evidence from a Dutch quasi-experimental study

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All relevant data are within the paper and its Supporting Information files. Data can also be found on the OSF repository at: DOI 10.17605/OSF.IO/EGKJD (https://osf.io/egkjd/?view_only=None).This mixed-method quasi-experimental study examined whether metaconceptual grammar teaching impacts on (a) students’ L1 grammatical understanding, (b) their ‘blind’ use of grammatical concepts and (c) their preference of using explicit grammatical concepts over everyday concepts in explaining grammatical problems. Previous research, involving single group pre-postintervention designs, found positive effects for metaconceptual interventions on secondary school students’ grammatical reasoning ability, although a negative side effect seemed to be that some students started using grammatical concepts ‘blindly’ (i.e., in an inaccurate way). While there are thus important clues that metaconceptual grammar teaching may lead to increased grammatical understanding, there is a great need for more robust empirical research. The current study, involving 196 Dutch 14-year old pre-university students, is a methodological improvement of previous work, adopting a switching replications design. Bayesian multivariate analyses indicate medium to large effects from the metaconceptual intervention on students’ grammatical understanding. The study found a similar effect of the intervention on students’ ability to use explicit grammatical concepts over everyday concepts in tackling grammatical problems. No evidence for increased ‘blind’ concept use as a negative byproduct of the intervention was found. Additional qualitative analyses of in-intervention tasks provided further evidence for the effectiveness of metaconceptual interventions, and seemed to indicate that cases of blind concept use, rather than being a negative side effect, might actually be part of a gradual process of students’ growing understanding of grammatical (meta)concepts. We discuss these findings in relation to previous work and conclude that linguistic metaconcepts can improve L1 grammatical understanding.Netherlands Organisation of Scientific Research (NWO

Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carbotplatin

Chemotherapy-induced cognitive impairment, known also as “chemobrain”, is a medical complication of cancer treatment that is characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem solving skills, and motor function. It is estimated that one-third of patients who undergo chemotherapy treatment will experience cognitive impairment. Alterations in the release and uptake of dopamine and serotonin, central nervous system neurotransmitters that play important roles in cognition, could potentially contribute to impaired intellectual performance in those impacted by chemobrain. To investigate how chemotherapy treatment affects these systems, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure dopamine and serotonin release and uptake in coronal brain slices containing the striatum and dorsal raphe nucleus, respectively. Measurements were taken from rats treated weekly with selected doses of carboplatin and from control rats treated with saline. Modeling the stimulated dopamine release plots revealed an impairment of dopamine release per stimulus pulse (80% of saline control at 5 mg/kg and 58% at 20 mg/kg) after 4 weeks of carboplatin treatment. Moreover, Vmax, the maximum uptake rate of dopamine, was also decreased (55% of saline control at 5 mg/kg and 57% at 20 mg/kg). Nevertheless, overall dopamine content, measured in striatal brain lysates by high performance liquid chromatography, and reserve pool dopamine, measured by FSCV after pharmacological manipulation, did not significantly change, suggesting that chemotherapy treatment selectively impairs the dopamine release and uptake processes. Similarly, serotonin release upon electrical stimulation was impaired (45% of saline control at 20 mg/kg). Measurements of spatial learning discrimination were taken throughout the treatment period and carboplatin was found to alter cognition. These studies support the need for additional neurochemical and behavioral analyses to identify the underlying mechanisms of chemotherapy-induced cognitive disorders

Influence of V5/6-His Tag on the Properties of Gap Junction Channels Composed of Connexin43, Connexin40 or Connexin45

HeLa cells expressing wild-type connexin43, connexin40 or connexin45 and connexins fused with a V5/6-His tag to the carboxyl terminus (CT) domain (Cx43-tag, Cx40-tag, Cx45-tag) were used to study connexin expression and the electrical properties of gap junction channels. Immunoblots and immunolabeling indicated that tagged connexins are synthesized and targeted to gap junctions in a similar manner to their wild-type counterparts. Voltage-clamp experiments on cell pairs revealed that tagged connexins form functional channels. Comparison of multichannel and single-channel conductances indicates that tagging reduces the number of operational channels, implying interference with hemichannel trafficking, docking and/or channel opening. Tagging provoked connexin-specific effects on multichannel and single-channel properties. The Cx43-tag was most affected and the Cx45-tag, least. The modifications included (1) Vj-sensitive gating of Ij (Vj, gap junction voltage; Ij, gap junction current), (2) contribution and (3) kinetics of Ij deactivation and (4) single-channel conductance. The first three reflect alterations of fast Vj gating. Hence, they may be caused by structural and/or electrical changes on the CT that interact with domains of the amino terminus and cytoplasmic loop. The fourth reflects alterations of the ion-conducting pathway. Conceivably, mutations at sites remote from the channel pore, e.g., 6-His-tagged CT, affect protein conformation and thus modify channel properties indirectly. Hence, V5/6-His tagging of connexins is a useful tool for expression studies in vivo. However, it should not be ignored that it introduces connexin-dependent changes in both expression level and electrophysiological properties

The impact of donor policies in Europe: a steady increase, but not everywhere

<p>Abstract</p> <p>Background</p> <p>Transplantable organs are scarce everywhere. Therefore, countries have developed policies to support the efficient use of potential donors. Nevertheless, the shortage of organs remains. Were these policies in vain? The aim of this study is to assess the impact of donor policies on donor procurement in 10 Western European countries from 1995 to 2005.</p> <p>Method</p> <p>To assess the impact of the donor policies we studied the conversion of potential donors into effectuated donors. 80% of the donors died from CVAs or a (traffic) accident. We considered these mortality rates to be a good proxy for potential donors. Here we call the conversion of potential donors into actual donors 'the donor efficiency rate by proxy'.</p> <p>Results</p> <p>The mortality rates for CVA and (traffic) accidents have decreased in the countries under study. At the same time, in most countries the donor efficiency rates have steadily increased. The variance in donor efficiency rates between countries has also increased from 1995 to 2005. Four countries introduced a new consent system or changed their existing system, without (visible) long-term effects.</p> <p>Conclusion</p> <p>The overall increase in donor efficiency means that the efforts to improve donor policies have paid off. However, substantial differences between countries were found. The success of donor policies in terms of the number of absolute donors is blurred by the success of policies on traffic safety and CVA treatment. It remains unclear which specific policy measures are responsible for the increase in donor efficiency rates. This increase is not related to having a presumed consent system. Furthermore, an analysis of countries that introduced a new consent system or changed their system showed no effect on donor efficiency.</p