IMPORTANCE: The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. OBJECTIVE: To perform chromosomal microarray analysis ...(CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). EXPOSURES: All probands underwent CMA, with WES performed for 95 proband-parent trios. MAIN OUTCOMES AND MEASURES: The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. RESULTS: Of 258 probands, 24 (9.3%, 95% CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95% CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. For CMA, the proportion of children with a positive test result was 7 of 168 (4.2%, 95% CI, 1.7%-8.4%) in the essential group, 4 of 37 (10.8%, 95% CI, 3.0%-25.4%) in the equivocal group, and 13 of 53 (24.5%, 95% CI, 13.8%-38.3%) in the complex group (P < .001). For WES, the proportions were 2 of 64 (3.1%, 95% CI, 0.0%-10.8%), 2 of 7 (28.6%, 95% CI, 3.7%-71.0%), and 4 of 24 (16.7%, 95% CI, 4.7%-37.4%), respectively (3-group comparison, P = .02). Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95% CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined molecular diagnostic yield was 6.3% (95% CI, 1.7%-15.2%) in the essential group (4/64 children), 28.6% (95% CI, 3.7%-71.0%) in the equivocal group (2/7 children), and 37.5% (95% CI, 18.8%-59.4%) in the complex group (9/24 children; 3-group comparison, P = .001). The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). CONCLUSIONS AND RELEVANCE: Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.
A Li-ion capacitor (LIC), typically composed of a pre-lithiated negative electrode and an activated-carbon positive electrode, can provide high energy and power density. In this work, we compare the ...electrochemical performances of pre-lithiated graphene nanosheets and conventional graphite as negative electrode materials for LICs. The LICs employing pre-lithiated graphene nanosheets show a specific capacitance of 168.5 F g−1 with 74% capacitance retention at 400 mA g−1 after 300 cycles. Moreover, the capacitors deliver a maximum power density of 222.2 W kg−1 at an energy density of 61.7 Wh kg−1, operated in the voltage range of 2.0–4.0 V. Therefore, pre-lithiated graphene nanosheets are promising negative electrode materials for high power LICs.
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•Pre-lithiated graphene nanosheets are explored for Li-ion capacitors.•The Li-ion capacitors exhibit high energy and power density at high voltages.•Pre-lithiated graphene nanosheets are promising for high power Li-ion capacitors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A space‐confined “sauna” reaction system is introduced for the simultaneous reduction and functionalization of graphene oxide to unique graphene–sulfur hybrid nanosheets, in which thin layers of ...amorphous sulfur are tightly anchored on the graphene sheet via strong chemical bonding. Upon being used as the cathode material in lithium–sulfur batteries, the as‐synthesized composite shows an excellent electrochemical performance.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Arsenic in groundwater caused the black‐foot disease (BFD) in many countries in the 1950–1960s. It is of great importance to develop a feasible method for removal of arsenic from contaminated ...groundwater in BFD endemic areas. Photocatalytic oxidation of As(III) to less toxic As(V) is, therefore, of significance for preventing any arsenic‐related disease that may occur. By in situ synchrotron X‐ray absorption spectroscopy, the formation of As(V) is related to the expense of As(III) disappearance during photocatalysis by TiO2 nanotubes (TNTs). Under UV/Vis light irradiation, the apparent first‐order rate constant for the photocatalytic oxidation of As(III) to As(V) is 0.0148 min−1. It seems that As(III) can be oxidized with photo‐excited holes while the not‐recombined electrons may be scavenged with O2 in the channels of the well defined TNTs (an opening of 7 nm in diameter). In the absence of O2, on the contrary, As(III) can be reduced to As(0), to some extent. Cu(II) (CuO), as an electron acceptor, was impregnated on the TNTs surfaces in order to gain a better understanding of electron transfer during photocatalysis. It appears that As(III) can be oxidized to As(V) while Cu(II) is reduced to Cu(I) and Cu(0). The molecular‐scale data are very useful in revealing the oxidation states and interconversions of arsenic during the photocatalytic reactions. This work has implications in that the toxicity of arsenic in contaminated groundwater or wastewater can be effectively decreased via solar‐driven photocatalysis, which may facilitate further treatments by coagulation.
The photocatalytic oxidation of As(III) to less toxic As(V) by TiO2 nanotubes studied using in situ synchrotron X‐ray absorption spectroscopy is presented.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Neurosteroids are endogenous modulators of neuronal excitability and nervous system development and are being developed as anesthetic agents and treatments for psychiatric diseases. While gamma ...amino-butyric acid Type A (GABAA) receptors are the primary molecular targets of neurosteroid action, the structural details of neurosteroid binding to these proteins remain ill defined. We synthesized neurosteroid analogue photolabeling reagents in which the photolabeling groups were placed at three positions around the neurosteroid ring structure, enabling identification of binding sites and mapping of neurosteroid orientation within these sites. Using middle-down mass spectrometry (MS), we identified three clusters of photolabeled residues representing three distinct neurosteroid binding sites in the human α1β3 GABAA receptor. Novel intrasubunit binding sites were identified within the transmembrane helical bundles of both the α1 (labeled residues α1-N408, Y415) and β3 (labeled residue β3-Y442) subunits, adjacent to the extracellular domains (ECDs). An intersubunit site (labeled residues β3-L294 and G308) in the interface between the β3(+) and α1(-) subunits of the GABAA receptor pentamer was also identified. Computational docking studies of neurosteroid to the three sites predicted critical residues contributing to neurosteroid interaction with the GABAA receptors. Electrophysiological studies of receptors with mutations based on these predictions (α1-V227W, N408A/Y411F, and Q242L) indicate that both the α1 intrasubunit and β3-α1 intersubunit sites are critical for neurosteroid action.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although cancer often is referred to as “a disease of the genes,” it is indisputable that the (epi)genetic properties of individual cancer cells are highly variable, even within the same tumor. ...Hence, preexisting resistant clones will emerge and proliferate after therapeutic selection that targets sensitive clones. Herein, the authors propose that quantitative image analytics, known as “radiomics,” can be used to quantify and characterize this heterogeneity. Virtually every patient with cancer is imaged radiologically. Radiomics is predicated on the beliefs that these images reflect underlying pathophysiologies, and that they can be converted into mineable data for improved diagnosis, prognosis, prediction, and therapy monitoring. In the last decade, the radiomics of cancer has grown from a few laboratories to a worldwide enterprise. During this growth, radiomics has established a convention, wherein a large set of annotated image features (1‐2000 features) are extracted from segmented regions of interest and used to build classifier models to separate individual patients into their appropriate class (eg, indolent vs aggressive disease). An extension of this conventional radiomics is the application of “deep learning,” wherein convolutional neural networks can be used to detect the most informative regions and features without human intervention. A further extension of radiomics involves automatically segmenting informative subregions (“habitats”) within tumors, which can be linked to underlying tumor pathophysiology. The goal of the radiomics enterprise is to provide informed decision support for the practice of precision oncology.
Virtually every patient with cancer is radiologically imaged. The field of radiomics combines quantitative analysis of these images with machine learning to improve diagnosis, prognosis, prediction, and therapy monitoring. This review describes radiomics including novel artificial intelligence methods, and introduces the practice of defining subregions, or “habitats,” within tumors.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary Background The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its ...efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4–10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov , number NCT01896635 . The trial has ended; this report presents the final analysis. Findings From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1–11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission. Interpretation Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor–recipient matching based on microbial profiles. Funding Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Two different thermal conditions are established to explore the lithium-ion battery performance.•Battery pack without BTMS intervention may have an excellent discharging performance.•Battery ...charging performance is independent on the charging temperature ranged from 20 °C to 40 °C.•The irreversible heat can be regarded as the sole heat source term to simplify battery thermal model.
The relationship between lithium-ion battery performance and operating temperature is of significance in designing battery thermal management system (BTMS). In this study, two different thermal conditions, namely constant temperature condition and near-adiabatic condition are established to explore charging/discharging characteristics and heat generation behaviors of the lithium-ion battery with Li(NixCoyAlz)O2 cathode. The objective of creating near-adiabatic condition is to discover the effect of the heat generated by battery itself on charging/discharging characteristics. The experimental results show that the battery charging characteristics are nearly independent on the charging temperature ranged from 20 °C to 40 °C, while the battery charging/discharging performance degrade dramatically for the battery temperature lower than 20 °C. Although the heat generated by battery itself may accelerate battery degradation during cycling due to the adverse effect of excessive temperature, however it improves the discharging performance in a suitable temperature range. This implies that a battery pack may have an excellent discharging performance without BTMS intervention at a moderate discharging rate (e.g., 0.5 C). The irreversible heat could be regarded as the sole heat source term to simplify the battery thermal model due to negligible thermal effect caused by the small amount of reversible heat when the battery is discharged at higher discharging rates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
he prevalence of frailty defined by FRAIL-NH varies among different studies in nursing homes, ranging from 19.0% to 75.6%. This study investigated the prevalence of frailty in a nursing ...home in Taiwan using different diagnostic criteria for frailty.
Methods
The 7-item FRAIL-NH scale was used for assessing frailty. There are 7 components: fatigue, resistance, mobility, incontinence or disease, weight loss, eating style and assistance with dressing. Each item is worth 0, 1, or 2 points for a total score of 14 points. We sorted and summarized the patients, according to the number of variables, into the not frail, frail, and most frail groups. Descriptive analysis was applied to understand the basic attributes of the elderly with different degrees of frailty, the influencing factors of frailty, and the occurrence of frailty.
Results
Our final sample included 34 residents. They were aged between 56 and 100 years (mean age 83.91 ± 10.84), and 18 (52.94%) were female. The frail group revealed a higher prevalence of males than of females. The marital status composition of participants was as follows: 2 (5.88%) unmarried, 24 (70.59%) married, and 8 (23.53%) widowed. The mean FRAIL-NH score was 5.79±3.72.
Conclusions
A significant prevalence of frailty defined by FRAIL-NH was observed in a nursing home in Taiwan. Our findings indicate that frailty is an important issue in nursing homes. Further prospective cohort studies using FRAIL-NH evaluation are warranted.
TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) ...therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP–treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 507 cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP–treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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