Enhancement-mode PEDOT:PSS organic electrochemical transistors using molecular de-doping

Organic electrochemical transistors (OECTs) show great promise for flexible, low-cost, and low-voltage sensors for aqueous solutions. The majority of OECT devices are made using the polymer blend poly(ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), in which PEDOT is intrinsically doped due to inclusion of PSS. Because of this intrinsic doping, PEDOT:PSS OECTs generally operate in depletion mode, which results in a higher power consumption and limits stability. Here, a straightforward method to de-dope PEDOT:PSS using commercially available amine-based molecular de-dopants to achieve stable enhancement-mode OECTs is presented. The enhancement-mode OECTs show mobilities near that of pristine PEDOT:PSS (≈2 cm2 V−1 s−1) with stable operation over 1000 on/off cycles. The electron and proton exchange among PEDOT, PSS, and the molecular de-dopants are characterized to reveal the underlying chemical mechanism of the threshold voltage shift to negative voltages. Finally, the effect of the de-doping on the microstructure of the spin-cast PEDOT:PSS films is investigated.</p

On the link between ocean biota emissions, aerosol, and maritime clouds: Airborne, ground, and satellite measurements off the coast of California

Surface, airborne, and satellite measurements over the eastern Pacific Ocean off the coast of California during the period between 2005 and 2007 are used to explore the relationship between ocean chlorophyll a, aerosol, and marine clouds. Periods of enhanced chlorophyll a and wind speed are coincident with increases in particulate diethylamine and methanesulfonate concentrations. The measurements indicate that amines are a source of secondary organic aerosol in the marine atmosphere. Subsaturated aerosol hygroscopic growth measurements indicate that the organic component during periods of high chlorophyll a and wind speed exhibit considerable water uptake ability. Increased average cloud condensation nucleus (CCN) activity during periods of increased chlorophyll a levels likely results from both size distribution and aerosol composition changes. The available data over the period of measurements indicate that the cloud microphysical response, as represented by either cloud droplet number concentration or cloud droplet effective radius, is likely influenced by a combination of atmospheric dynamics and aerosol perturbations during periods of high chlorophyll a concentrations

2022 roadmap on neuromorphic computing and engineering

Modern computation based on von Neumann architecture is now a mature cutting-edge science. In the von Neumann architecture, processing and memory units are implemented as separate blocks interchanging data intensively and continuously. This data transfer is responsible for a large part of the power consumption. The next generation computer technology is expected to solve problems at the exascale with 10$^{18}$ calculations each second. Even though these future computers will be incredibly powerful, if they are based on von Neumann type architectures, they will consume between 20 and 30 megawatts of power and will not have intrinsic physically built-in capabilities to learn or deal with complex data as our brain does. These needs can be addressed by neuromorphic computing systems which are inspired by the biological concepts of the human brain. This new generation of computers has the potential to be used for the storage and processing of large amounts of digital information with much lower power consumption than conventional processors. Among their potential future applications, an important niche is moving the control from data centers to edge devices. The aim of this roadmap is to present a snapshot of the present state of neuromorphic technology and provide an opinion on the challenges and opportunities that the future holds in the major areas of neuromorphic technology, namely materials, devices, neuromorphic circuits, neuromorphic algorithms, applications, and ethics. The roadmap is a collection of perspectives where leading researchers in the neuromorphic community provide their own view about the current state and the future challenges for each research area. We hope that this roadmap will be a useful resource by providing a concise yet comprehensive introduction to readers outside this field, for those who are just entering the field, as well as providing future perspectives for those who are well established in the neuromorphic computing community

The prevalence, correlation, and co-occurrence of neuropathology in old age: harmonisation of 12 measures across six community-based autopsy studies of dementia

Background: Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population. Methods: We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies. Findings: The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0–91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20–0·42]). Interpretation: Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted. Funding: Gates Ventures

Preoperative information for ICU patients to reduce anxiety during and after the ICU-stay: protocol of a randomized controlled trial [NCT00151554]

BACKGROUND: According to current evidence and psychological theorizing proper information giving seems to be a promising way to reduce patient anxiety. In the case of surgical patients, admission to the intensive care unit (ICU) is strongly associated with uncertainty, unpredictability and anxiety for the patient. Thus, ICU specific information could have a high clinical impact. This study investigates the potential benefits of a specifically designed ICU-related information program for patients who undergo elective cardiac, abdominal or thoracic surgery and are scheduled for ICU stay. METHODS/DESIGN: The trial is designed as a prospective randomized controlled trial including an intervention and a control group. The control group receives the standard preparation currently conducted by surgeons and anesthetists. The intervention group additionally receives a standardized information program with specific procedural, sensory and coping information about the ICU. A measurable clinical relevant difference regarding anxiety will be expected after discharge from ICU. Power calculation (α = 0.05; β = 0.20; Δ = 8.50 score points) resulted in a required sample size of N = 120 cardiac surgical patients (n = 60 vs. n = 60). Furthermore, N = 20 abdominal or thoracic surgical patients will be recruited (n = 10 vs. n = 10) to gain insight to a possible generalization to other patient groups. Additionally the moderating effect of specific patient attributes (need for cognition, high trait anxiety) will be investigated to identify certain patient groups which benefit most. DISCUSSION: The proposed study promises to strengthen evidence on effects of a specific, concise information program that addresses the information needs of patients scheduled for ICU stay

Re-Patterning Sleep Architecture in Drosophila through Gustatory Perception and Nutritional Quality

Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary factors and sleep behavior in Drosophila melanogaster. Dietary sugar rapidly altered sleep behavior by modulating the number of sleep episodes during both the light and dark phase of the circadian period, independent of an intact circadian rhythm and without affecting total sleep, latency to sleep, or waking activity. The effect of sugar on sleep episode number was consistent with a change in arousal threshold for waking. Dietary protein had no significant effect on sleep or wakefulness. Gustatory perception of sugar was necessary and sufficient to increase the number of sleep episodes, and this effect was blocked by activation of bitter-sensing neurons. Further addition of sugar to the diet blocked the effects of sweet gustatory perception through a gustatory-independent mechanism. However, gustatory perception was not required for diet-induced fat accumulation, indicating that sleep and energy storage are mechanistically separable. We propose a two-component model where gustatory and metabolic cues interact to regulate sleep architecture in response to the quantity of sugar available from dietary sources. Reduced arousal threshold in response to low dietary availability may have evolved to provide increased responsiveness to cues associated with alternative nutrient-dense feeding sites. These results provide evidence that gustatory perception can alter arousal thresholds for sleep behavior in response to dietary cues and provide a mechanism by which organisms tune their behavior and physiology to environmental cues

The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth

Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeleto ns. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology

IL-2 Mediates CD4+ T Cell Help in the Breakdown of Memory-Like CD8+ T Cell Tolerance under Lymphopenic Conditions

Background: Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8 + T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4 + T helper cells. Methodology/Principal Findings: Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8 + and CD4 + T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8 + T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8 + T cell self-reactivity. Conclusions/Significance: IL-2 mediates the cooperation of memory-like CD4 + and CD8 + T cells in the breakdown of crosstolerance, resulting in effector cytotoxic T lymphocyte differentiation and the induction of autoimmune disease

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme