Carbon-related defects in Si:C/silicon heterostructures assessed by deep-level transient spectroscopy

This paper reports on a Deep-Level Transient Spectroscopy (DLTS) study of the electrically active defects in similar to 100 nm Si: C stressors, formed by chemical vapor deposition on p-type Czochralski silicon substrates. In addition, the impact of a post-deposition Rapid Thermal Annealing (RTA) at 850 degrees C on the DLT-spectra is investigated. It is shown that close to the surface at least two types of hole traps are present: one kind exhibiting slow hole capture, which may have a partial extended defect nature and a second type of hole trap behaving like a point defect. RTA increases the concentration of both hole traps and, in addition, introduces a point defect at EV + 0.35 eV in the depletion region of the silicon substrate at some distance from the Si: C epi layer. This level most likely corresponds with CiOi-related centers. Finally, a negative feature is found systematically for larger reverse bias pulses, which could point to a response of trap states at the Si: C/silicon hetero-interface

Treatment biomarkers for ADHD: Taking stock and moving forward

The development of treatment biomarkers for psychiatric disorders has been challenging, particularly for heterogeneous neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD). Promising findings are also rarely translated into clinical practice, especially with regard to treatment decisions and development of novel treatments. Despite this slow progress, the available neuroimaging, electrophysiological (EEG) and genetic literature provides a solid foundation for biomarker discovery. This article gives an updated review of promising treatment biomarkers for ADHD which may enhance personalized medicine and novel treatment development. The available literature points to promising pre-treatment profiles predicting efficacy of various pharmacological and non-pharmacological treatments for ADHD. These candidate predictive biomarkers, particularly those based on low-cost and non-invasive EEG assessments, show promise for the future stratification of patients to specific treatments. Studies with repeated biomarker assessments further show that different treatments produce distinct changes in brain profiles, which track treatment-related clinical improvements. These candidate monitoring/response biomarkers may aid future monitoring of treatment effects and point to mechanistic targets for novel treatments, such as neurotherapies. Nevertheless, existing research does not support any immediate clinical applications of treatment biomarkers for ADHD. Key barriers are the paucity of replications and external validations, the use of small and homogeneous samples of predominantly White children, and practical limitations, including the cost and technical requirements of biomarker assessments and their unknown feasibility and acceptability for people with ADHD. We conclude with a discussion of future directions and methodological changes to promote clinical translation and enhance personalized treatment decisions for diverse groups of individuals with ADHD

Study of electrically active defects in epitaxial layers on silicon

Electrically active defects in silicon-based epitaxial layers on silicon substrates have been studied by Deep-Level Transient Spectroscopy (DLTS). Several aspects have been investigated, like, the impact of the pre-epi cleaning conditions and the effect of a post-deposition anneal on the deep-level properties. It is shown that the pre-cleaning thermal budget has a strong influence on the defects at the substrate/epi layer interface. At the same time, a post-deposition Forming Gas Anneal can passivate to a large extent the active defect states. Finally, it is shown that application of a post-deposition anneal increases the out-diffusion of carbon from a Si:C stressor layer into the p-type CZ substrate

Alpha Event-Related Decreases During Encoding in Adults with ADHD - An Investigation of Sustained Attention and Working Memory Processes.

BACKGROUND: Executive functioning deficits are central to established neuropsychological models of ADHD. Oscillatory activity, particularly the alpha rhythm (8-12Hz) has been associated with cognitive impairments in ADHD. However, most studies to date examined such neural mechanisms underlying executive dysfunction in children and adolescents with ADHD, raising the question of whether and to what extent those ADHD-related working memory impairments are still present in adults. To this end, the current study aimed to investigate the role of alpha event-related decreases (ERD) during working memory processes in adults with and without ADHD. METHODS: We collected electroencephalographic (EEG) data from 85 adults with a lifetime diagnosis of ADHD and 105 controls (aged 32-64), while they performed a continuous performance (CPT) and a Sternberg working memory task (SDRT). Time-frequency and independent component analysis (ICA) was used to identify alpha (8-12Hz) clusters to examine group and condition effects during the temporal profile of sustained attention and working memory processes (encoding, maintenance, retrieval), loads (low and high) and trial type (go and nogo). RESULTS: Individuals with ADHD exhibited higher reaction time-variability in SDRT, and slower response times in SDRT and CPT, despite no differences in task accuracy. Although working memory load was associated with stronger alpha ERD in both tasks and both groups (ADHD, controls), we found no evidence for attenuated alpha ERD in adults with ADHD, failing to replicate effects reported in children. In contrast, when looking at the whole sample, the correlations of alpha power during encoding with inattention and hyperactivity-impulsivity symptoms were significant, replicating prior findings in children with ADHD, but suggesting an alternate source for these effects in adults. CONCLUSIONS: Our results corroborate the robustness of alpha as a marker of visual attention and suggest that occipital alpha ERD normalizes in adulthood, but with unique contributions of centro-occipital alpha ERD, suggesting a secondary source. This implies that deviations in processes other than previously reported visuospatial cortex engagement account for the persistent symptoms and cognitive deficits in adults with a history of ADHD

Atypical functional connectivity in adolescents and adults with persistent and remitted ADHD during a cognitive control task

Abstract We previously provided initial evidence for cognitive and event-related potential markers of persistence/remission of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and adulthood. Here, using a novel brain-network connectivity approach, we aimed to examine whether task-based functional connectivity reflects a marker of ADHD remission or an enduring deficit unrelated to ADHD outcome. High-density EEG was recorded in a follow-up of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 typically developing individuals during an arrow-flanker task, eliciting cognitive control. Functional connectivity was quantified with network-based graph-theory metrics before incongruent (high-conflict) target onset (pre-stimulus), during target processing (post-stimulus) and in the degree of change between pre-stimulus/post-stimulus. ADHD outcome was examined with parent-reported symptoms and impairment using both a categorical (DSM-IV) and a dimensional approach. Graph-theory measures converged in indicating that, compared to controls, ADHD persisters showed increased connectivity in pre-stimulus theta, alpha, and beta and in post-stimulus beta (all p < .01) and reduced pre-stimulus/post-stimulus change in theta connectivity (p < .01). In the majority of indices showing ADHD persister–control differences, ADHD remitters differed from controls (all p < .05) but not from persisters. Similarly, connectivity measures were unrelated to continuous outcome measures of ADHD symptoms and impairment in participants with childhood ADHD. These findings indicate that adolescents and young adults with persistent and remitted ADHD share atypical over-connectivity profiles and reduced ability to modulate connectivity patterns with task demands, compared to controls. Task-based functional connectivity impairments may represent enduring deficits in individuals with childhood ADHD irrespective of diagnostic status in adolescence/young adulthood

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BackgroundExisting evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.Patients and methodsChemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.ResultsNinety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).ConclusionsWhile elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes

Pathology and behaviour in feline medicine: investigating the link between vomeronasalitis and aggression

Objectives The aim of the study was to investigate if the feline vomeronasal organ (VNO) can be affected by inflammatory lesions and if these changes are associated with behavioural alterations. Methods VNOs from 20 cats were sampled during necropsy, submitted for routine tissue processing and stained with haematoxylin and eosin for histopathological evaluation. Of the 20 cats, data on the presence of aggressive behaviours towards cats or humans were collected by questionnaire survey at the point of death. Inflammatory lesions were classified depending on the duration of the process as acute or chronic, both in vomeronasal sensory epithelium (VNSE) and in non-sensory epithelium (NSE). Fisher’s exact test was used to compare VNO inflammation with behavioural data. Results The VNSE was inflamed in 11/20 VNOs (55%) while the NSE was inflamed in 13/20 (65%). Overall, the VNO was affected by inflammation in 14/20 (70%) cats, and all the lesions were classified as chronic. Five out of 20 cats (25%) had documented intraspecific aggressive behaviours and 8/20 (40%) had shown aggression towards humans. Fisher’s exact test showed a statistically significant correlation between inflammation of the VNSE and intraspecific aggression (P = 0.038). No statistically correlations were observed between VNSE inflammation and aggression towards humans and between NSE inflammation and aggression towards cats or humans. Conclusions and relevance Our results show, for the first time, the existence of vomeronasalitis in animals and its possible association with intraspecific aggressive behaviours. The inflammatory microenvironment could impair VNSE functionality, causing intraspecific communication alterations, probably through a reduction in chemical communication action and perception. Owing to the pivotal role of the VNO in the social life of cats and other species, this report provides a rationale to further investigate this disease in relation to a variety of behavioural disorders

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Protein Conformation and Supercharging with DMSO from Aqueous Solution

The efficacy of dimethyl sulfoxide (DMSO) as a supercharging reagent for protein ions formed by electrospray ionization from aqueous solution and the mechanism for supercharging were investigated. Addition of small amounts of DMSO to aqueous solutions containing hen egg white lysozyme or equine myoglobin results in a lowering of charge, whereas a significant increase in charge occurs at higher concentrations. Results from both near-UV circular dichroism spectroscopy and solution-phase hydrogen/deuterium exchange mass spectrometry indicate that DMSO causes a compaction of the native structure of these proteins at low concentration, but significant unfolding occurs at ~63% and ~43% DMSO for lysozyme and myoglobin, respectively. The DMSO concentrations required to denature these two proteins in bulk solution are ~3–5 times higher than the concentrations required for the onset of supercharging, consistent with a significantly increased concentration of this high boiling point supercharging reagent in the ESI droplet as preferential evaporation of water occurs. DMSO is slightly more basic than m-nitrobenzyl alcohol and sulfolane, two other supercharging reagents, based on calculated proton affinity and gas-phase basicity values both at the B3LYP and MP2 levels of theory, and all three of these supercharging reagents are significantly more basic than water. These results provide additional evidence that the origin of supercharging from aqueous solution is the result of chemical and/or thermal denaturation that occurs in the ESI droplet as the concentration of these supercharging reagents increases, and that proton transfer reactivity does not play a significant role in the charge enhancement observed

Probing the quantum vacuum with an artificial atom in front of a mirror

Quantum fluctuations of the vacuum are both a surprising and fundamental phenomenon of nature. Understood as virtual photons flitting in and out of existence, they still have a very real impact, \emph{e.g.}, in the Casimir effects and the lifetimes of atoms. Engineering vacuum fluctuations is therefore becoming increasingly important to emerging technologies. Here, we shape vacuum fluctuations using a "mirror", creating regions in space where they are suppressed. As we then effectively move an artificial atom in and out of these regions, measuring the atomic lifetime tells us the strength of the fluctuations. The weakest fluctuation strength we observe is 0.02 quanta, a factor of 50 below what would be expected without the mirror, demonstrating that we can hide the atom from the vacuum