All That Glitters Is Not Gold: Towards Process Discovery Techniques with Guarantees

The aim of a process discovery algorithm is to construct from event data a process model that describes the underlying, real-world process well. Intuitively, the better the quality of the event data, the better the quality of the model that is discovered. However, existing process discovery algorithms do not guarantee this relationship. We demonstrate this by using a range of quality measures for both event data and discovered process models. This paper is a call to the community of IS engineers to complement their process discovery algorithms with properties that relate qualities of their inputs to those of their outputs. To this end, we distinguish four incremental stages for the development of such algorithms, along with concrete guidelines for the formulation of relevant properties and experimental validation. We will also use these stages to reflect on the state of the art, which shows the need to move forward in our thinking about algorithmic process discovery.Comment: 13 pages, 4 figures. Submitted to the International Conference on Advanced Information Systems Engineering, 202

Timing and Nature of the Deepening of the Tasmanian Gateway

Tectonic changes that produced a deep Tasmanian Gateway between Australia and Antarctica are widely invoked as the major mechanism for Antarctic cryosphere growth and Antarctic Circumpolar Current (ACC) development during the Eocene/Oligocene (E/O) transition (∼34–33 Ma). Ocean Drilling Program (ODP) Leg 189 recovered near-continuous marine sedimentary records across the E/O transition interval at four sites around Tasmania. These records are largely barren of calcareous microfossils but contain a rich record of siliceous- and organic-walled marine microfossils. In this study we integrate micropaleontological, sedimentological, geochemical, and paleomagnetic data from Site 1172 (East Tasman Plateau) to identify four distinct phases (A–D) in the E/O Tasmanian Gateway deepening that are correlative among ODP Leg 189 sites. Phase A, prior to ∼35.5 Ma: minor initial deepening characterized by a shallow marine prodeltaic setting with initial condensation episodes. Phase B, ∼35.5–33.5 Ma: increased deepening marked by the onset of major glauconitic deposition and inception of energetic bottom-water currents. Phase C, ∼33.5–30.2 Ma: further deepening to bathyal depths, with episodic erosion by increasingly energetic bottom-water currents. Phase D, \u3c30.2 Ma: establishment of stable, open-ocean, warm-temperate, oligotrophic settings characterized by siliceous-carbonate ooze deposition. Our combined evidence indicates that this early Oligocene Tasmanian Gateway deepening initially produced an eastward flow of relatively warm surface waters from the Australo-Antarctic Gulf into the southwestern Pacific Ocean. This “proto-Leeuwin” current fundamentally differs from previous regional reconstructions of eastward flowing cool water (e.g., a “proto-ACC”) during the early Oligocene and thereby represents an important new constraint for reconstructing regional- to global-scale dynamics for this major global change event

A 26 million year gap in the central Arctic record at the greenhouse-icehouse transition: Looking for clues

The Cenozoic record of the Lomonosov Ridge (central Arctic Ocean) recovered during Integrated Ocean Drilling Program (IODP) Expedition 302 revealed an unexpected 26 Ma hiatus, separating middle Eocene (�44.4 Ma) from lower Miocene sediments (�18.2 Ma). To elucidate the nature of this unconformity, we performed a multiproxy palynological (dinoflagellate cysts, pollen, and spores), micropaleontological (siliceous microfossils), inorganic, and organic (Tetra Ether Index of lipids with 86 carbon atoms (TEX86) and Branched and Isoprenoid Tetraether (BIT)) geochemical analysis of the sediments from �5 m below to �7 m above the hiatus. Four main paleoenvironmental phases (A–D) are recognized in the sediments encompassing the unconformity, two below (A–B) and two above (C–D): (A) Below the hiatus, proxies show relatively warm temperatures, with Sea Surface Temperatures (TEX86-derived SSTs) of about 8�C and high fresh to brackish water influence. (B) Approaching the hiatus, proxies indicate a cooling trend (TEX86-derived SSTs of �5�C), increased freshwater influence, and progressive shoaling of the Lomonosov Ridge drilling site, located close to or at sea level. (C) The interval directly above the unconformity contains sparse reworked Cretaceous to Oligocene dinoflagellate cysts. Sediments were deposited in a relatively shallow, restricted marine environment. Proxies show the simultaneous influence of both fresh and marine waters, with alternating oxic and anoxic conditions. Pollen indicates a relatively cold climate. Intriguingly, TEX86-derived SSTs are unexpectedly high, �15–19�C. Such warm surface waters may be partially explained by the ingression of warmer North Atlantic waters after the opening of the Fram Strait during the early Miocene. (D) Sediments of the uppermost interval indicate a phase of extreme oxic conditions, and a well-ventilated environment, which occurred after the complete opening of the Fram Strait. Importantly, and in contrast with classical postrifting thermal subsidence models for passive margins, our data suggest that sediment erosion and/or nondeposition that generated the hiatus was likely due to a progressive shoaling of the Lomonosov Ridge. A shallow water setting both before and after the hiatus suggests that the Lomonosov Ridge remained at or near sea level for the duration of the gap in the sedimentary record. Interacting sea level changes and/or tectonic activity (possibly uplift) must be invoked as possible causes for such a long hiatus

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometnal scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between - 0.7% and 9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/11 I for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials

Optical Drug Monitoring: Photoacoustic Imaging of Nanosensors to Monitor Therapeutic Lithium in Vivo

Personalized medicine could revolutionize how primary care physicians treat chronic disease and how researchers study fundamental biological questions. To realize this goal, we need to develop more robust, modular tools and imaging approaches for in vivo monitoring of analytes. In this report, we demonstrate that synthetic nanosensors can measure physiologic parameters with photoacoustic contrast, and we apply that platform to continuously track lithium levels in vivo. Photoacoustic imaging achieves imaging depths that are unattainable with fluorescence or multiphoton microscopy. We validated the photoacoustic results that illustrate the superior imaging depth and quality of photoacoustic imaging with optical measurements. This powerful combination of techniques will unlock the ability to measure analyte changes in deep tissue and will open up photoacoustic imaging as a diagnostic tool for continuous physiological tracking of a wide range of analytes

One-pot RAFT and fast polymersomes assembly: a ‘beeline’ from monomers to drug-loaded nanovectors

Rapid and simple routes to functional polymersomes are increasingly needed to expand their clinical or industrial applications. Here we describe a novel strategy where polymersomes are prepared through an in-line process in just a few hours, starting from simple acrylate or acrylamide monomers. Using Perrier's protocol, well-defined amphiphilic diblock copolymers formed from PEG acrylate (mPEGA480), 2-(acryloyloxy)ethyl-3-chloro-4-hydroxybenzoate (ACH) or 2-(3-chloro-4-hydroxybenzamido)ethyl acrylate (CHB), have been synthesised by RAFT polymerisation in one-pot, pushing the monomer conversion for each block close to completion (≥94%). The reaction mixture, consisting of green biocompatible solvents (ethanol/water) have then been directly utilised to generate well-defined polymersomes, by simple cannulation into water or in a more automated process, by using a bespoke microfluidic device. Terbinafine and cyanocobalamine were used to demonstrate the suitability of the process to incorporate model hydrophobic and hydrophilic drugs, respectively. Vesicles size and morphology were characterised by DLS, TEM, and AFM. In this work we show that materials and experimental conditions can be chosen to allow facile and rapid generation drug-loaded polymersomes, through a suitable in-line process, directly from acrylate or acrylamide monomer building blocks

Chronostratigraphic Framework for the IODP Expedition 318 Cores from the Wilkes Land Margin: Constraints for Paleoceanographic Reconstruction

[1] The Integrated Ocean Drilling Program Expedition 318 to the Wilkes Land margin of Antarctica recovered a sedimentary succession ranging in age from lower Eocene to the Holocene. Excellent stratigraphic control is key to understanding the timing of paleoceanographic events through critical climate intervals. Drill sites recovered the lower and middle Eocene, nearly the entire Oligocene, the Miocene from about 17 Ma, the entire Pliocene and much of the Pleistocene. The paleomagnetic properties are generally suitable for magnetostratigraphic interpretation, with well‐behaved demagnetization diagrams, uniform distribution of declinations, and a clear separation into two inclination modes. Although the sequences were discontinuously recovered with many gaps due to coring, and there are hiatuses from sedimentary and tectonic processes, the magnetostratigraphic patterns are in general readily interpretable. Our interpretations are integrated with the diatom, radiolarian, calcareous nannofossils and dinoflagellate cyst (dinocyst) biostratigraphy. The magnetostratigraphy significantly improves the resolution of the chronostratigraphy, particularly in intervals with poor biostratigraphic control. However, Southern Ocean records with reliable magnetostratigraphies are notably scarce, and the data reported here provide an opportunity for improved calibration of the biostratigraphic records. In particular, we provide a rare magnetostratigraphic calibration for dinocyst biostratigraphy in the Paleogene and a substantially improved diatom calibration for the Pliocene. This paper presents the stratigraphic framework for future paleoceanographic proxy records which are being developed for the Wilkes Land margin cores. It further provides tight constraints on the duration of regional hiatuses inferred from seismic surveys of the region

Cumulative live birth rates in low-prognosis women

No external funds were obtained for the present study. The OPTIMIST study was funded by The Netherlands Organization for Health Research and Development (ZonMW number 171102020).Peer reviewedPublisher PD