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As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.
To explore CRP in MDD and its phenotypic associations.
We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.
Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.
CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.
Declaration of interest
S.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.
Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.
To determine the impact of an environmental disinfection intervention on the incidence of healthcare-associated Clostridium difficile infection (CDI).
A multicenter randomized trial.
In total,16 acute-care hospitals in northeastern Ohio participated in the study.
We conducted a 12-month randomized trial to compare standard cleaning to enhanced cleaning that included monitoring of environmental services (EVS) personnel performance with feedback to EVS and infection control staff. We assessed the thoroughness of cleaning based on fluorescent marker removal from high-touch surfaces and the effectiveness of disinfection based on environmental cultures for C. difficile. A linear mixed model was used to compare CDI rates in the intervention and postintervention periods for control and intervention hospitals. The primary outcome was the incidence of healthcare-associated CDI.
Overall, 7 intervention hospitals and 8 control hospitals completed the study. The intervention resulted in significantly increased fluorescent marker removal in CDI and non-CDI rooms and decreased recovery of C. difficile from high-touch surfaces in CDI rooms. However, no reduction was observed in the incidence of healthcare-associated CDI in the intervention hospitals during the intervention and postintervention periods. Moreover, there was no correlation between the percentage of positive cultures after cleaning of CDI or non-CDI rooms and the incidence of healthcare-associated CDI.
An environmental disinfection intervention improved the thoroughness and effectiveness of cleaning but did not reduce the incidence of healthcare-associated CDI. Thus, interventions that focus only on improving cleaning may not be sufficient to control healthcare-associated CDI.
The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.
Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013–2014 influenza season. Little is known about the epidemiology of severe influenza during this season.
A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.
A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4–6.9], P=.006 and 50–64 years, 2.5 [1.3–4.9], P=.007; reference age 18–49 years), male sex (1.9 [1.1–3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9–37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2–1.4], P<.001).
Risk factors for death among US patients with severe influenza during the 2013–2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.
Infect. Control Hosp. Epidemiol. 2015;36(11):1251–1260
Silicon carbide power devices are purported to be capable of operating at very high temperatures. Current commercially available SiC MOSFETs from a number of manufacturers have been evaluated to understand and quantify the aging processes and temperature dependencies that occur when operated up to 350°C. High temperature constant positive bias stress tests demonstrated a two times increase in threshold voltage from the original value for some device types, which was maintained indefinitely but could be corrected with a long negative gate bias. The threshold voltages were found to decrease close to zero and the on-state resistances increased quite linearly to approximately five or six times their room temperature values. Long term thermal aging of the dies appears to demonstrate possible degradation of the ohmic contacts. This appears as a rectifying response in the I-V curves at low drain-source bias. The high temperature capability of the latest generations of these devices has been proven independently; provided that threshold voltage management is implemented, the devices are capable of being operated and are free from the effects of thermal aging for at least 70 hours cumulative at 300°C.
In this paper, high temperature (>1400°C) thermal oxidation has been applied, for the first time, to 4H-SiC PiN diodes with thick (110 μm) drift regions, for the purpose of increasing the carrier lifetime in the semiconductor. PiN diodes were fabricated using 4H-SiC material that had undergone thermal oxidation performed at 1400°C, 1500°C and 1600°C, then were electrically characterized. Forward current-voltage (I-V) measurements showed that thermally oxidized PiN diodes exhibited considerably improved electrical characteristics, with devices oxidized at 1500°C having a forward voltage drop (VF) of 4.15 V and a differential on-resistance (Ron,diff) of 8.9 mΩ-cm2 at 100 A/cm2 and 25°C. Compared to typical control sample PiN diode characteristics, this equated to an improvement of 8% and 23% for VF and Ron,diff, respectively. From analysis of the reverse recovery characteristics, the carrier lifetime of the PiN diodes oxidized at 1500°C was found to be 1.05 μs, which was an improvement of around 30% compared to the control sample PiN diodes.
Although 3C-SiC has a narrower bandgap than 4H-SiC, it is the only SiC polytype that can be grown directly over large area silicon substrates. It has the potential to provide a more economical choice than 4H-SiC for intermediate power devices, such as inverters for electric vehicles. To fabricate a vertical device on 3C-SiC, the Si substrate is usually removed either by etching or polishing. Neither of these processes is economical nor efficient. In this paper we propose a lateral Schottky diode design for 3C-SiC on Si structure. 2D finite element simulations using ATLAS showed that a breakdown voltage beyond 1200 V can be achieved with a 4 μm thick epilayer. Physical models used for 3C-SiC/Si power devices simulations are introduced. Advantages of lateral 3C-SiC/Si diodes over free standing 3C-SiC are also discussed.