Search

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, This work was supported by the Medical Research Council (G0901310) and the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z). This study was supported by the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London and by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust at King’s College London. Further support to EB: Mental Health Research UK’s John Grace QC award, BMA Margaret Temple grants 2016 and 2006, MRC—Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship, the NIHR Biomedical Research Centre at UCLH, and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King’s College London. Further support to co-authors: The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to CI). The BMA Margaret Temple grant 2016 to JT. A 2014 European Research Council Marie Curie award to A Díez-Revuelta. HI has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 747429. A Medical Research Council doctoral studentship to JH-S, IA-Z and AB. A Mental Health Research UK studentship to RM. VB is supported by a Wellcome Trust Seed Award in Science (200589/Z/16/Z). FWO Senior Clinical Fellowship to RvW. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organisations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Centre and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Groningen: University Medical Centre Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical centre The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en De Kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Centre Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). The Santander cohort was supported by Instituto de Salud Carlos III (PI020499, PI050427, PI060507), SENY Fundació (CI 2005-0308007), Fundacion Ramón Areces and Fundacion Marqués de Valdecilla (API07/011, API10/13). We thank Valdecilla Biobank for providing the biological PAFIP samples and associated data included in this study and for its help in the technical execution of this work; we also thank IDIVAL Neuroimaging Unit for its help in the acquisition and processing of imaging PAFIP data.

Multilingual learning and teaching have been receiving growing attention of late as many cities and states undergo significant demographic changes brought about by increasing levels of human migration. The onset of super‐diversity means that teachers often encounter students with very different language and cultural backgrounds in the classroom. This has created a new set of challenges and opportunities, especially concerning the teaching and learning of languages. As a result, research on language teaching and learning in super‐diverse contexts has acquired greater importance, yet the teaching of languages other than English (LOTE), specifically LOTE teacher beliefs and practices, has received comparatively little attention to date. To shed more light on teacher beliefs and practices as these concern the teaching of LOTEs to multilingual students, this study explored the extent to which 100 Arabic language teachers, working in UK‐curriculum secondary schools in the United Arab Emirates, used their students’ multilingualism as a resource during lessons and developed their self‐regulation and language awareness through specific activities. The findings regarding the participants’ efforts to develop their students’ self‐regulation and language awareness revealed an unexpected, negative correlation between their degree of multilingualism and their reported practices. publishedVersion

Sarcomas are one of the most difficult type of cancer to manage and treat because of their extremely heterogeneous molecular and morphological features. Despite the progress made over the years in the establishment of standard protocols for high and low grading/staging sarcoma patients, mostly with chemotherapy and/or radiotherapy, 50% of treated patients experience relapse episodes. Because of this, in the last 20 years, new therapeutic approaches for sarcoma treatment have been evaluated in preclinical and clinical studies. Among them, antibody-based therapies have been the most studied. Immunoconjugates consist of a carrier portion, frequently represented by an antibody, linked to a toxic moiety, i.e., a drug, toxin, or radionuclide. While the efficacy of immunoconjugates is well demonstrated in the therapy of hematological tumors and more recently also of epithelial ones, their potential as therapeutic agents against sarcomas is still not completely explored. In this paper, we summarize the results obtained with immunoconjugates targeting sarcoma surface antigens, considering both preclinical and clinical studies. To date, the encouraging results obtained in preclinical studies allowed nine immunoconjugates to enter clinical trials, demonstrating the validity of immunotherapy as a promising pharmacological tool also for sarcoma therapy.

Hyperprolactinemia is a known adverse drug reaction to antipsychotic treatment. Antipsychotic blood levels are influenced by cytochrome P450 enzymes, primarily CYP2D6. Variation in CYP450 genes may affect the risk of antipsychotic-induced hyperprolactinemia. We undertook a systematic review and meta-analysis to assess whether CYP2D6 functional genetic variants are associated with antipsychotic-induced hyperprolactinemia. The systematic review identified 16 relevant papers, seven of which were suitable for the meta-analysis (n = 303 participants including 134 extreme metabolisers). Participants were classified into four phenotype groups as poor, intermediate, extensive, and ultra-rapid metabolisers. A random effects meta-analysis was used and Cohen's d calculated as the effect size for each primary study. We found no significant differences in prolactin levels between CYP2D6 metabolic groups. Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia. However, statistical power is limited. Future studies with larger samples and including a range of prolactin-elevating drugs are needed.

Employing a qualitative design, this exploratory study examined the challenges and constraints encountered by foreign language teachers in Russia when using literature in their lessons in primary, secondary and tertiary education. Consisting of interviews with nine Russian EFL teachers, the study’s findings indicate that education policies, a strong focus on standardized testing, poor quality textbooks, and a lack of institutional support are not only hindering a wider adoption of literary texts as a language resource, but are also likely hampering language learning in students. The study presents policymakers, as well as school and university administrators, with insights into the structural issues that might be preventing foreign language teachers from more effectively integrating literature into their lessons, and offers recommendations that could help them to formulate policies and strategies that address these issues. Šis tyrimas paremtas nepublikuotais apklausos duomenimis, kuriuos autorius (2018) surinko tirdamas 140-ies Rusijos anglų kalbos mokytojų požiūrį į literatūrą kaip į kalbos mokymo(si) šaltinį. Remiantis pusiau struktūriniu interviu, išsamiai nagrinėjami konkretūs iššūkiai ir suvaržymai, kuriuos patiria Rusijos anglų kalbos mokytojai pagrindinėje, vidurinėje ir aukštojoje ugdymo pakopose, kai įtraukia literatūrą į savo pamokas (Rusijos švietimo ministerijai rekomenduojant). Šiam tyrimui buvo apklausti devyni Rusijos anglų kalbos mokytojai iš Maskvos mokyklų ir universitetų, su jais buvo susisiekta elektroniniu būdu per atitinkamus jų institucijų administracinius padalinius. Interviu duomenys patvirtino apklausos duomenis, susijusius su iššūkiais ir apribojimais, kuriuos patiria mokytojai, ir nuodugniau atskleidė šių apribojimų pobūdį. Devyni mokytojai ugdymo turinio reikalavimus, nuostatą gerai parengti mokinius standartizuotiems testams, žemos kokybės užsienio kalbos mokomąją medžiagą ir nepakankamą jų institucijų skatinimą įvardino kaip ribojančius jų gebėjimą efektyviai įtraukti literatūros komponentą į užsienio kalbos pamokas. Šis tyrimas yra reikšmingas, nes tai yra vienas iš nedaugelio tyrimų, kurie leidžia išsamiai išnagrinėti apribojimus, su kuriais susiduria anglų kalbos mokytojai Rusijoje, norėdami įtraukti literatūrą į savo pamokas; straipsnyje taip pat pateikiamos rekomendacijos, kaip įveikti šiuos apribojimus. Siekiama skatinti geresnį institucijų ir mokytojų bendradarbiavimą kuriant ir įgyvendinant užsienio kalbų ugdymo politiką, taip pat kuriant mokytojų rengimo programas, kurių tikslas – plėsti užsienio kalbų mokymo įvairovę ir perteikti visapusiškesnę kalbos mokymosi patirtį asmenims, besimokantiems pagrindinėje, vidurinėje ir aukštojoje ugdymo pakopose. publishedVersion

The “dysconnection hypothesis” of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition—that is, increased cortical excitability—in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis.

BACKGROUND: There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.AimsTo investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls. METHOD: Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls. RESULTS: Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest. CONCLUSIONS: Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.Declaration of interestR.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian. Funding: This work was funded by the Medical Research Council (G0901310), the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z), the European Union’s Seventh Framework Programme for research, technological development and demonstration (grant 602450). This study was also supported by the NIHR Biomedical Research Centre at University College London (mental health theme) and by the NIHR Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry – Kings College London. Further support: NHIR Academic Clinical fellowship awarded to M.S.C.. E.B. acknowledges research funding from: BMA Margaret Temple grants 2016 and 2006, MRC – Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry Kings College London. The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to C.I.). The BMA Margaret Temple grant 2016 to J. H.T. European Research Council Marie Curie award to A.D.-R. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental healthcare organisations. Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en de kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan Zorggroep, Prins Clauscentrum Sittard, RIAGG Roermond, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psychomedical center (The Hague). Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht, GGZ Centraal, Riagg Amersfoort and Delta. The sample from Spain was collected at the Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Carlos III Health Institute PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005- Orden sco/3246/2004, SENY Fundació Research Grant CI 2005-0308007 and Fundación Marqués de Valdecilla API07/011. The present data were obtained at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: MINECO Exp.: SAF2013-46292-R.

Background: The “dysconnection hypothesis” of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. We investigated intrinsic (self-)connectivity in a cortical hierarchy during a P300 experiment. We used Dynamic Causal Modeling to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Methods: Twenty-four patients with psychosis, 24 unaffected relatives, and 25 controls underwent EEG recordings during an auditory oddball paradigm. We analyzed 16 frontoparietal models (primary auditory, superior parietal, and superior frontal sources) and identified an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition. Results: The winning model included changes in connectivity at all 3 hierarchical levels. Patients showed decreased self-inhibition (ie, increased cortical excitability) in left superior frontal gyrus across task conditions, compared to unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets, relative to standard tones. Conclusion: We confirmed that both subjects with psychosis and their relatives show a context-independent loss of synaptic gain control at the highest levels of the hierarchy. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis.

This paper explores the situational factors that explain why crime in Bormla occurs in certain areas and not others. Bormla, one of the oldest cities in Malta, is the fifth crime hotspot on the Maltese Islands. The objective of this paper is to find out whether socio-demographic aspects and/or other contextual aspects are linked with the rate and type of crime that takes place within this city. A multi-method approach was adopted for the purposes of this paper. Statistics issued by the Malta police were analysed to find out which criminal offences occur there, and in which location. This analysis took place with the help of Geographic Information System (GIS) software. Qualitative and quantitative data collected through a needs assessment exercise conducted with a sample of Bormla respondents in 2009 and 2010 was also analysed to find out whether residents concurred with this official picture of what type of crime takes place there, and where it occurs. Residents were also asked whether they felt safe living in this crime hotspot, when and where they felt safe, and why., peer-reviewed

Terrorism is one of the fears that influenced the economic, political and security transformations of contemporary societies. The effects of terrorism can be traced back to ancient Greece and evolved en par with societies through the centuries. The anarchist ‘propaganda by deed’ methodology was followed by other terrorist movements later on in history, as well as in the modus operandi of the terrorist organization in the last decade. So the question remains, so now what’s next? The Internet and its ‘natural habitat’ gave the possibility to develop what has been recognized as cyber-terrorism. The services provided by the Internet allow terrorists to adopt an entrepreneur approach to their business. New products are quickly sought and customised to achieve defined goals like any other enterprise. The Internet allows terrorists to spread their message to a far wider audience than that permitted by other non-Internet environments. Cyber-terrorism evolved from being the support infrastructure necessary to commit an attack to the attack itself. This lethal cocktail kindles the need to rethink the economic, political and security strategies in order to mitigate the effects of cyber-terrorism.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by severe cognitive impairment that ultimately leads to death. Current drugs used in AD are acetylcholinesterase inhibitors and antagonists to the NMDA receptors. These drugs may only slightly improve cognitive functions but have only very limited impact on the clinical course of the disease. In the past several years, based on in vitro and in vivo studies in laboratory animals, natural antioxidants, such as resveratrol, curcumin and acetyl-L-carnitine have been proposed as alternative therapeutic agents for AD. An increasing number of studies demonstrated the efficacy of primary antioxidants, such as polyphenols, or secondary antioxidants, such as acetylcarnitine, to reduce or to block neuronal death occurring in the pathophysiology of this disorder. These studies revealed that other mechanisms than the antioxidant activities could be involved in the neuroprotective effect of these compounds. This paper discusses the evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms leading to the upregulation of vitagenes. Furthermore, future development of novel antioxidant drugs targeted to the mitochondria should result in effectively slowing disease progression. The association with new drug delivery systems may be desirable and useful for the therapeutic use of antioxidants in human neurodegenerative diseases.