Total Cerebral Small Vessel Disease MRI Score Is Associated with Cognitive Decline in Executive Function in Patients with Hypertension

Objectives: Hypertension is a major risk factor for white matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces, which are MRI markers of cerebral small vessel disease (SVD). Studies have shown associations between these individual MRI markers and cognitive functioning and decline. Recently, a “total SVD score” was proposed in which the different MRI markers were combined into one measure of SVD, to capture total SVD-related brain damage. We investigated if this SVD score was associated with cognitive decline over 4 years in patients with hypertension. Methods: In this longitudinal cohort study, 130 hypertensive patients (91 patients with uncomplicated hypertension and 39 hypertensive patients with a lacunar stroke) were included. They underwent a neuropsychological assessment at baseline and after 4 years. The presence of WMH, lacunes, cerebral microbleeds, and perivascular spaces were rated on baseline MRI. Presence of each individual marker was added to calculate the total SVD score (range 0–4) in each patient. Results: Uncorrected linear regression analyses showed associations between SVD score and decline in overall cognition (p = 0.017), executive functioning (p < 0.001) and information processing speed (p = 0.037), but not with memory (p = 0.911). The association between SVD score and decline in overall cognition and executive function remained significant after adjustment for age, sex, education, anxiety and depression score, potential vascular risk factors, patient group, and baseline cognitive performance. Conclusion: Our study shows that a total SVD score can predict cognitive decline, specifically in executive function, over 4 years in hypertensive patients. This emphasizes the importance of considering total brain damage due to SVD

Differential effects of inhibitors of the PI3K/mTOR pathway on the expansion and functionality of regulatory T cells

AbstractThe PI3K/mTOR pathway is commonly deregulated in cancer. mTOR inhibitors are registered for the treatment of several solid tumors and novel inhibitors are explored clinically. Notably, this pathway also plays an important role in immunoregulation. While mTOR inhibitors block cell cycle progression of conventional T cells (Tconv), they also result in the expansion of CD4+CD25hiFOXP3+ regulatory T cells (Tregs), and this likely limits their clinical antitumor efficacy. Here, we compared the effects of dual mTOR/PI3K inhibition (using BEZ235) to single PI3K (using BKM120) or mTOR inhibition (using rapamycin and everolimus) on Treg expansion and functionality. Whereas rapamycin, everolimus and BEZ235 effected a relative expansion benefit for Tregs and increased their overall suppressive activity, BKM120 allowed for similar expansion rates of Tregs and Tconv without altering their overall suppressive activity. Therefore, PI3K inhibition alone might offer antitumor efficacy without the detrimental selective expansion of Tregs associated with mTOR inhibition

Emotions, personality, and psychopathology of cybersecurity breach victims

The increasing adoption of IoT devices in households has the potential to make life easier and more convenient, but it also poses a greater challenge to system security since several IoT devices are not yet adequately protected against cybersecurity breaches. Understanding the psychological impact of cybersecurity breaches from the user’s perspective is relevant to improve the users’ safety and wellbeing when using devices connected to the Internet. The current study, part of a larger research project on the emotional impact of threats to cybersecurity, aims to identify interindividual differences in emotion processes that users experience in scenarios of a cybersecurity breach and anomalous behaviour of IoT devices installed in their homes. A total of 1000 participants from the United Kingdom and the Netherlands reported their emotion processes as a reaction to the cybersecurity breach scenarios involving the smart security camera, by indicating their reactions on the Cybersecurity GRID questionnaire, which consists of 73 items describing emotion processes in cybersecurity breach situations on a 7-point response scale. Additionally, the participants filled in questionnaires about psychopathology, resilience and personality. Principal component analysis applied on emotion process items revealed a three-component structure: GENERAL EMOTION INTENSITY, DO vs ATTACK/WITHDRAW and AFFECT VS APPRAISAL/ACTION TENDENCY. Results, interpretation and implications of inter-individual differences in emotional processes between ambiguous (unclear whether the IoT device malfunctioned or the third party took control) and unambiguous (evident that a third party took control) cybersecurity breach scenarios in relation to personality, depression, anxiety, aggression and resilience will be presented

Association of Vitamin B12 Deficiency with Fatigue and Depression after Lacunar Stroke

Background: In lacunar stroke patients vitamin B12 deficiency is often found and a relationship with the degree of periventricular white matter lesions (pWMLs) is suggested. Given the known relationships between WMLs and depression and between depression and fatigue after stroke, we studied both depression and fatigue in lacunar stroke patients with and without vitamin B12 deficiency. Methods: In 40 first-ever lacunar stroke patients vitamin B12 levels were determined and self-report questionnaires for fatigue and depression were completed three months after stroke. Results: Lacunar stroke patients with vitamin B12 deficiency (N = 13) reported significantly more fatigue (90.7 versus 59.4; p =.001) and depressive symptoms (6.62 versus 3.89; p,.05) than those without (N = 27). In regression analyses, vitamin B12 deficiency was significantly and independently associated with the presence of severe fatigue and clinically significant depression. Conclusions: Our preliminary results suggest a relationship between vitamin B12 deficiency and increased levels of fatigue and depression in lacunar stroke patients. If these findings could be replicated in a larger and general stroke sample, thi

Employment relations and dismissal regulations: does employment legislation protect the health of workers?

Sociologists have long acknowledged that being in a precarious labour market position, whether employed or unemployed, can harm peoples' health. However, scholars have yet to fully investigate the possible contextual, institutional determinants of this relationship. Two institutions that were overlooked in previous empirical studies are the regulations that set minimum compensation for dismissal, severance payments, and entitlements to a period of notice before dismissal, notice periods. These institutions may be important for workers' health as they influence the degree of insecurity that workers are exposed to. Here, we test this hypothesis by examining whether longer notice periods and greater severance payments protect the health of labour market participants, both employed and unemployed. We constructed two cohorts of panel data before and during the European recession using data from 22 countries in the European Union Statistics on Income and Living Conditions (person years = 338,000). We find more generous severance payments significantly reduce the probability that labour market participants, especially the unemployed, will experience declines in self-reported health, with a slightly weaker relationship for longer notice periods

Australians’ views on carbon pricing before and after the 2013 federal election

As climate policies change through the legislative process, public attitudes towards them may change as well. Therefore, it is important to assess how people accept and support controversial climate policies as the policies change over time. Policy acceptance is a positive evaluation of, or attitude towards, an existing policy; policy support adds an active behavioural component1, 3. Acceptance does not necessarily lead to support. We conducted a national survey of Australian residents to investigate acceptance of, and support for, the Australian carbon pricing policy before and after the 2013 federal election, and how perceptions of the policy, economic ideology, and voting behaviour affect acceptance and support. We found acceptance and support were stable across the election period, which was surprising given that climate policy was highly contentious during the election. Policy acceptance was higher than policy support at both times and acceptance was a necessary but insufficient condition of support. We conclude that acceptance is an important process through which perceptions of the policy and economic ideology influence support. Therefore, future climate policy research needs to distinguish between acceptance and support to better understand this process, and to better measure these concepts

Impact of small vessel disease in the brain on gait and balance

Gait and balance impairment is highly prevalent in older people. We aimed to assess whether and how single markers of small vessel disease (SVD) or a combination thereof explain gait and balance function in the elderly. We analysed 678 community-dwelling healthy subjects from the Lothian Birth Cohort 1936 at the age of 71–74 years who had undergone comprehensive risk factor assessment, gait and balance assessment as well as brain MRI. We investigated the impact of individual SVD markers (white matter hyperintensity – WMH, microbleeds, lacunes, enlarged perivascular spaces, brain atrophy) as seen on structural brain MRI and of a global SVD score on the patients’ performance. A regression model revealed that age, sex, and hypertension significantly explained gait speed. Among SVD markers white matter hyperintensity (WMH) score or volume were additional significant and independent predictors of gait speed in the regression model. A similar association was seen with the global SVD score. Our study confirms a negative impact of SVD-related morphologic brain changes on gait speed in addition to age, sex and hypertension independent from brain atrophy. The presence of WMH seems to be the major driving force for SVD on gait impairment in healthy elderly subjects

User experiences with simulated cyber‑physical attacks on smart home IoT

With the Internet of Things (IoT) becoming increasingly prevalent in people’s homes, new threats to residents are emerging such as the cyber-physical attack, i.e. a cyber-attack with physical consequences. In this study, we aimed to gain insights into how people experience and respond to cyber-physical attacks to their IoT devices. We conducted a naturalistic field experiment and provided 9 Dutch and 7 UK households, totalling 18 and 13 participants respectively, with a number of smart devices for use in their home. After a period of adaptation, simulated attacks were conducted, leading to events of varying noticeability (e.g., the light going on or off once or several times). After informing people simulated attacks had occurred, the attacks were repeated one more time. User experiences were collected through interviews and analysed with thematic analyses. Four relevant themes were identified, namely (1) the awareness of and concern about privacy and security risks was rather low, (2) the simulated attacks made little impression on the participants, (3) the participants had difficulties with correctly recognizing simulated attacks, and (4) when informed about simulated attacks taking place; participants noticed more simulated attacks and presented decision rules for them (but still were not able to identify and distinguish them well—see Theme 3). The findings emphasise the need for training interventions and an intrusion detection system to increase detection of cyber-physical attacks.European Union funding: G0H6416N-FWOOPR201600970; Engineering and Physical Sciences Research Council (EPSRC): EP/P016448/1; NWO: 651.002.00

Functional Analysis of a Breast Cancer-Associated FGFR2 Single Nucleotide Polymorphism Using Zinc Finger Mediated Genome Editing

The authors thank Barts Charity for funding and Breast Cancer Campaign for funding the Barts Breast Tissue Bank