Room-temperature spin injection across a chiral perovskite/III-V interface.

Spin accumulation in semiconductor structures at room temperature and without magnetic fields is key to enable a broader range of optoelectronic functionality1. Current efforts are limited owing to inherent inefficiencies associated with spin injection across semiconductor interfaces2. Here we demonstrate spin injection across chiral halide perovskite/III-V interfaces achieving spin accumulation in a standard semiconductor III-V (AlxGa1-x)0.5In0.5P multiple quantum well light-emitting diode. The spin accumulation in the multiple quantum well is detected through emission of circularly polarized light with a degree of polarization of up to 15 ± 4%. The chiral perovskite/III-V interface was characterized with X-ray photoelectron spectroscopy, cross-sectional scanning Kelvin probe force microscopy and cross-sectional transmission electron microscopy imaging, showing a clean semiconductor/semiconductor interface at which the Fermi level can equilibrate. These findings demonstrate that chiral perovskite semiconductors can transform well-developed semiconductor platforms into ones that can also control spin.

Metal Halide Perovskite Heterostructures: Blocking Anion Diffusion with Single-Layer Graphene.

The development of metal halide perovskite/perovskite heterostructures is hindered by rapid interfacial halide diffusion leading to mixed alloys rather than sharp interfaces. To circumvent this outcome, we developed an ion-blocking layer consisting of single-layer graphene (SLG) deposited between the metal halide perovskite layers and demonstrated that it effectively blocks anion diffusion in a CsPbBr3/SLG/CsPbI3 heterostructure. Spatially resolved elemental analysis and spectroscopic measurements demonstrate the halides do not diffuse across the interface, whereas control samples without the SLG show rapid homogenization of the halides and loss of the sharp interface. Ultraviolet photoelectron spectroscopy, DFT calculations, and transient absorbance spectroscopy indicate the SLG has little electronic impact on the individual semiconductors. In the CsPbBr3/SLG/CsPbI3, we find a type I band alignment that supports transfer of photogenerated carriers across the heterointerface. Light-emitting diodes (LEDs) show electroluminescence from both the CsPbBr3 and CsPbI3 layers with no evidence of ion diffusion during operation. Our approach provides opportunities to design novel all-perovskite heterostructures to facilitate the control of charge and light in optoelectronic applications.

Identification and Characterization of Colletotrichum Species Associated with Cherry Leaf Spot Disease in China.

Leaf spot is a common and serious disease of sweet cherry worldwide and has become a major concern in China. From 2018 to 2020, disease investigations were carried out in Beijing City, Sichuan, Shandong, and Liaoning Provinces in China, and 105 Colletotrichum isolates were obtained from diseased samples. Isolates were identified by morphological characterization coupled with multigene phylogenetic analyses based on six loci (internal transcribed spacer region, glyceraldehyde 3-phosphate dehydrogenase, calmodulin, actin, chitin synthase, and ß-tubulin). A total of 13 Colletotrichum species were identified, namely Colletotrichum aenigma, C. gloeosporioides, C. fructicola, C. siamense, C. temperatum, C. conoides, C. hebeiense, C. sojae, C. plurivorum, C. karsti, C. truncatum, C. incanum, and C. dematium. Among these, C. aenigma (25.7%) was the most prominent species isolated from diseased leaves, followed by C. gloeosporioides (19.0%) and C. fructicola (12.4%). Pathogenicity was tested on detached leaves of cv. 'Tieton' and 'Summit' and young seedlings of cv. 'Brooks' under greenhouse conditions. All 13 species were pathogenic to cherry leaves, and C. aenigma, C. conoides, and C. dematium showed high levels of virulence. Seedlings inoculated with the isolates developed similar symptoms to those seen in the orchards. This study provides the first reports for 11 of the 13 Colletotrichum species on sweet cherry in the world, excluding C. aenigma and C. fructicola. This is the first comprehensive study of Colletotrichum species associated with cherry leaf spot in China, and the results will provide basic knowledge to develop sustainable control measures for cherry leaf spot.

Improving early phase oncology clinical trial design: An opportunity for statisticians.

This short communication supports that rule-based study designs such as the '3 + 3' study design are still being used in early phase oncology development programs despite their inferior performance to model-based and model-assisted designs. Statisticians have an opportunity to shape and improve early phase oncology drug development programs by introducing newer, more efficient study designs that estimate the Optimal Biological dose to their oncology trialist colleges.

Web based resource for Statistical Consultants in the Pharmaceutical Industry.

The intention of this article is to highlight sources of web-based reference material and software that will aid consulting statisticians when designing clinical trials. The article includes websites that provide links to explanation of statistical concepts for non-statisticians, regulatory guidelines, and free statistical study design software.

Improving early phase oncology clinical trial design: The case for finding the optimal biological dose.

Historically early phase oncology drug development programmes have been based on the belief that "more is better". Furthermore, rule-based study designs such as the "3 + 3" design are still often used to identify the MTD. Phillips and Clark argue that newer Bayesian model-assisted designs such as the BOIN design should become the go to designs for statisticians for MTD finding. This short communication goes one stage further and argues that Bayesian model-assisted designs such as the BOIN12 which balances risk-benefit should be included as one of the go to designs for early phase oncology trials, depending on the study objectives. Identifying the optimal biological dose for future research for many modern targeted drugs, immunotherapies, cell therapies and vaccine therapies can save significant time and resources.

Improving early phase oncology clinical trial design: A case study.

This short communication presents a first in human Bayesian Optimal Interval design case study. The study design and associated operating characteristics are discussed, together with study amendments proposed whilst the study was ongoing. Simulations investigating the impact of the amendments on the operating characteristics of the study design are presented. Lessons learnt from the case study, including providing practical advice when designing smarter early phase oncology trials to identify the maximum tolerate dose are also summarised. It is argued that model-assisted designs are simple to implement, flexible and perform significantly better than the commonly used "3 + 3" design, and thus should become the go to design for statisticians when limited information is known about the dose toxicity curve.

Estimands in practice: Bridging the gap between study objectives and statistical analysis.

The International Council for Harmonisation (ICH) guideline E9 Statistical Principles for Clinical Trials (1) was issued in 1998. In October 2014, an addendum to ICH E9 was proposed on statistical principles relating to estimands and sensitivity analyses. The final version of the addendum to ICH E9 (R1) (2) was issued in November 2019. This virtual edition of Pharmaceutical Statistics takes a closer look at some of the progress that has been made since 2018 when implementing the estimand framework within clinical research. The articles discussed in this virtual issue are not new, but a compilation from previous issues. This specific article will act as a refresher for those not familiar with the topic and discuss the ABCs of estimands and their proposed deployment for improving the quality of clinical research. An overview of the more recent Pharmaceutical Statistics articles on estimands will be provided, signifying areas where progress have been made. The articles should be considered as contributions to the ongoing discussions rather than the final word. Finally, a personal perspective on the estimand success story and remaining challenges with proposed solutions will be discussed.

Fungal diversity notes 1387-1511: taxonomic and phylogenetic contributions on genera and species of fungal taxa.

This article is the 13th contribution in the Fungal Diversity Notes series, wherein 125 taxa from four phyla, ten classes, 31 orders, 69 families, 92 genera and three genera incertae sedis are treated, demonstrating worldwide and geographic distribution. Fungal taxa described and illustrated in the present study include three new genera, 69 new species, one new combination, one reference specimen and 51 new records on new hosts and new geographical distributions. Three new genera, Cylindrotorula (Torulaceae), Scolecoleotia (Leotiales genus incertae sedis) and Xenovaginatispora (Lindomycetaceae) are introduced based on distinct phylogenetic lineages and unique morphologies. Newly described species are Aspergillus lannaensis, Cercophora dulciaquae, Cladophialophora aquatica, Coprinellus punjabensis, Cortinarius alutarius, C. mammillatus, C. quercoflocculosus, Coryneum fagi, Cruentomycena uttarakhandina, Cryptocoryneum rosae, Cyathus uniperidiolus, Cylindrotorula indica, Diaporthe chamaeropicola, Didymella azollae, Diplodia alanphillipsii, Dothiora coronicola, Efibula rodriguezarmasiae, Erysiphe salicicola, Fusarium queenslandicum, Geastrum gorgonicum, G. hansagiense, Helicosporium sexualis, Helminthosporium chiangraiensis, Hongkongmyces kokensis, Hydrophilomyces hydraenae, Hygrocybe boertmannii, Hyphoderma australosetigerum, Hyphodontia yunnanensis, Khaleijomyces umikazeana, Laboulbenia divisa, Laboulbenia triarthronis, Laccaria populina, Lactarius pallidozonarius, Lepidosphaeria strobelii, Longipedicellata megafusiformis, Lophiotrema lincangensis, Marasmius benghalensis, M. jinfoshanensis, M. subtropicus, Mariannaea camelliae, Melanographium smilaxii, Microbotryum polycnemoides, Mimeomyces digitatus, Minutisphaera thailandensis, Mortierella solitaria, Mucor harpali, Nigrograna jinghongensis, Odontia huanrenensis, O. parvispina, Paraconiothyrium ajrekarii, Parafuscosporella niloticus, Phaeocytostroma yomensis, Phaeoisaria synnematicus, Phanerochaete hainanensis, Pleopunctum thailandicum, Pleurotheciella dimorphospora, Pseudochaetosphaeronema chiangraiense, Pseudodactylaria albicolonia, Rhexoacrodictys nigrospora, Russula paravioleipes, Scolecoleotia eriocamporesi, Seriascoma honghense, Synandromyces makranczyi, Thyridaria aureobrunnea, Torula lancangjiangensis, Tubeufia longihelicospora, Wicklowia fusiformispora, Xenovaginatispora phichaiensis and Xylaria apiospora. One new combination, Pseudobactrodesmium stilboideus is proposed. A reference specimen of Comoclathris permunda is designated. New host or distribution records are provided for Acrocalymma fici, Aliquandostipite khaoyaiensis, Camarosporidiella laburni, Canalisporium caribense, Chaetoscutula juniperi, Chlorophyllum demangei, C. globosum, C. hortense, Cladophialophora abundans, Dendryphion hydei, Diaporthe foeniculina, D. pseudophoenicicola, D. pyracanthae, Dictyosporium pandanicola, Dyfrolomyces distoseptatus, Ernakulamia tanakae, Eutypa flavovirens, E. lata, Favolus septatus, Fusarium atrovinosum, F. clavum, Helicosporium luteosporum, Hermatomyces nabanheensis, Hermatomyces sphaericoides, Longipedicellata aquatica, Lophiostoma caudata, L. clematidis-vitalbae, Lophiotrema hydei, L. neoarundinaria, Marasmiellus palmivorus, Megacapitula villosa, Micropsalliota globocystis, M. gracilis, Montagnula thailandica, Neohelicosporium irregulare, N. parisporum, Paradictyoarthrinium diffractum, Phaeoisaria aquatica, Poaceascoma taiwanense, Saproamanita manicata, Spegazzinia camelliae, Submersispora variabilis, Thyronectria caudata, T. mackenziei, Tubeufia chiangmaiensis, T. roseohelicospora, Vaginatispora nypae, Wicklowia submersa, Xanthagaricus necopinatus and Xylaria haemorrhoidalis. The data presented herein are based on morphological examination of fresh specimens, coupled with analysis of phylogenetic sequence data to better integrate taxa into appropriate taxonomic ranks and infer their evolutionary relationships.

Estimands: discussion points from the PSI estimands and sensitivity expert group.

ICH E9 Statistical Principles for Clinical Trials was issued in 1998. In October 2014, an addendum to ICH E9 was proposed relating to estimands and sensitivity analyses. In preparation for the release of the addendum, Statisticians in the Pharmaceutical Industry held a 1-day expert group meeting in February 2015. Topics debated included definition, development, implementation, education and communication challenges associated with estimands and sensitivity analyses. The topic of estimands is an important and relatively new one in clinical development. A clear message from the meeting was that estimands bridge the gap between study objectives and statistical methods. When defining estimands, an iterative process linking trial objectives, estimands, trial design, statistical and sensitivity analysis needs to be established. Each objective should have at least one distinct estimand, supported by sensitivity analyses. Because clinical trials are multi-faceted and expensive, it is unrealistic to restrict a study to a single objective and associated estimand. The actual set of estimands and sensitivity analyses for a study will depend on the study objectives, the disease setting and the needs of the various stakeholders. Copyright © 2016 John Wiley & Sons, Ltd.

Shiga toxin production and translocation during microaerobic human colonic infection with Shiga toxin-producing E. coli†O157:H7 and O104:H4.

Haemolytic uraemic syndrome caused by Shiga toxin-producing E. coli (STEC) is dependent on release of Shiga toxins (Stxs) during intestinal infection and subsequent absorption into the bloodstream. An understanding of Stx-related events in the human gut is limited due to lack of suitable experimental models. In this study, we have used a vertical diffusion chamber system with polarized human colon carcinoma cells to simulate the microaerobic (MA) environment in the human intestine and investigate its influence on Stx release and translocation during STEC O157:H7 and O104:H4 infection. Stx2 was the major toxin type released during infection. Whereas microaerobiosis significantly reduced bacterial growth as well as Stx production and release into the medium, Stx translocation across the epithelial monolayer was enhanced under MA versus aerobic conditions. Increased Stx transport was dependent on STEC infection and occurred via a transcellular pathway other than macropinocytosis. While MA conditions had a similar general effect on Stx release and absorption during infection with STEC O157:H7 and O104:H4, both serotypes showed considerable differences in colonization, Stx production, and Stx translocation which suggest alternative virulence strategies. Taken together, our study suggests that the MA environment in the human colon may modulate Stx-related events and enhance Stx absorption during STEC infection.

Paneth cell metaplasia in newly diagnosed inflammatory bowel disease in children.

BACKGROUND: Paneth cell metaplasia (PCM) is well described in adults but little is known about the distribution of colonic Paneth cells and the occurrence of PCM in a paediatric population. The aim of this study is to determine whether Paneth cell hyperplasia or metaplasia characteristically occurs in the colons of children with newly diagnosed idiopathic inflammatory bowel disease (IBD). METHODS: We retrospectively reviewed colonic series from 28 new diagnoses of paediatric IBD at a tertiary referral centre, and from a further 14 children with IBD-like symptoms whose colonic biopsies and ancillary investigations were normal. Paneth cells were counted at 6 anatomical sites in the colon, and at each site acute and chronic inflammation were assessed semi-quantitatively and the presence or absence of crypt architectural distortion and eosinophilia was documented. RESULTS: In control, ulcerative colitis (UC) and Crohn's disease (CD) groups there was a gradient of decreasing Paneth cell numbers from caecum to rectum. Paneth cells were not seen in the distal colon in the control group, but they were present there in 11 of 13 patients with ulcerative colitis and 14 of 15 with Crohn's disease. Only patients with IBD showed Paneth cell hyperplasia, assessed as more than 10 Paneth cells per 10 well-oriented crypts at any site. There was a statistically significant increase in Paneth cells in the caecum, ascending, transverse and descending colon in UC and in the ascending, transverse, descending and sigmoid colon in CD compared with controls. There was no significant difference between UC and CD. There was no correlation between the site of PCM and acute or chronic inflammation, crypt distortion or eosinophilia. CONCLUSION: Paneth cells are found in the proximal but not the distal colon in otherwise normal paediatric colonic series. A high proportion of UC and CD patients show PCM in the distal colon. This is present early in the disease and does not correlate with histological features of chronicity.

Research and the promotion of child health: a position paper of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Children comprise one-fifth of Europe's population. Promoting child health and development is of key importance for society and its future. This position paper highlights opportunities of investing in gastrointestinal, liver, and nutritional research to promote child health and delineates priorities for research. Investing in child health plays a key role in the promotion of population health, well-being, and disease prevention lifelong, with large health economic benefits. Major opportunities for improving knowledge and translational application arise from recent scientific and technological developments, for example, the long-term impact of early environmental cues interacting with genes. Personalised approaches to therapy and prevention should be enhanced. Deciphering the microbiome and its effects on functions can help in promoting long-term health. Epigenetic research can help to understand how early environmental factors influence later gastrointestinal and hepatic health and disease. A linked nutrition and physical activity strategy can promote health and prevent nutritional deficiencies, inactivity, and chronic noncommunicable diseases, such as diabetes, to ensure optimal health and cognition. Special attention should be devoted to populations with low socioeconomic status, migrant background, and ethnic minorities, and to critical life periods, including pregnancy, lactation, infancy, and childhood. Improved understanding of optimal nutrition and on maintaining gut and liver homeostasis throughout childhood will help prevent chronic diseases in later life.

Public-private collaboration in clinical research during pregnancy, lactation, and childhood: joint position statement of the Early Nutrition Academy and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

This position statement summarises a view of academia regarding standards for clinical research in collaboration with commercial enterprises, focussing on trials in pregnant women, breast-feeding women, and children. It is based on a review of the available literature and an expert workshop cosponsored by the Early Nutrition Academy and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. Clinical research collaborations between academic investigators and commercial enterprises are encouraged by universities, public funding agencies, and governmental organisations. One reason is a pressing need to obtain evidence on the effects, safety, and benefits of drugs and other commercial products and services. The credibility and value of results obtained through public-private research collaborations have, however, been questioned because many examples of inappropriate research practice have become known. Clinical research in pregnant and breast-feeding women, and in infants and children, raises sensitive scientific, ethical, and societal questions and requires the application of particularly high standards. Here we provide recommendations for the conduct of public-private research collaborations in these populations. In the interest of all stakeholders, these recommendations should contribute to more reliable, credible, and acceptable results of commercially sponsored trials and to reducing the existing credibility gap.

Naming and outline of Dothideomycetes-2014 including proposals for the protection or suppression of generic names.

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and nonpleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data.

Some issues in predicting patient recruitment in multi-centre clinical trials.

A key paper in modelling patient recruitment in multi-centre clinical trials is that of Anisimov and Fedorov. They assume that the distribution of the number of patients in a given centre in a completed trial follows a Poisson distribution. In a second stage, the unknown parameter is assumed to come from a Gamma distribution. As is well known, the overall Gamma-Poisson mixture is a negative binomial. For forecasting time to completion, however, it is not the frequency domain that is important, but the time domain and that of Anisimov and Fedorov have also illustrated clearly the links between the two and the way in which a negative binomial in one corresponds to a type VI Pearson distribution in the other. They have also shown how one may use this to forecast time to completion in a trial in progress. However, it is not just necessary to forecast time to completion for trials in progress but also for trials that have yet to start. This suggests that what would be useful would be to add a higher level of the hierarchy: over all trials. We present one possible approach to doing this using an orthogonal parameterization of the Gamma distribution with parameters on the real line. The two parameters are modelled separately. This is illustrated using data from 18 trials. We make suggestions as to how this method could be applied in practice.

Phylogeny and taxonomy of Botryosphaeria and Neofusicoccum species in Iran, with description of Botryosphaeria scharifii sp. nov.

Species of Botryosphaeriaceae are important pathogens and endophytes associated with woody plants. Botryosphaeria and Neofusicoccum are two well known genera of the family. In this study 125 isolates morphologically resembling members of this family were collected from about 20 different fruit and forest trees in Iran. Based on morphology, MSP-PCR profile and DNA sequence data (ITS and tef1-a), four species were identified. Of these, Botryosphaeria dothidea, Neofusicoccum mediterraneum and N. parvum are known while Botryosphaeria scharifii is described here as new. N. mediterraneum is a new record for Iran and is reported here for the first time on mango trees. High diversity within Iranian population of N. parvum suggests the need to revise and reassess the morphological species description of N. parvum and closely related species.