Federated Trusted Third Party as an Approach for Privacy Preserving Record Linkage in a Large Network of University Medicines in Pandemic Research

BackgroundThe Federal Ministry of Research and Education funded the Network of University Medicine for establishing an infrastructure for pandemic research. This includes the development of a COVID-19 Data Exchange Platform (CODEX) that provides standardised and harmonised data sets for COVID-19 research. Nearly all university hospitals in Germany are part of the project and transmit medical data from the local data integration centres to the CODEX platform. The medical data on a person that has been collected at several sites is to be made available on the CODEX platform in a merged form. To enable this, a federated trusted third party (fTTP) will be established, which will allow the pseudonymised merging of the medical data. The fTTP implements privacy preserving record linkage based on Bloom filters and assigns pseudonyms to enable re-pseudonymisation during data transfer to the CODEX platform.ResultsThe fTTP was implemented conceptually and technically. For this purpose, the processes that are necessary for data delivery were modelled. The resulting communication relationships were identified and corresponding interfaces were specified. These were developed according to the specifications in FHIR and validated with the help of external partners. Existing tools such as the identity management system E-PIX® were further developed accordingly so that sites can generate Bloom filters based on person identifying information. An extension for the comparison of Bloom filters was implemented for the federated trust third party. The correct implementation was shown in the form of a demonstrator and the connection of two data integration centres.ConclusionsThis article describes how the fTTP was modelled and implemented. In a first expansion stage, the fTTP was exemplarily connected through two sites and its functionality was demonstrated. Further expansion stages, which are already planned, have been technically specified and will be implemented in the future in order to also handle cases in which the privacy preserving record linkage achieves ambiguous results. The first expansion stage of the fTTP is available in the University Medicine network and will be connected by all participating sites in the ongoing test phase.

Modal Ventura Indonesia

Venture capital companies (PMV) not only provide financial financing but also participate in providing strategic direction to investee (PPU), thus providing solutions for PPU in carrying out company operations. This study uses a quantitative descriptive method related to PMV conditions in Indonesia for the 2015-2020 period. As a result, the number of PMVs showed a decreasing trend, but in contrast to the number of PPUs, PMV performance, assets, liabilities and equity showed an increasing trend during the study period. This indicates that PMV in Indonesia is able to grow and develop even though the number of PMV has decreased. It is hoped that PMV can increase the financing of shares and convertible bonds, so that PMV is able to bring micro, small and medium companies to successfully exit and enter the expansion stage either through mergers, acquisitions or IPOs in the capital market.

Research and Implementation of SCD Precision Decoupling in Intelligent Substation for Single Equipment Replacement

In the process of reconstruction and expansion of intelligent substation, it is difficult to accurately define the influence scope of SCD file upgrade. In the wake of each modification of SCD file, all configuration information contained in SCD needs to be re-verified, which greatly increases the workload of debugging, operation and maintenance of intelligent substation. Via decoupling SCD files, the problems of modification and re-verification of SCD files in the reconstruction and expansion stage can be tackled. In this paper, SCD precision decoupling method for smart substation with single equipment replacement is proposed, which makes SCD decoupling work more detailed, adaptable to various expansion and technical transformation of substation. The decoupling of SCD is refined from logical structure to physical link level, and the decoupling range of SCD is precisely determined, so as to minimize the modification and reverification range of SCD files and reduce the change risk caused by SCD modification.

The arrival and spread of the European firebug Pyrrhocoris apterus in Australia as documented by citizen scientists

We present evidence of the recent introduction and quick spread of the European firebug Pyrrhocoris apterus in Australia, as documented on the citizen science platform iNaturalist. The first public record of the species was reported in December 2018 in the City of Brimbank (Melbourne, Victoria). Since then, the species distribution has quickly expanded into 15 local government areas surrounding this first observation, including areas in both Metropolitan Melbourne and regional Victoria. The number of records of the European firebug in Victoria has also seen a substantial increase, with a current tally of almost 100 observations in iNaturalist as of July 31st, 2021. The case of the European firebug in Australia adds to the list of examples of citizen scientists playing a key role in not only early detection of newly introduced species but in documenting their expansion across their non-native range. Citizen science presents an exciting opportunity to complement biosecurity efforts carried out by government agencies, which often lack resources to sufficiently fund detection and monitoring programs given the overwhelming number of current and potential invasive species. Recognising and supporting the invaluable contribution of citizen scientists to science and society can help reduce this gap by: (1) increasing the number of introduced species that are quickly detected; (2) gathering evidence of the species’ early expansion stage; and (3) prompting adequate monitoring and rapid management plans for potentially harmful species.Given the range expansion patterns of the European firebug worldwide, their adaptation ability, and future climate scenarios, we suspect this species will continue expanding beyond Victoria, including other parts of Australia, New Zealand, and the South Pacific. We firmly believe that most of the knowledge about how this expansion process continues to happen will be provided by citizen scientists.

Biocontrol Agents Reduce Progression and Mycotoxin Production of Fusarium graminearum in Spikelets and Straws of Wheat

The aim of this study was to evaluate the interactions between wheat plant (spikelets and straws), a strain of mycotoxigenic pathogen Fusarium graminearum and commercial biocontrol agents (BCAs). The ability of BCAs to colonize plant tissue and inhibit the pathogen or its toxin production was observed throughout two phases of the life cycle of pathogens in natural conditions (colonization and survival). All evaluated BCAs showed effective reduction capacities of pathogenic traits. During establishment and the expansion stage, BCAs provoked an external growth reduction of F. graminearum (77–93% over the whole kinetic studied) and mycotoxin production (98–100% over the whole kinetic studied). Internal growth of pathogen was assessed with digital droplet polymerase chain reaction (ddPCR) and showed a very strong reduction in the colonization of the internal tissues of the spikelet due to the presence of BCAs (98% on average). During the survival stage, BCAs prevented the formation of conservation perithecia of the pathogen on wheat straw (between 88 and 98% of perithecia number reduction) and showed contrasting actions on the ascospores they contain, or perithecia production (−95% on average) during survival form. The mechanisms involved in these different interactions between F. graminearum and BCAs on plant matrices at different stages of the pathogen’s life cycle were based on a reduction of toxins, nutritional and/or spatial competition, or production of anti-microbial compounds.

Experimental study on blast damage of RC T-beam bridge

Purpose The purpose of this paper is to investigate the explosive performance and explosion damage mechanism of T-beam bridge structure. Design/methodology/approach On the basis of the existing specification, two T-beam bridge models were designed and fabricated. Test specimens of different explosive dosage and different blast height were carried out. The mechanical process, failure mode, blast damage model, damage identification mechanism and blast evolution law and quantitative evaluation were taken into account. Findings The results revealed that the web plate fracture failure is the key to the unstable failure of the whole T-beam bridge. The explosion failure phenomenon and blast damage evaluation criterion of RC T-beam bridge was divided into five stages: the original cracks stage of concrete material (D = 0 ∼ 0.1), the fractures initiation stage of concrete material (D = 0.1 ∼ 0.3), the stable expansion stage of cracks in concrete material (D = 0.3 ∼ 0.55), the unstable expansion stage of cracks in concrete material (D = 0.55 ∼ 0.8), the explosion fracture of steel bars and the overall instability and damage of the bridge (D = 0.8 ∼ 1.0), which can also be described as basically intact, slight damage, moderate damage, severe damage and collapsed. Social implications The research result will provide basis for the antiknock evaluation and damage repair technical specifications of the RC T-beam bridge. Originality/value The research results of damage evaluation serve as a basis for damage repair and reinforcement of bridge structures after explosion.

Study of Terpenoid Synthesis and Prenyltransferase in Roots of Rehmannia glutinosa Based on iTRAQ Quantitative Proteomics

Rehmannia glutinosa has important medicinal value; terpenoid is one of the main active components in R. glutinosa. In this study, iTRAQ technique was used to analyze the relative abundance of proteins in roots of R. glutinosa, and 6,752 reliable proteins were quantified. GO enrichment results indicated that most proteins were involved in metabolic process or cellular process, 57.63% proteins had catalytic activity, and 65.80% proteins were enriched in membrane-bounded organelle. In roots of R. glutinosa, there were 38 KEGG enrichments with significance, more DEPs were found in some pathways, especially the proteasome pathway and TCA cycle with 15.0% DEPs between elongation stage and expansion stage of roots. Furthermore, five KEGG pathways of terpenoid synthesis were found. Most prenyltransferases belong to FPP/GGPP synthase family, involved in terpenoid backbone biosynthesis, and all interacted with biotin carboxylase CAC2. Compared with that at the elongation stage, many prenyltransferases exhibited higher expression at the expansion stage or maturation stage of roots. In addition, eight FPP/GGPP synthase encoding genes were cloned from R. glutinosa, namely FPPS, FPPS1, GGPS, GGPS3, GGPS4, GGPS5, GPPS and GPPS2, introns were also found in FPPS, FPPS1, GGPS5 and GGPS2, and FPP/GPP synthases were more conservative in organisms, especially in viridiplantae, in which the co-occurrence of GPPS or GPPS2 was significantly higher in plants. Further analysis found that FPP/GGPP synthases of R. glutinosa were divided into three kinds, GGPS, GPPS and FPPS, and their gene expression was significantly diverse in different varieties, growth periods, or tissues of R. glutinosa. Compared with that of GGPS, the expression of GPPS and FPPS was much higher in R. glutinosa, especially at the expansion stage and maturation stage. Thus, the synthesis of terpenoids in roots of R. glutinosa is intricately regulated and needs to be further studied.

P–138 When is low quality really low? Should we transfer low-grade blastocysts?

Study question What is the live birth rate after single, low-grade blastocyst (LGB) transfer? Summary answer The live birth rate for LGBs is 28%, ranging between 15–31% for the different inner cell mass (ICM) and trophectoderm (TE) subgroups of LGBs. What is known already Live birth rates following LGB transfer are varied and have been reported to be in the range of 5–39%. However, these estimates are inaccurate as studies investigating live birth rates following LGB transfer are inherently limited by sample size (n = 10–440 for LGB transfers) due to LGBs being ranked last for transfer. Further, these studies are heterogenous with varied LGB definitions and design. Collating LGB live birth data from multiple clinics is warranted to obtain sufficient numbers of LGB transfers to establish reliable live birth rates, and to allow for delineation of different LGB subgroups, including blastocyst age and female age. Study design, size, duration We performed a multicentre, multinational retrospective cohort study in 9 IVF centres in China and New Zealand from 2012 to 2019. We studied the outcome of 6966 single blastocyst transfer cycles on days 5–7 (fresh and frozen) according to blastocyst grade, including 875 transfers from LGBs (<3bb, this being the threshold typically applied to LGB studies). Blastocysts with expansion stage 1 or 2 (early blastocysts) were excluded. Participants/materials, setting, methods The main outcome measured was live birth rate. Blastocysts were grouped according to quality grade: good-grade blastocysts (GGBs; n = 3849, aa, ab and ba), moderate-grade blastocysts (MGBs; n = 2242, bb) and LGBs (n = 875, ac, ca, bc, cb and cc) and live birth rates compared using the Pearson Chi-squared test. A logistic regression analysis explored the relationship between blastocyst grade and live birth after adjustment for the confounders: clinic, female age, expansion stage, and blastocyst age. Main results and the role of chance The live birth rates for GGBs, MGBs and LGBs were 45%, 36% and 28% respectively (p < 0.0001). Within the LGB group, the highest live birth rates were for grade c TE (30%) and the lowest were for grade c ICM (19%). The lowest combined grade (cc) maintained a 15% live birth rate (n = 7/48). After accounting for confounding factors, including female age and blastocyst characteristics, the odds of live birth were 2.33 (95% CI = 1.88–2.89) for GGBs compared to LGBs and 1.56 (95% CI = 1.28–1.92) for MGBs compared to LGBs following fresh and frozen blastocyst transfers (p < 0.0001, odds ratios confirmed in exclusively frozen blastocyst transfer cycles). When stratified by individual ICM and TE grade, the odds of live birth according to ICM grade were 1.31 (a versus b; 95% CI = 1.15–1.48), 2.82 (a versus c; 95% CI = 1.91–4.18) and 2.16 (b versus c; 95% CI = 1.48–3.16; all p < 0.0001). The odds of live birth according to TE grade were 1.33 (a versus b; 95% CI = 1.17–1.50, p < 0.0001), 1.85 (a versus c; 95% CI = 1.45–2.34, p < 0.0001) and 1.39 (b versus c; 95% CI = 1.12–1.73, p = 0.0024). Limitations, reasons for caution Despite the large multicentre design of the study, analyses of transfers occurring within the smallest subsets of the LGB group were limited by sample size. The study was not randomised and had a retrospective character. Wider implications of the findings: LGBs maintain satisfactory live birth rates (averaging 28%) in the general IVF population. Even those in the lowest grading tier maintain modest live birth rates (15%; cc). It is recommended that LGBs not be universally discarded, and instead considered for subsequent frozen embryo transfer to maximize cumulative live birth rates. Trial registration number Not applicable

Signal Intensity of Stem Diameter Variation for the Diagnosis of Drip Irrigation Water Deficit in Grapevine

Precise irrigation management of grapevines in greenhouses requires a reliable method to easily quantify and monitor the grapevine water status to enable effective manipulation of the water stress of the plants. This study describes a study on stem diameter variations of grapevine planted in a greenhouse in the semi-arid area of Northwest China. In order to determine the applicability of signal intensity of stem diameter variation to evaluate the water status of grapevine and soil. The results showed that the relative variation curve of the grapevine stem diameter from the vegetative stage to the fruit expansion stage showed an overall increasing trend. The correlations of MDS (maximum daily shrinkage) and DI (daily increase) with meteorological factors were significant (p < 0.05), and the correlations with SWP, RWC and soil moisture were weak. Although MDS and DI can diagnose grapevine water status in time, SIMDS and SIDI have the advantages of sensitivity and signal intensity compared with other indicators. Compared with MDS and DI, the R2 values of the regression equations of SIMDS and SIDI with SWP and RWC were high, and the correlation reached a very significant level (p < 0.01). Thus, SIMDS and SIDI are more suitable for the diagnosis of grapevine water status. The SIMDS peaked at the fruit expansion stage, reaching 0.957–1.384. The signal-to-noise ratio of SIDI was higher than that of MDS across the three treatments at the vegetative stage. The value and signal-to-noise ratio of SIDI at the flowering stage were similar to those of SIMDS, while the correlation between SIDI and the soil moisture content was higher than that of SIMDS. It can be concluded that that SIDI is suitable as an indicator of water status of grapevine and soil during the vegetative and flowering stages. In addition, the signal-to-noise ratio of SIMDS during the fruit expansion and mature stages was significantly higher than that of SIDI. Therefore, SIMDS is suitable as an indicator of the moisture status of grapevine and soil during the fruit expansion and mature stages. In general, SIMDS and SIDI were very good predictors of the plant water status during the growth stage and their continuous recording offers the promising possibility of their use in automatic irrigation scheduling in grapevine.

A phase Ib trial of belvarafenib in combination with cobimetinib in patients with advanced solid tumors: Interim results of dose-escalation and patients with NRAS-mutant melanoma of dose-expansion.

3007 Background: Belvarafenib, a potent, selective RAF dimer (type II) inhibitor, exhibits clinical activity in BRAFV600E- and NRAS-mutant (NRASm) melanoma patients. The combination of belvarafenib and cobimetinib more potently and durably suppressed MAPK pathway output and tumor growth than currently approved BRAF/MEK inhibitors in RAS- or RAF-mutant tumor xenograft models. This interim results of phase 1b trial evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of belvarafenib in combination with cobimetinib in dose-escalation and NRASm melanoma patients among the 9 indication-specific expansion cohorts. Methods: Patients with locally advanced or metastatic solid tumors harboring RAS or RAF mutation were enrolled in the dose-escalation stage, and the recommended doses were explored in the indication-specific expansion stage. Patients in the dose-escalation stage were given belvarafenib (100–300mg BID) in combination with cobimetinib (20–40mg QD) and the dose of subsequent cohorts was decided by a traditional 3+3 design and safety profile. Primary objectives were to evaluate the safety and tolerability, to estimate the maximum tolerable dose, and to identify the RP2D of the combination. Results: A total of 32 patients enrolled were evaluated for safety analysis; 19 were enrolled in 4 cohorts in the dose-escalation stage and 13 NRASm melanoma patients were enrolled in the indication-specific expansion stage (cut-off date: 2020-7-24). There were 3 DLTs (G3 colitis, G3 diarrhoea, G3 nausea) in 2 patients at the starting dose of belvarafenib 200mg BID continuously and cobimetinib 40mg QD 21/7 schedule. Belvarafenib dose was escalated to 300mg BID with cobimetinib 20mg QD, which did not result in DLTs. The most common treatment-emergent adverse events that occurred in ≥30% of 32 patients were dermatitis acneiform, diarrhoea, constipation, and increase in blood creatine phosphokinase. Two combination doses were explored in the indication-specific expansion stage. Out of the 9 indication-specific expansion cohorts, NRASm melanoma patients exhibited promising efficacy signal; 5 patients reached partial responses (PRs) out of 13, giving a response rate of 38.5%. Among them, 11 had been previously treated with checkpoint inhibitors (CPIs), including 5 (45.5%) who achieved PR. The median PFS was 7.3 months and 5 patients remained on the treatment at the cut-off date. Conclusions: Belvarafenib in combination with cobimetinib showed acceptable tolerability and encouraging efficacy in NRASm melanoma, and in those with prior CPI treatment. Further research is ongoing in other cohorts (Clinicaltrial.gov, NCT03284502) and in NRASm melanoma (reference GO42273 by clinicaltrials.gov ID number). *S.J.S and J.L contributed equally to this work. Clinical trial information: NCT03284502.