A review of the aetiology and management of vocal behaviour in dementia

Vocal behaviour is a common form of agitation displayed by people with dementia. It refers to excessive screaming, abusive language, moaning, perseveration, and repetitive and inappropriate requests. The authors provide a literature review on this form of challenging behaviour, focusing on the aetiological factors and the available treatment options. Emphasis is put on a biopsychosocial approach. The aim of this article is to increase awareness of the condition in elderly nursing residences and hospitals, and to encourage best evidence-based practice.peer-reviewe

Ferroelectric-Domain-Patterning-Controlled Schottky Junction State in Monolayer MoS\u3csub\u3e2\u3c/sub\u3e

We exploit scanning-probe-controlled domain patterning in a ferroelectric top layer to induce nonvolatile modulation of the conduction characteristic of monolayer MoS2 between a transistor and a junction state. In the presence of a domain wall, MoS2 exhibits rectified I-V characteristics that are well described by the thermionic emission model. The induced Schottky barrier height ΦeffB varies from 0.38 to 0.57 eV and is tunable by a SiO2 global back gate, while the tuning range of ΦeffB depends sensitively on the conduction-band-tail trapping states. Our work points to a new route to achieving programmable functionalities in van der Waals materials and sheds light on the critical performance limiting factors in these hybrid systems

Integrated Territorial and Urban Strategies - How are ESIF Adding Value in 2014-2020? : Final Report

The 2014-2020 regulatory provisions to EU Cohesion policy gave Member States new opportunities to use ESIF for sustainable urban development and other territorial strategies, particularly using Integrated Territorial Investment. This study examines how Member States are responding to these new provisions and how Cohesion policy is ‘adding value’ to regional, urban and local development. The study shows that there has been significant uptake of territorial strategies in 2014-2020, mainly in the form of sustainable urban development, across most Member States. Many of the strategies are new; the territorial provisions have encouraged innovation and adaptation in both thinking and practice. This innovation includes a more integrated approach to intervention, the implementation of strategies at different spatial scales, and more collaborative models of governance. There is scope for extending the use of territorial strategies in future, albeit with simplification of some of the regulatory requirements and more flexibility in programming. There is a need for institutional capacity-building to ensure efficient implementation at local level and greater emphasis on citizen engagement. Lastly, more attention needs to be given to monitoring and evaluating the outcomes of strategies

Simple ammonium salts acting on sigma-1 receptors yield potential treatments for cancer and depression

Sigma-1 and sigma-2 receptors are emerging therapeutic targets. We have identified that simple ammonium salts bind to these receptors and are effective in vivo. Radioligand binding assays were used to obtain structure-activity relationships of these salts. MTS assays were performed to determine their effect on growth in MCF7 and MDA-MB-486 cells. Anticancer properties were tested in NMRI mice transplanted with a fragment of mouse adenocarcinoma (MAC13). Antidepressant activity was tested using the forced-swim test and tailsuspension tests. Dipentylammonium (Ki 43 nM),tripentylammonium (Ki 15 nM) and trihexylammonium (Ki 9 nM) showed high affinity for the sigma-1receptor. Dioctanoylammonium had the highest affinity (K50 0.05 nM); this also showed the highest affinity for sigma-2 receptors (Ki 13 nM). Dipentylammonium was found to have antidepressant activity in vivo. Branched-chain ammonium salts showed lower affinity. Bis(2-ethylhexyl)ammonium (K50 29 μM), triisopentylammonium (K50 196 μM) and dioctanoylammonium showed a low Hill slope,and fitted a 2-site binding model for the sigma-1 receptor. We propose this two-site binding can be used to biochemically define a sigma-1 receptor antagonist. Bis(2-ethylhexyl)ammonium and triisopentylammonium were able to inhibit the growth of tumours in vivo. Cheap, simple ammonium salts act as sigma-1 receptor agonists and antagonists in vivo and require further investigation

Gefitinib and <i>EGFR</i> Gene Copy Number Aberrations in Esophageal Cancer

Purpose: The cancer esophagus gefitinib (COG) trial demonstrated improved progression free survival with the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib relative to placebo in advanced esophageal cancer patients with disease progression after chemotherapy. Rapid and durable responses were observed in a minority. We hypothesised that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Patients and Methods: A pre-specified blinded molecular analysis of COG trial tumours was conducted to compare efficacy of gefitinib to placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF and PIK3CA mutation status. EGFR CNG was determined by fluorescent insitu hybridisation (FISH) using pre-specified criteria and EGFR FISH positive defined as high polysomy or amplification. Results: Biomarker data were available for 340 patients. In EGFR FISH positive tumours (20.2%) overall survival was improved with gefitinib compared to placebo (hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.35, 1.00 p=0.05). In EGFR FISH negative tumours there was no difference in overall survival with gefitinib compared to placebo (HR for death, 0.90, 95% CI 0.69, 1.18 p=0.46). EGFR amplification (7.2%) patients gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI 0.07-0.64; p=0.006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF and PIK3CA mutations, or for any mutation versus none. Conclusion: EGFR CNG assessed by FISH appears to identify a subgroup of esophageal cancer patients who may benefit from gefitinib as a second line treatment, and suggests that anti-EGFR 3 therapies should be investigated in prospective clinical trials in different settings in EGFR FI SH positive, and in particular EGFR amplified, esophageal cancer

Frontiers, Opportunities, and Challenges in Biochemical and Chemical Catalysis of CO_2 Fixation

Two major energy-related problems confront the world in the next 50 years. First, increased worldwide competition for gradually depleting fossil fuel reserves (derived from past photosynthesis) will lead to higher costs, both monetarily and politically. Second, atmospheric CO_2 levels are at their highest recorded level since records began. Further increases are predicted to produce large and uncontrollable impacts on the world climate. These projected impacts extend beyond climate to ocean acidification, because the ocean is a major sink for atmospheric CO2.1 Providing a future energy supply that is secure and CO_2-neutral will require switching to nonfossil energy sources such as wind, solar, nuclear, and geothermal energy and developing methods for transforming the energy produced by these new sources into forms that can be stored, transported, and used upon demand