One-by-one trap activation in silicon nanowire transistors

Flicker or 1/f noise in metal-oxide-semiconductor field-effect transistors (MOSFETs) has been identified as the main source of noise at low frequency. It often originates from an ensemble of a huge number of charges trapping and detrapping. However, a deviation from the well-known model of 1/f noise is observed for nanoscale MOSFETs and a new model is required. Here, we report the observation of one-by-one trap activation controlled by the gate voltage in a nanowire MOSFET and we propose a new low-frequency-noise theory for nanoscale FETs. We demonstrate that the Coulomb repulsion between electronically charged trap sites avoids the activation of several traps simultaneously. This effect induces a noise reduction by more than one order of magnitude. It decreases when increasing the electron density in the channel due to the electrical screening of traps. These findings are technologically useful for any FETs with a short and narrow channel.Comment: One file with paper and supplementary informatio

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Orthogonal Range Reporting and Rectangle Stabbing for Fat Rectangles

In this paper we study two geometric data structure problems in the special case when input objects or queries are fat rectangles. We show that in this case a significant improvement compared to the general case can be achieved. We describe data structures that answer two- and three-dimensional orthogonal range reporting queries in the case when the query range is a \emph{fat} rectangle. Our two-dimensional data structure uses $O(n)$ words and supports queries in $O(\log\log U +k)$ time, where $n$ is the number of points in the data structure, $U$ is the size of the universe and $k$ is the number of points in the query range. Our three-dimensional data structure needs $O(n\log^{\varepsilon}U)$ words of space and answers queries in $O(\log \log U + k)$ time. We also consider the rectangle stabbing problem on a set of three-dimensional fat rectangles. Our data structure uses $O(n)$ space and answers stabbing queries in $O(\log U\log\log U +k)$ time.Comment: extended version of a WADS'19 pape

Prenatal antidepressant use and risk of attention-deficit/hyperactivity disorder in offspring: population based cohort study

Objective: To assess the potential association between prenatal use of antidepressants and the risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. Design: Population based cohort study. Setting: Data from the Hong Kong population based electronic medical records on the Clinical Data Analysis and Reporting System. Participants: 190 618 children born in Hong Kong public hospitals between January 2001 and December 2009 and followed-up to December 2015. Main outcome measure: Hazard ratio of maternal antidepressant use during pregnancy and ADHD in children aged 6 to 14 years, with an average follow-up time of 9.3 years (range 7.4-11.0 years). Results: Among 190 618 children, 1252 had a mother who used prenatal antidepressants. 5659 children (3.0%) were given a diagnosis of ADHD or received treatment for ADHD. The crude hazard ratio of maternal antidepressant use during pregnancy was 2.26 (P<0.01) compared with non-use. After adjustment for potential confounding factors, including maternal psychiatric disorders and use of other psychiatric drugs, the adjusted hazard ratio was reduced to 1.39 (95% confidence interval 1.07 to 1.82, P=0.01). Likewise, similar results were observed when comparing children of mothers who had used antidepressants before pregnancy with those who were never users (1.76, 1.36 to 2.30, P<0.01). The risk of ADHD in the children of mothers with psychiatric disorders was higher compared with the children of mothers without psychiatric disorders even if the mothers had never used antidepressants (1.84, 1.54 to 2.18, P<0.01). All sensitivity analyses yielded similar results. Sibling matched analysis identified no significant difference in risk of ADHD in siblings exposed to antidepressants during gestation and those not exposed during gestation (0.54, 0.17 to 1.74, P=0.30). Conclusions: The findings suggest that the association between prenatal use of antidepressants and risk of ADHD in offspring can be partially explained by confounding by indication of antidepressants. If there is a causal association, the size of the effect is probably smaller than that reported previously.published_or_final_versio

Do temperature changes cause eczema flares? An English cohort study.

BACKGROUND: It is unclear if ambient temperature changes affect eczema. It is also unclear if people with worse disease are more susceptible to weather-related flares, or specific types of emollient offer protection. Substantiating these links may help inform action plans and patients self-management. OBJECTIVE: To investigate the effect of short-term temperature variations on eczema symptoms in children. METHODS: Data from a UK cohort of 519 children (6 months-12 years) with at least mild eczema, participating in a randomised trial comparing four types of emollients on eczema symptoms, were combined with observed temperature data from the Hadley Centre's Integrated Surface Database.Hot & cold weeks were defined by average regional temperature >75th or <25th percentile, January 2018-February 2020. Eczema flares were defined as ≥3 point change in patient-oriented eczema measure (POEM). Random effects logistic regression models were used to estimate the odds ratios of flares in hot & cold weeks (reference group: temperate weeks). The likelihood ratio test assessed for evidence of effect modification by disease severity and emollient type. RESULTS: The baseline mean age was 4.9 years (SD 3.2) and POEM score was 9.2 (SD 5.5), indicating moderate eczema. 90% of participants lived within 20 km of their nearest weather station. From the 519 participants there were 6,796 consecutively paired POEMs and 1,082 flares.Seasonal variation in POEM scores was observed, suggesting symptoms worsening with colder weather in winter and improving with warmer weather in summer. Odds ratios of flares were: 1.15 (p = 0.136, 95%CI 0.96-1.39) in cold weeks, 0.85 (p = 0.045, 95%CI 0.72-1.00) in hot weeks. Likelihood ratio test showed no evidence of this differing by disease severity (p = 0.53) or emollient type used (p = 0.55). CONCLUSIONS: Our findings are consistent with previous studies demonstrating either improvements in eczema symptoms or reduced flares in hot weather. Worse disease and different emollient types did not increase susceptibility or provide protection against temperature changes. Further work should investigate the role of sunlight, humidity, air pollution and other environmental factors

Leaf-applied sodium chloride promotes cadmium accumulation in durum wheat grain

Cadmium (Cd) accumulation in durum wheat grain is a growing concern. Among the factors affecting Cd accumulation in plants, soil chloride (Cl) concentration plays a critical role. The effect of leaf NaCl application on grain Cd was studied in greenhouse-grown durum wheat (Triticum turgidum L. durum, cv. Balcali-2000) by immersing (10 s) intact flag leaves into Cd and/or NaCl-containing solutions for 14 times during heading and dough stages. Immersing flag leaves in solutions containing increasing amount of Cd resulted in substantial increases in grain Cd concentration. Adding NaCl alone or in combination with the Cd-containing immersion solution promoted accumulation of Cd in the grains, by up to 41%. In contrast, Zn concentrations of grains were not affected or even decreased by the NaCl treatments. This is likely due to the effect of Cl complexing Cd and reducing positive charge on the metal ion, an effect that is much smaller for Zn. Charge reduction or removal (CdCl2 0 species) would increase the diffusivity/lipophilicity of Cd and enhance its capability to penetrate the leaf epidermis and across membranes. Of even more significance to human health was the ability of Cl alone to penetrate leaf tissue and mobilize and enhance shoot Cd transfer to grains, yet reducing or not affecting Zn transfer

Xenopus nerve-muscle cultures: a novel cell-based assay for serological diagnosis and pathological research of myasthenia gravis

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Reporting guidelines for clinical trials of artificial intelligence interventions: the SPIRIT-AI and CONSORT-AI guidelines

BACKGROUND: The application of artificial intelligence (AI) in healthcare is an area of immense interest. The high profile of 'AI in health' means that there are unusually strong drivers to accelerate the introduction and implementation of innovative AI interventions, which may not be supported by the available evidence, and for which the usual systems of appraisal may not yet be sufficient. MAIN TEXT: We are beginning to see the emergence of randomised clinical trials evaluating AI interventions in real-world settings. It is imperative that these studies are conducted and reported to the highest standards to enable effective evaluation because they will potentially be a key part of the evidence that is used when deciding whether an AI intervention is sufficiently safe and effective to be approved and commissioned. Minimum reporting guidelines for clinical trial protocols and reports have been instrumental in improving the quality of clinical trials and promoting completeness and transparency of reporting for the evaluation of new health interventions. The current guidelines-SPIRIT and CONSORT-are suited to traditional health interventions but research has revealed that they do not adequately address potential sources of bias specific to AI systems. Examples of elements that require specific reporting include algorithm version and the procedure for acquiring input data. In response, the SPIRIT-AI and CONSORT-AI guidelines were developed by a multidisciplinary group of international experts using a consensus building methodological process. The extensions include a number of new items that should be reported in addition to the core items. Each item, where possible, was informed by challenges identified in existing studies of AI systems in health settings. CONCLUSION: The SPIRIT-AI and CONSORT-AI guidelines provide the first international standards for clinical trials of AI systems. The guidelines are designed to ensure complete and transparent reporting of clinical trial protocols and reports involving AI interventions and have the potential to improve the quality of these clinical trials through improvements in their design and delivery. Their use will help to efficiently identify the safest and most effective AI interventions and commission them with confidence for the benefit of patients and the public

Structural Guided Scaffold Phage Display Libraries as a Source of Bio-Therapeutics

We have developed a structurally-guided scaffold phage display strategy for identification of ligand mimetic bio-therapeutics. As a proof of concept we used the ligand of integrin avb6, a tumour cell surface receptor and a major new target for imaging and therapy of many types of solid cancer. NMR structure analysis showed that RGD-helix structures are optimal for avb6 ligand-interaction, so we designed novel algorithms to generate human single chain fragment variable (scFv) libraries with synthetic VH-CDR3 encoding RGD-helix hairpins with helices of differing pitch, length and amino acid composition. Study of the lead scFv clones D25scFv and D34scFv and their corresponding VH-CDR3 derived peptides, D25p and D34p, demonstrated: specific binding to recombinant and cellular avb6; inhibition of avb6-dependent cell and ligand adhesion, avb6-dependent cell internalisation; and selective retention by avb6-expressing, but not avb6-negative, human xenografts. NMR analysis established that both the D25p and D34p retained RGD-helix structures confirming the success of the algorithm. In conclusion, scFv libraries can be engineered based on ligand structural motifs to increase the likelihood of developing powerful bio-therapeutics

Double quantum dot with integrated charge sensor based on Ge/Si heterostructure nanowires

Coupled electron spins in semiconductor double quantum dots hold promise as the basis for solid-state qubits. To date, most experiments have used III-V materials, in which coherence is limited by hyperfine interactions. Ge/Si heterostructure nanowires seem ideally suited to overcome this limitation: the predominance of spin-zero nuclei suppresses the hyperfine interaction and chemical synthesis creates a clean and defect-free system with highly controllable properties. Here we present a top gate-defined double quantum dot based on Ge/Si heterostructure nanowires with fully tunable coupling between the dots and to the leads. We also demonstrate a novel approach to charge sensing in a one-dimensional nanostructure by capacitively coupling the double dot to a single dot on an adjacent nanowire. The double quantum dot and integrated charge sensor serve as an essential building block required to form a solid-state spin qubit free of nuclear spin.Comment: Related work at http://marcuslab.harvard.edu and http://cmliris.harvard.ed