"Give me some space" : exploring youth to parent aggression and violence

A small scale qualitative project, undertaken by an interdisciplinary domestic violence research group involving academic researchers and research assistants, with colleagues from Independent Domestic Abuse Services (IDAS), investigated youth aggression and violence against parents. Following the literature review, data was generated through several research conversations with young people (n = 2), through semi-structured interviews with mothers (n = 3) and practitioners (n = 5), and through a practitioner focus group (n = 8). Thematic analysis and triangulation of the data from parents, practitioners and young people, elicited interconnected and complex overarching themes. Young people could be both victim and perpetrator. The witnessing or experiencing of domestic aggression and violence raised the concept of ‘bystander children’. The impact of young people experiencing familial violence was underestimated by parents. For practitioners, the effects of working with domestic violence was shown to be significant - both positively and negatively

Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis

Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non–cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte–mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity

Understanding within-session loss-chasing: an experimental investigation of the impact of stake size on cognitive control

Loss-chasing is a central feature of problematic gambling, yet it remains a poorly conceived and understood concept. Loss-chasing is believed to stem from an ero- sion of cognitive control when gambling. The opportunity to gamble at significantly dis- parate stake sizes on a gambling activity is considered to be a risk factor for loss-chasing. This study investigated the impact of gambling at disparate stake sizes on executive processes integral to maintaining cognitive control when gambling, namely response inhibition and reflection impulsivity. Frequent adult non-problem gamblers (n = 32) participated in a repeated measures experiment; and gambled at three disparate stake sizes (£20, £2 and no stake per bet) on a simulated gambling task. Participants’ response inhibition performance and reflection impulsivity levels after gambling at various stake sizes were compared via a go/no-go task and information sampling task, respectively. Quality of decision-making i.e. the evaluation of available information to make probability judgements was impaired after gambling at higher stakes in comparison to lower stakes, indicating an increase in reflection impulsivity. No effect on response inhibition was observed. Although exploratory, this suggests that the opportunity for participants to substantially increase stake size on a gambling activity may be a risk factor for impaired cognitive performance when gambling, and perhaps create vulnerability for within-session loss-chasing in some players. Keywords Problem gambling - Cognitive control - Loss-chasing - Response inhibition - Reflection impulsivit

Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers

Pathological gambling (PG) is associated with maladaptive perseverative behavior, but the underlying mechanism and neural circuitry is not completely clear. Here, the hypothesis was tested that PG is characterized by response perseveration and abnormalities in reward and/or punishment sensitivity in the ventral frontostriatal circuit. Executive functioning was assessed to verify if these effects are independent of the dorsal frontostriatal circuit. A group of smokers was also included to examine whether impairments in PG generalize to substance use disorders. Response perseveration and reward/punishment sensitivity were measured with a probabilistic reversal-learning task, in which subjects could win and lose money. Executive functioning was measured with a planning task, the Tower of London. Performance and fMRI data were acquired in 19 problem gamblers, 19 smokers, and 19 healthy controls. Problem gamblers showed severe response perseveration, associated with reduced activation of right ventrolateral prefrontal cortex in response to both monetary gain and loss. Results did not fully generalize to smokers. Planning performance and related activation of the dorsal frontostriatal circuit were intact in both problem gamblers and smokers. PG is related to response perseveration and diminished reward and punishment sensitivity as indicated by hypoactivation of the ventrolateral prefrontal cortex when money is gained and lost. Moreover, intact planning abilities and normal dorsal frontostriatal responsiveness indicate that this deficit is not due to impaired executive functioning. Response perseveration and ventral prefrontal hyporesponsiveness to monetary loss may be markers for maladaptive behavior seen in chemical and nonchemical addictions. © 2009 Nature Publishing Group All rights reserved

Nanosize Titanium Dioxide Stimulates Reactive Oxygen Species in Brain Microglia and Damages Neurons in Vitro

BackgroundTitanium dioxide is a widely used nanomaterial whose photo-reactivity suggests that it could damage biological targets (e.g., brain) through oxidative stress (OS).ObjectivesBrain cultures of immortalized mouse microglia (BV2), rat dopaminergic (DA) neurons (N27), and primary cultures of embryonic rat striatum, were exposed to Degussa P25, a commercially available TiO2 nanomaterial. Physical properties of P25 were measured under conditions that paralleled biological measures.FindingsP25 rapidly aggregated in physiological buffer (800–1,900 nm; 25°C) and exposure media (~ 330 nm; 37°C), and maintained a negative zeta potential in both buffer (–12.2 ± 1.6 mV) and media (–9.1 ± 1.2 mV). BV2 microglia exposed to P25 (2.5–120 ppm) responded with an immediate and prolonged release of reactive oxygen species (ROS). Hoechst nuclear stain was reduced after 24-hr (≥100 ppm) and 48-hr (≥2.5 ppm) exposure. Microarray analysis on P25-exposed BV2 microglia indicated up-regulation of inflammatory, apoptotic, and cell cycling pathways and down-regulation of energy metabolism. P25 (2.5–120 ppm) stimulated increases of intracellular ATP and caspase 3/7 activity in isolated N27 neurons (24–48 hr) but did not produce cytotoxicity after 72-hr exposure. Primary cultures of rat striatum exposed to P25 (5 ppm) showed a reduction of immunohistochemically stained neurons and microscopic evidence of neuronal apoptosis after 6-hr exposure. These findings indicate that P25 stimulates ROS in BV2 microglia and is nontoxic to isolated N27 neurons. However, P25 rapidly damages neurons at low concentrations in complex brain cultures, plausibly though microglial generated ROS

Diagnosing acute coronary syndrome in telephone triage: does it matter who initially calls? A cross-sectional study

BACKGROUND: Adequate triage of patients with symptoms suggestive of ACS is crucial. Considering who calls might be useful to improve telephone triage of these patients. In this article, we aim to assess whether a call made by a surrogate is related to urgency allocation or higher odds of an acute coronary syndrome (ACS) than patient-initiated calls, and to assess possible gender differences. METHODS: Cross-sectional study of patients with symptoms suggestive of ACS who called the out-of-hours service in primary care (OHS-PC). Calls were classified into "patient-initiated call" or "surrogate call". Call and patient characteristics were collected. Odds ratios (OR) were calculated for the relationship between the type of call and (i) urgency allocation, (ii) ACS, and (iii) ACS or other life-threatening event, stratified for gender. RESULTS: In total 2,428 recordings were included for analysis. Around half of the recordings were surrogate calls, and these more often received a high urgency (80.0%) than patient-initiated calls (57.8%), OR 2.92 (95%CI 2.44-3.50); in women OR 3.46, (95%CI 2.70-4.45), in men OR 2.42 (95%CI 1.86-3.16). Of all participants, 11.0% were diagnosed with an ACS; in women 8.0%, in men 14.7%. In the surrogate call group this was 14.4%, in the patient-initiated call group 7.6%; OR 2.04 (95%CI 1.57-2.67). In women, the OR was 2.46 (95%CI 1.63-3.77), in men 1.69 (95%CI 1.20-2.41). CONCLUSIONS: Compared to patients who call themselves, surrogate calls on behalf of a patient with symptoms suggestive of ACS receive more often a high urgency, and these patients have a risk twice as high of an ACS, an effect similar in women and men. It is useful for triage at the OHS-PC to consider who calls if it concerns a patient with symptoms suggestive of ACS. CLINICAL TRIAL NUMBER: NTR7331. Registration Date 26-06-2018

Optical switching of nuclear spin–spin couplings in semiconductors

Two-qubit operation is an essential part of quantum computation. However, solid-state nuclear magnetic resonance quantum computing has not been able to fully implement this functionality, because it requires a switchable inter-qubit coupling that controls the time evolutions of entanglements. Nuclear dipolar coupling is beneficial in that it is present whenever nuclear–spin qubits are close to each other, while it complicates two-qubit operation because the qubits must remain decoupled to prevent unwanted couplings. Here we introduce optically controllable internuclear coupling in semiconductors. The coupling strength can be adjusted externally through light power and even allows on/off switching. This feature provides a simple way of switching inter-qubit couplings in semiconductor-based quantum computers. In addition, its long reach compared with nuclear dipolar couplings allows a variety of options for arranging qubits, as they need not be next to each other to secure couplings

Impaired Inhibitory Control in Recreational Cocaine Users

Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed

Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency

BACKGROUND:Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been shown capable of reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4; however it has been unknown whether this same strategy could apply to human NSCs, which would result in more relevant pluripotent stem cells for modeling human disease. METHODOLOGY AND PRINCIPAL FINDINGS:Here, we show that OCT3/4 and KLF4 are indeed sufficient to induce pluripotency from human NSCs within a two week time frame and are molecularly indistinguishable from human ES cells. Furthermore, human NSC-derived pluripotent stem cells can differentiate into all three germ lineages both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE:We propose that human NSCs represent an attractive source of cells for producing human iPS cells since they only require two factors, obviating the need for c-MYC, for induction into pluripotency. Thus, in vitro human disease models could be generated from iPS cells derived from human NSCs