Resetting of the 24-nt siRNA landscape in rice zygotes.

The zygote, a totipotent stem cell, is crucial to the life cycle of sexually reproducing organisms. It is produced by the fusion of two differentiated cells-the egg and sperm, which in plants have radically different siRNA transcriptomes from each other and from multicellular embryos. Owing to technical challenges, the epigenetic changes that accompany the transition from differentiated gametes to totipotent zygote are poorly understood. Because siRNAs serve as both regulators and outputs of the epigenome, we characterized small RNA transcriptomes of zygotes from rice. Zygote small RNAs exhibit extensive maternal carryover and an apparent lack of paternal contribution, indicated by absence of sperm signature siRNAs. Zygote formation is accompanied by widespread redistribution of 24-nt siRNAs relative to gametes, such that ∼70% of the zygote siRNA loci do not overlap any egg cell siRNA loci. Newly detected siRNA loci in zygote are gene-proximal and not associated with centromeric heterochromatin, similar to canonical siRNAs, in sharp contrast to gametic siRNA loci that are gene-distal and heterochromatic. In addition, zygote but not egg siRNA loci are associated with high DNA methylation in the mature embryo. Thus, the zygote begins transitioning before the first embryonic division to an siRNA profile that is associated with future RdDM in embryogenesis. These findings indicate that, in addition to changes in gene expression, the transition to totipotency in the plant zygote is accompanied by resetting of the epigenetic reprogramming that occurred during gamete formation.

That's out! How expert umpires make leg-before-wicket judgements in cricket.

Despite evidence that elite-level cricket umpires are highly accurate in making leg-before-wicket (LBW) judgements, there is limited understanding as to how they make these judgements. In this study, we explored the explicit LBW decision-making expertise of elite-level cricket umpires (N = 10) via 10 individual semi-structured interviews. Using thematic analysis, we aimed to identify the sources of information that umpires incorporate into their decision-making process. Results indicated that umpires engage in intentional pre-delivery information-gathering to guide their expectations, and to set context-specific parameters as to what would constitute an LBW dismissal. Not only do umpires use information about the ball trajectory, but they also use additional information about the condition of the pitch, the action-capabilities and susceptibilities of players, and the unique requirements of different match formats. Umpires reported employing a gaze-anchor strategy when gathering information for each delivery and described the process of this information as initially intuitive, before engaging in deeper post-hoc reasoning. Findings highlight the importance of including contextual information when exploring officials' decisions and may inform future training interventions for cricket umpires.

Dialect identification, intelligibility ratings, and acceptability ratings of dysarthric speech in two American English dialects.

The current study explored the intelligibility and acceptability ratings of dysarthric speakers with African American English (AAE) and General American English (GAE) dialects by listeners who identify as GAE or AAE speakers, as well as listener ability to identify dialect in dysarthric speech. Eighty-six listeners rated the intelligibility and acceptability of sentences extracted from a passage read by speakers with dysarthria. Samples were used from the Atlanta Motor Speech Disorders Corpus and ratings were collected via self-report. The listeners identified speaker dialect in a forced-choice format. Listeners self-reported their dialect and exposure to AAE. AAE dialect was accurately identified in 63.43% of the the opportunities; GAE dialect was accurately identified in 70.35% of the opportunities. Listeners identifying as AAE speakers rated GAE speech as more acceptable, whereas, listeners identifying as GAE speakers rated AAE speech as more acceptable. Neither group of listeners demonstrated a difference in intelligibility ratings. Exposure to AAE had no effect on intelligibility or acceptability ratings. Listeners can identify dialect (AAE and GAE) with a better than chance degree of accuracy. One's dialect may have an effect on intelligibility and acceptability ratings. Exposure to a dialect did not affect listener ratings of intelligibility or acceptability.

Genome-wide redistribution of 24-nt siRNAs in rice gametes.

Gametes constitute a critical stage of the plant life cycle during which the genome undergoes reprogramming in preparation for embryogenesis. Here, we examined genome-wide distributions of small RNAs in the sperm and egg cells of rice. We found that 24-nt siRNAs, which are a hallmark of RNA-directed DNA methylation (RdDM) in plants, were depleted from heterochromatin boundaries in both gametes relative to vegetative tissues, reminiscent of siRNA patterns in DDM1-type nucleosome remodeler mutants. In sperm cells, 24-nt siRNAs were spread across heterochromatic regions, while in egg cells, 24-nt siRNAs were concentrated at a smaller number of heterochromatic loci throughout the genome, especially at loci which also produced siRNAs in other tissues. In both gametes, patterns of CHH methylation, typically a strong indicator of RdDM, were similar to vegetative tissues, although lower in magnitude. These findings indicate that the small RNA transcriptome undergoes large-scale redistribution in both male and female gametes, which is not correlated with recruitment of DNA methyltransferases in gametes and suggestive of unexplored regulatory activities of gamete small RNAs.

Does the method of telehealth delivery affect the physiotherapy management of adults with bleeding disorders? A comparison of audioconferencing and videoconferencing.

AIM: To determine whether the method of telehealth delivery (audioconferencing or videoconferencing) affects the physiotherapy management of adults with inherited bleeding disorders. METHODS: A cross-sectional observational study was utilised involving 40 physiotherapy consultations (23 initial consultations and 17 follow-up consultations) of adults (>18) with a diagnosed bleeding disorder. Each consultation involved an initial audioconferencing component followed immediately by a separate videoconferencing component. Following each component, the physiotherapist utilised the clinical information gathered to formulate and record a management plan, and additionally recorded their confidence in this plan. Differences between the management plans and clinician confidence were recorded, including where applicable the visual information prompting a change in management plans. RESULTS: Audioconferencing and videoconferencing management plans differed in 40% of all consultations, including 52.0% of initial consultations and 23.5% of follow-up consultations. Among consultations where management plans differed, this was prompted by visual information related to the anatomic location of symptoms (31.3%), the absence/presence of swelling (31.3%), joint range of movement (25.0%), and general appearance (12.5%). Median self-reported clinician confidence of management plans increased significantly from 70.0% following audioconferencing to 93.0% following videoconferencing. CONCLUSION: When utilizing telehealth, the choice between audioconferencing or videoconferencing may affect physiotherapy management of adults with bleeding disorders, particularly with initial consultations. Videoconferencing potentially leads to more appropriate management plans, clinician confidence and utilization of healthcare resources. Further high-quality studies are required to confirm the findings of this study.

The future of rare disease drug development: the rare disease cures accelerator data analytics platform (RDCA-DAP).

Rare disease drug development is wrought with challenges not the least of which is access to the limited data currently available throughout the rare disease ecosystem where sharing of the available data is not guaranteed. Most pharmaceutical sponsors seeking to develop agents to treat rare diseases will initiate data landscaping efforts to identify various data sources that might be informative with respect to disease prevalence, patient selection and identification, disease progression and any data projecting likelihood of patient response to therapy including any genetic data. Such data are often difficult to come by for highly prevalent, mainstream disease populations let alone for the 8000 rare disease that make up the pooled patient population of rare disease patients. The future of rare disease drug development will hopefully rely on increased data sharing and collaboration among the entire rare disease ecosystem. One path to achieving this outcome has been the development of the rare disease cures accelerator, data analytics platform (RDCA-DAP) funded by the US FDA and operationalized by the Critical Path Institute. FDA intentions were clearly focused on improving the quality of rare disease regulatory applications by sponsors seeking to develop treatment options for various rare disease populations. As this initiative moves into its second year of operations it is envisioned that the increased connectivity to new and diverse data streams and tools will result in solutions that benefit the entire rare disease ecosystem and that the platform becomes a Collaboratory for engagement of this ecosystem that also includes patients and caregivers.

Understanding the Constipation Conundrum: Predictors of Obtaining an Abdominal Radiograph During the Emergency Department Evaluation of Pediatric Constipation.

OBJECTIVES: Many children with constipation who are evaluated in emergency departments (EDs) receive an abdominal radiograph (AR) despite evidence-based guidelines discouraging imaging. The objectives of this study were to identify predictors associated with obtaining an AR and to determine if ARs were associated with a longer length of stay (LOS) among children with constipation evaluated in the ED. METHODS: A review of billing and electronic health records was conducted in an academic pediatric ED for children ages 0 to 17 years who had a primary discharge diagnosis of constipation from July 2013 to June 2014. Logistic regression was used to identify predictors for obtaining an AR. Differences in mean LOS were analyzed using linear regression. RESULTS: In total, 326 children met inclusion criteria, and 60% of the children received an AR. In logistic regression, significant predictors included age (odds ratio [OR] = 1.1/year of age, P = 0.004), presenting with abdominal pain as chief complaint compared with constipation (OR = 4.4, P < 0.0001), and history of emesis (OR = 2.8, P = 0.001) after controlling for provider type and previous constipation medication use. In linear regression, the adjusted mean LOS for those with an AR was 163 minutes compared with 117 minutes for those without after controlling for age, provider type, and history of constipation medication use (P < 0.0001). CONCLUSIONS: Abdominal radiographs were used frequently in the ED diagnosis and management of constipation, particularly in older children and those with abdominal pain and emesis. Abdominal radiographs were associated with increased LOS.

Cis-Regulatory Elements Determine Germline Specificity and Expression Level of an Isopentenyltransferase Gene in Sperm Cells of Arabidopsis.

Flowering plant sperm cells transcribe a divergent and complex complement of genes. To examine promoter function, we chose an isopentenyltransferase gene known as PzIPT1. This gene is highly selectively transcribed in one sperm cell morphotype of Plumbago zeylanica, which preferentially fuses with the central cell during fertilization and is thus a founding cell of the primary endosperm. In transgenic Arabidopsis (Arabidopsis thaliana), PzIPT1 promoter displays activity in both sperm cells and upon progressive promoter truncation from the 5'-end results in a progressive decrease in reporter production, consistent with occurrence of multiple enhancer sites. Cytokinin-dependent protein binding motifs are identified in the promoter sequence, which respond with stimulation by cytokinin. Expression of PzIPT1 promoter in sperm cells confers specificity independently of previously reported Germline Restrictive Silencer Factor binding sequence. Instead, a cis-acting regulatory region consisting of two duplicated 6-bp Male Gamete Selective Activation (MGSA) motifs occurs near the site of transcription initiation. Disruption of this sequence-specific site inactivates expression of a GFP reporter gene in sperm cells. Multiple copies of the MGSA motif fused with the minimal CaMV35S promoter elements confer reporter gene expression in sperm cells. Similar duplicated MGSA motifs are also identified from promoter sequences of sperm cell-expressed genes in Arabidopsis, suggesting selective activation is possibly a common mechanism for regulation of gene expression in sperm cells of flowering plants.

The GmFWL1 (FW2-2-like) nodulation gene encodes a plasma membrane microdomain-associated protein.

The soybean gene GmFWL1 (FW2-2-like1) belongs to a plant-specific family that includes the tomato FW2-2 and the maize CNR1 genes, two regulators of plant development. In soybean, GmFWL1 is specifically expressed in root hair cells in response to rhizobia and in nodules. Silencing of GmFWL1 expression significantly reduced nodule numbers supporting its role during soybean nodulation. While the biological role of GmFWL1 has been described, its molecular function and, more generally, the molecular function of plant FW2-2-like proteins is unknown. In this study, we characterized the role of GmFWL1 as a membrane microdomain-associated protein. Specifically, using biochemical, molecular and cellular methods, our data show that GmFWL1 interacts with various proteins associated with membrane microdomains such as remorin, prohibitins and flotillins. Additionally, comparative genomics revealed that GmFWL1 interacts with GmFLOT2/4 (FLOTILLIN2/4), the soybean ortholog to Medicago truncatula FLOTILLIN4, a major regulator of the M. truncatula nodulation process. We also observed that, similarly to MtFLOT4 and GmFLOT2/4, GmFWL1 was localized at the tip of the soybean root hair cells in response to rhizobial inoculation supporting the early function of GmFWL1 in the rhizobium infection process.

Pilot Study of a New Nonradioactive Surgical Guidance Technology for Locating Nonpalpable Breast Lesions.

BACKGROUND: The current technique for locating nonpalpable breast lesions is wire localization (WL). Radioactive seed localization and intraoperative ultrasound were developed to improve difficulties with WL. The SAVI SCOUT surgical guidance system was developed to improve these methods. The SCOUT system is a non-radioactive, FDA-cleared medical device that uses electromagnetic wave technology to provide real-time guidance during excisional breast procedures. METHODS: Consenting patients underwent localization and excision using an implantable electromagnetic wave reflective device (reflector) and a detector handpiece with a console. Using image guidance, the reflector was placed up to 7 days before the surgical procedure. The primary end points of the study were successful reflector placement, localization, and retrieval. The secondary end points were percentage of clear margins, reexcision rates, days of placement before excision, and physician comparison with WL. RESULTS: This study analyzed 50 patients. The reflectors were placed under mammographic guidance (n = 18, 36 %) or ultrasound guidance (n = 32, 64 %). Of the 50 patients, 10 (20 %) underwent excisional biopsy and 40 (80 %) had a lumpectomy. The lesion and reflector were successfully removed in all 50 patients, and no adverse events occurred. Of the 41 patients who had in situ and/or invasive carcinoma identified, 38 (93 %) had clear margins and 3 (7 %) were recommended for reexcision. CONCLUSIONS: These data suggest that the SCOUT system is safe and effective for guiding the excision of nonpalpable breast lesions and a viable alternative to standard localization options. A larger prospective, multi-institution trial of SCOUT currently is underway to validate these findings.

A Prospective, Single Arm, Multi-site, Clinical Evaluation of a Nonradioactive Surgical Guidance Technology for the Location of Nonpalpable Breast Lesions during Excision.

OBJECTIVES: This study was a multicenter evaluation of the SAVI SCOUT(®) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. METHODS: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(®) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(®) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. RESULTS: SCOUT(®) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. CONCLUSIONS: SCOUT(®) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

The Atlanta Motor Speech Disorders Corpus: Motivation, Development, and Utility.

BACKGROUND/AIMS: This paper describes the design and collection of a comprehensive spoken language dataset from speakers with motor speech disorders in Atlanta, Ga., USA. This collaborative project aimed to gather a spoken database consisting of nonmainstream American English speakers residing in the Southeastern US in order to provide a more diverse perspective of motor speech disorders. METHODS: Ninety-nine adults with an acquired neurogenic disorder resulting in a motor speech disorder were recruited. Stimuli include isolated vowels, single words, sentences with contrastive focus, sentences with emotional content and prosody, sentences with acoustic and perceptual sensitivity to motor speech disorders, as well as 'The Caterpillar' and 'The Grandfather' passages. RESULTS: Utility of this data in understanding the potential interplay of dialect and dysarthria was demonstrated with a subset of the speech samples existing in the database. CONCLUSION: The Atlanta Motor Speech Disorders Corpus will enrich our understanding of motor speech disorders through the examination of speech from a diverse group of speakers.

rpoS-Regulated core genes involved in the competitive fitness of Salmonella enterica Serovar Kentucky in the intestines of chickens.

Salmonella enterica serovar Kentucky has become the most frequently isolated serovar from poultry in the United States over the past decade. Despite its prevalence in poultry, it causes few human illnesses in the United States. The dominance of S. Kentucky in poultry does not appear to be due to single introduction of a clonal strain, and its reduced virulence appears to correlate with the absence of virulence genes grvA, sseI, sopE, and sodC1. S. Kentucky's prevalence in poultry is possibly attributable to its metabolic adaptation to the chicken cecum. While there were no difference in the growth rate of S. Kentucky and S. Typhimurium grown microaerophilically in cecal contents, S. Kentucky persisted longer when chickens were coinfected with S. Typhimurium. The in vivo advantage that S. Kentucky has over S. Typhimurium appears to be due to differential regulation of core Salmonella genes via the stationary-phase sigma factor rpoS. Microarray analysis of Salmonella grown in cecal contents in vitro identified several metabolic genes and motility and adherence genes that are differentially activated in S. Kentucky. The contributions of four of these operons (mgl, prp, nar, and csg) to Salmonella colonization in chickens were assessed. Deletion of mgl and csg reduced S. Kentucky persistence in competition studies in chickens infected with wild-type or mutant strains. Subtle mutations affecting differential regulation of core Salmonella genes appear to be important in Salmonella's adaptation to its animal host and especially for S. Kentucky's emergence as the dominant serovar in poultry.

Health care systems redesign project to improve dysphagia screening.

The purpose of this project was to improve dysphagia-screening processes in a tertiary Veterans Affairs Medical Center. The dysphagia-screening tool was redesigned on the basis of frontline clinician feedback, clinical guidelines, user satisfaction, and multidisciplinary expertise. The revised tool triggered a speech-language consult for positive screens and demonstrated higher scores in user satisfaction and task efficiency. Systems redesign processes were effective for redesigning the tool and implementing practice changes with clinicians involved in dysphagia screening.

Near infrared reflectance spectroscopy (NIRS) analyses of nutrient composition and condensed tannin concentrations in carolina willow (Salix caroliniana).

Iron overload disorder has been described in a number of zoo-managed species, and it has been recommended to increase the tannin composition of the diet as a safe way to minimize iron absorption in these iron-sensitive species. The goal of this study was to examine the potential of near infrared reflectance spectroscopy (NIRS) as a rapid and simple screening tool to assess willow (Salix caroliniana) nutrient composition (crude protein: CP; acid detergent fiber: ADF; neutral detergent fiber: NDF; lignin, gross energy: GE) and condensed tannin (CT) concentrations. Calibration equations were developed by regression of the lab values from 2 years using partial least squares on n = 144 NIRS spectra to predict n = 20 independent validation samples. Using the full 2-year dataset, good prediction statistics were obtained for CP, ADF, NDF, and GE in plant leaves and stems (r(2 ) > 0.75). NIRS did not predict lignin concentrations reliably (leaves r(2) = 0.52, stems r(2) = 0.33); however, CTs were predicted moderately well (leaves r(2) = 0.72, stems r(2) = 0.67). These data indicate that NIRS can be used to quantify several key nutrients in willow leaves and stems including concentrations of plant secondary compounds which, depending on the bioactivity of the compound, may be targeted to feed iron-sensitive browsing animals.

Transcriptomes of isolated Oryza sativa gametes characterized by deep sequencing: evidence for distinct sex-dependent chromatin and epigenetic states before fertilization.

The formation of a zygote by the fusion of egg and sperm involves the two gametic transcriptomes. In flowering plants, the embryo sac embedded within the ovule contains the egg cell, whereas the pollen grain contains two sperm cells inside a supporting vegetative cell. The difficulties of collecting isolated gametes and consequent low recovery of RNA have restricted in-depth analysis of gametic transcriptomes in flowering plants. We isolated living egg cells, sperm cells and pollen vegetative cells from Oryza sativa (rice), and identified transcripts for approximately 36 000 genes by deep sequencing. The three transcriptomes are highly divergent, with about three-quarters of those genes differentially expressed in the different cell types. Distinctive expression profiles were observed for genes involved in chromatin conformation, including an unexpected expression in the sperm cell of genes associated with active chromatin. Furthermore, both the sperm cell and the pollen vegetative cell were deficient in expression of key RNAi components. Differences in gene expression were also observed for genes for hormonal signaling and cell cycle regulation. The egg cell and sperm cell transcriptomes reveal major differences in gene expression to be resolved in the zygote, including pathways affecting chromatin configuration, hormones and cell cycle. The sex-specific differences in the expression of RNAi components suggest that epigenetic silencing in the zygote might act predominantly through female-dependent pathways. More generally, this study provides a detailed gene expression landscape for flowering plant gametes, enabling the identification of specific gametic functions, and their contributions to zygote and seed development.

A genome-wide survey of imprinted genes in rice seeds reveals imprinting primarily occurs in the endosperm.

Genomic imprinting causes the expression of an allele depending on its parental origin. In plants, most imprinted genes have been identified in Arabidopsis endosperm, a transient structure consumed by the embryo during seed formation. We identified imprinted genes in rice seed where both the endosperm and embryo are present at seed maturity. RNA was extracted from embryos and endosperm of seeds obtained from reciprocal crosses between two subspecies Nipponbare (Japonica rice) and 93-11 (Indica rice). Sequenced reads from cDNA libraries were aligned to their respective parental genomes using single-nucleotide polymorphisms (SNPs). Reads across SNPs enabled derivation of parental expression bias ratios. A continuum of parental expression bias states was observed. Statistical analyses indicated 262 candidate imprinted loci in the endosperm and three in the embryo (168 genic and 97 non-genic). Fifty-six of the 67 loci investigated were confirmed to be imprinted in the seed. Imprinted loci are not clustered in the rice genome as found in mammals. All of these imprinted loci were expressed in the endosperm, and one of these was also imprinted in the embryo, confirming that in both rice and Arabidopsis imprinted expression is primarily confined to the endosperm. Some rice imprinted genes were also expressed in vegetative tissues, indicating that they have additional roles in plant growth. Comparison of candidate imprinted genes found in rice with imprinted candidate loci obtained from genome-wide surveys of imprinted genes in Arabidopsis to date shows a low degree of conservation, suggesting that imprinting has evolved independently in eudicots and monocots.

Performance of single-use and multiuse diamond rotary cutting instruments with turbine and electric handpieces.

STATEMENT OF PROBLEM: As single-use rotary cutting instruments and electric handpieces become more available, the performance of these instruments with electric as compared to turbine handpieces requires evaluation. In addition, if rotary cutting instruments marketed as single-use instruments are used for multiple patients, the effects on their performance of cleaning, sterilization, and repeated use are of interest to the clinician. PURPOSE: The purpose of the study was to evaluate how the cleaning, autoclaving, and repeated use of single-use and multiuse rotary cutting instruments, with either a turbine or electric handpiece, affected their performance. MATERIAL AND METHODS: The effects on cutting performance of 2 handpieces (turbine and electric), 2 cleaning and sterilization conditions (cleaned and autoclaved versus noncleaned and nonautoclaved), and 6 different diamond rotary cutting instruments (4 single-use and 2 multiuse) during simulated tooth preparations were evaluated by using a 24-treatment condition full-factorial experimental design. A computer-controlled dedicated testing apparatus was used to simulate the cutting procedures, and machinable glass ceramic blocks were used as the cutting substrate for tangential cuts. In addition, for each treatment condition, 8 consecutive cuts, for a total of 192 cuts, were measured to assess the durability of the rotary cutting instruments. A linear mixed model was used to study the effect of instrument type, handpiece, cleaning, and sterilization, as well as the status and number of cuts on the outcome variables. The Tukey honestly significant difference test was used for the post hoc pairwise comparisons (α=.05). RESULTS: Performance, as measured by the rate of advancement, decreased with the repeated use of rotary cutting instruments (P<.001), while cleaning and sterilization procedures improved the average performance of the 8 cuts (P=.002). The electric handpiece showed a greater load than the turbine (P<.001) and a lower rate/load metric, but no differences in the rate of advancement. Significant differences were also detected among the different rotary cutting instruments tested with the Two Striper, which showed the highest cumulative performance of all groups. CONCLUSIONS: The repeated use of both single-use and multiuse rotary cutting instruments decreased cutting performance. The use of a cleaning and sterilization procedure between cuts improved the average cutting performance. During a tangential cutting process, although the ease of advancement (rate/load) was greater for the turbine, the electric handpiece did not produce a statistically different cutting rate.

Bringing platform trials closer to reality by enabling with digital research environment (DRE) connectivity.

Platform trials are generally regarded as an innovative approach to address clinical valuation of early stage candidates, regardless of modality as the evidence evolves. As a type of randomized clinical trial (RCT) design construct in which multiple interventions are evaluated concurrently against a common control group allowing new interventions to be added and the control group to be updated throughout the trial, they provide a dynamic and efficient mechanism to compare and potentially discriminate new treatment candidates. Their recent use in the evaluation of new therapies for COVID-19 has spurred new interest in the approach. The paucity of platform trials is less influenced by the novelty and operational requirements as opposed to concerns regarding the sharing of intellectual property (IP) and the lack of infrastructure to operationalize the conduct in the context of IP and data sharing. We provide a mechanism how this can be accomplished through the use of a digital research environment (DRE) providing a safe and secure platform for clinical researchers, quantitative and physician scientists to analyze and develop tools (e.g., models) on sensitive data with the confidence that the data and models developed are protected. A DRE, in this context, expands on the concept of a trusted research environment (TRE) by providing remote access to data alongside tools for analysis in a securely controlled workspace, while allowing data and tools to be findable, accessible, interoperable, and reusable (FAIR), version-controlled, and dynamically grow in size or quality as a result of each treatment evaluated in the trial.

Silica nanoparticles aid in structural leaf coloration in the Malaysian tropical rainforest understorey herb Mapania caudata.

BACKGROUND AND AIMS: Blue-green iridescence in the tropical rainforest understorey sedge Mapania caudata creates structural coloration in its leaves through a novel photonic mechanism. Known structures in plants producing iridescent blues consist of altered cellulose layering within cell walls and in special bodies, and thylakoid membranes in specialized plastids. This study was undertaken in order to determine the origin of leaf iridescence in this plant with particular attention to nano-scale components contributing to this coloration. METHODS: Adaxial walls of leaf epidermal cells were characterized using high-pressure-frozen freeze-substituted specimens, which retain their native dimensions during observations using transmission and scanning microscopy, accompanied by energy-dispersive X-ray spectroscopy to identify the role of biogenic silica in wall-based iridescence. Biogenic silica was experimentally removed using aqueous Na2CO3 and optical properties were compared using spectral reflectance. KEY RESULTS AND CONCLUSIONS: Blue iridescence is produced in the adaxial epidermal cell wall, which contains helicoid lamellae. The blue iridescence from cell surfaces is left-circularly polarized. The position of the silica granules is entrained by the helicoid microfibrillar layers, and granules accumulate at a uniform position within the helicoids, contributing to the structure that produces the blue iridescence, as part of the unit cell responsible for 2 ° Bragg scatter. Removal of silica from the walls eliminated the blue colour. Addition of silica nanoparticles on existing cellulosic lamellae is a novel mechanism for adding structural colour in organisms.