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In this work we discuss how femtoscopic analysis can shed light on the nature of the two lightest axial charmed mesons, denominated as $D_1(2430)$ and $D_1(2420)$, whose masses are similar but widths are different. Their properties are reasonably described taking into account meson-meson coupled channel dynamics and a bare quark-model pole constituting the lowest-order amplitudes. Two different bare quark-model states are used in order to accommodate the different scattering lengths coming from the lattice QCD calculations for the $D\pi$ and $D^*\pi$ systems and the data from the ALICE Collaboration on the $D\pi$ system. The amplitudes are employed as inputs to determine the correlation functions for the $D^{*}\pi$ and $D\rho$ channels and identify the signatures associated with the lowest-lying axial charmed mesons., Comment: 6 pages; 2 figures; Proceedings of The 10th International Conference on Quarks and Nuclear Physics, (QNP 2024) Jul 8-12, 2024, Barcelona, Spain

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.

Neuropsychiatric genome-wide association studies (GWASs), including those for autism spectrum disorder and schizophrenia, show strong enrichment for regulatory elements in the developing brain. However, prioritizing risk genes and mechanisms is challenging without a unified regulatory atlas. Across 672 diverse developing human brains, we identified 15,752 genes harboring gene, isoform, and/or splicing quantitative trait loci, mapping 3739 to cellular contexts. Gene expression heritability drops during development, likely reflecting both increasing cellular heterogeneity and the intrinsic properties of neuronal maturation. Isoform-level regulation, particularly in the second trimester, mediated the largest proportion of GWAS heritability. Through colocalization, we prioritized mechanisms for about 60% of GWAS loci across five disorders, exceeding adult brain findings. Finally, we contextualized results within gene and isoform coexpression networks, revealing the comprehensive landscape of transcriptome regulation in development and disease.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN1261900024113

A partire dalle ricerche di Michal Vojtáš e Gustavo Cavagnari, il contributo presenta una riflessione di taglio storico-pedagogico intorno al magistero salesiano sull’educazione affettiva dagli anni di don Bosco ai primi due decenni del nostro secolo. Il testo si sofferma sulla sfida storiografica affrontata dai due studiosi e poi offe alcuni spunti interpretativi circa alcune questioni decisive rispetto all’argomento in questione: la fedeltà al magistero della Chiesa e a don Bosco, i mutamenti socio-educativi e il problema antropologico.

The paper focuses on the design of a control strategy for safety-critical remote teleoperation. The main goal is to make the controlled system track the desired velocity specified by an operator while avoiding obstacles despite communication delays. Control Barrier Functions (CBFs) are used to define the safety constraints that the system has to respect to avoid obstacles, while Model Predictive Control (MPC) provides the framework for adjusting the desired input, taking the constraints into account. The resulting input is sent to the remote system, where appropriate low-level velocity controllers translate it into system-specific commands. The main novelty of the paper is a method to make the CBFs robust against the uncertainties caused by the network delays affecting the system's state and do so in a less conservative manner. The results show how the proposed method successfully solves the safety-critical teleoperation problem, making the controlled systems avoid obstacles with different types of network delay. The controller has also been tested in simulation and on a real manipulator, demonstrating its general applicability when reliable low-level velocity controllers are available., Comment: Accepted for publication in the 2024 European Control Conference (ECC)

Continuous maps representations, as opposed to traditional discrete ones such as grid maps, have been gaining traction in the research community. However, current approaches still suffer from high computation costs, making them unable to be used in large environments without sacrificing precision. In this paper, a scalable method building upon Gaussian Process-based Euclidean Distance Fields (GP-EDFs) is proposed. By leveraging structure inherent to indoor environments, namely walls and rooms, we achieve an accurate continuous map representation that is fast enough to be updated and used in real-time. This is possible thanks to a novel line-based room segmentation algorithm, enabling the creation of smaller local GP-EDFs for each room, which in turn also use line segments as its shape priors, thus representing the map more efficiently with fewer data points. We evaluate this method in simulation experiments, and make the code available open-source., Comment: Open-source code: https://github.com/EricssonResearch/Line-Based-Room-Segmentation-and-EDF

5G networks have the potential to provide external sensor data and offload computations for future industrial mobile robots. To enable these benefits while maintaining safety, we propose a modular architecture, including an onboard safety filter for the velocity control loop. The safety filter leverages robust control barrier functions to guarantee safety from collisions under bounded localization uncertainty. Initial experiments are performed to quantify the localization uncertainty and generate suitable bounds for the safety filter. We then derive the safety filter, and analyze its conservatism numerically. Finally, the method is demonstrated in experiments using an ABB Mobile YuMi® Research Platform robot., Part of ISBN: 979-8-3503-0124-3QC 20240228

BACKGROUND: Interrelated chronic vascular diseases (chronic kidney disease (CKD), type 2 diabetes (T2D) and cardiovascular disease (CVD)) are common with high morbidity and mortality. This study aimed to assess if an electronic-technology-based quality improvement intervention in primary care could improve detection and management of people with and at risk of these diseases. METHODS: Stepped-wedge trial with practices randomised to commence intervention in one of five 16-week periods. Intervention included (1) electronic-technology tool extracting data from general practice electronic medical records and generating graphs and lists for audit; (2) education regarding chronic disease and the electronic-technology tool; (3) assistance with quality improvement audit plan development, benchmarking, monitoring and support. De-identified data analysis using R 3.5.1 conducted using Bayesian generalised linear mixed model with practice and time-specific random intercepts. RESULTS: At baseline, eight included practices had 37,946 active patients (attending practice ≥3 times within 2 years) aged ≥18 years. Intervention was associated with increased OR (95% CI) for: kidney health checks (estimated glomerular filtration rate, urine albumin:creatinine ratio (uACR) and blood pressure) in those at risk 1.34 (1.26-1.42); coded diagnosis of CKD 1.18 (1.09-1.27); T2D diagnostic testing (fasting glucose or HbA1c) in those at risk 1.15 (1.08-1.23); uACR in patients with T2D 1.78 (1.56-2.05). Documented eye checks within recommended frequency in patients with T2D decreased 0.85 (0.77-0.96). There were no significant changes in other assessed variables. CONCLUSIONS: This electronic-technology-based intervention in primary care has potential to help translate guidelines into practice but requires further refining to achieve widespread improvements across the interrelated chronic vascular diseases.

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

Construction logistics is one of the essential functions in the modular construction industry due to the high demand for on-time delivery of components. For modular component suppliers, there is minimal flexibility in delivery times as generally, the installation times of modular components are critical to the contractor’s construction programme. There are several studies conducted in recent years that articulate novel methodologies in construction logistics scheduling; however, the industry still faces challenges in streamlining the whole supply chain to better cater to potential uncertainties that impact construction logistics. This paper looks at a case study on a modular component supplier in Melbourne, with regarding to the challenges faced and how they have effectively overcome these challenges and provides a framework to mitigate construction logistics related discrepancies in the supply chain. The resilience of these methods in facing unforeseen events such as COVID-19 will also be discussed. The overarching objectives of this paper are to include: (1) bibliographic mapping of related publications; (2) identification of current methods, problems and technologies used in modular construction logistics; and (3) propose best practice guidelines that can be implemented to effectively cater to such uncertainties in construction logistics to minimise the impact on the supply chain. Further, incorporating lean principles for planning construction logistics and transport for the modular construction industry is also in discussion. Finally, the potential future research directions are highlighted to guide the researchers to pursue areas of much importance.

Lean construction aims to improve efficiency through the reduction of wasteful activities. These waste reduction activities also indirectly improve the sustainability approach used by organizations. Our paper examines the definition of lean construction (LC), LC activities, and green construction as understood by academics through a focused literature review. It then examines these practices considering how these activities contribute towards enhancing the sustainability of the built environment and the organization. Our findings suggest that not all waste reduction activities have the same degree of effect on sustainability improvements. Some lean tools such as standardization and just-in-time (JIT) for production scheduling can have a better effect, especially, if the key performance indicators (KPI) specifically target sustainability indicators. “Lean and Green” is not a myth and is very much achievable in the construction industry with the current efforts towards industry 4.0/5.0. Combining these two concepts remains a challenge. This paper aims to learn from what we already know and suggests ways on how “Lean and Green” can be achieved in the future. The paper includes a discussion on leveraging lean and green concepts to achieve the sustainable development goals promoted by the United Nations.

Salah satu altermative bagi perusahaan untuk mendapatkan dana atau tambahan modal adalah melalui pasar modal, sebab melalui pasar modal investor dapat memperbanyak pilihan dalam menyalurkan dana dari investasi sesuai degan keinginannya, harga saham suatu perusaahan mencerminkan nilai perusahaan dimata masyarakat, apabila harga saham suatu perusahaan tinggi, maka nilai perusahaan dimata masyarakat juga baik dan begitu sebaliknya. Harga saham merupakan hal terpenting bagi perusahaan. Oleh sebab itu mereka perlu menilai kinerja suatu perusahaan melalui laporan keuangan perusahaan yang baik sangat berguna bagi investor, akan menanamkan modalnya, karena bisa dipastikan akan memperoleh keuntungan dari penanaman modal tersebut tersebut penelitian ini bertujuan untuk mengetahui pengaruh erning per shear, debt to equity ratio, net profit margin dan current rasio terhadap harga saham pada perusahaan otomotif yang terdaftar pada BEI priode 2017 – 2019. Dalam penelitian ini populasi yang dijadikan objek sampai saat ini adalah sejumlah 18 perusahaan otomotif yang terdaftar di bursa efek Indonesia (BEI) pada priode 2017 – 2019. Metode penarikan sample dilakukan dengan menggunakan laporan keuangan industri pada sektor otomotif yang terdaftar BEI yang berjumlah 6 perusahaan priode 2017 – 2019. Untuk menguji hipotesis yang ada maka digunakan teknik analisis regresi berganda. Model analisis ini dipilih karena penelitian ini dirancang untuk pengaruh keputusan kinerja keuangan terhadap harga saham. Hasil menyimpulkan bahwa: 1.) Erning per shear berpengaruh positif terhadap harga saham. 2.) Debt to equity ratio tidak berpengaruh terhadap harga saham. 3.) Net profit margin tidak berpengaruh terhadap harga saham. 4.) Curret ratio tidak berpengaruh terhadap harga saham.

Salah satu altermative bagi perusahaan untuk mendapatkan dana atau tambahan modal adalah melalui pasar modal, sebab melalui pasar modal investor dapat memperbanyak pilihan dalam menyalurkan dana dari investasi sesuai degan keinginannya, harga saham suatu perusaahan mencerminkan nilai perusahaan dimata masyarakat, apabila harga saham suatu perusahaan tinggi, maka nilai perusahaan dimata masyarakat juga baik dan begitu sebaliknya. Harga saham merupakan hal terpenting bagi perusahaan. Oleh sebab itu mereka perlu menilai kinerja suatu perusahaan melalui laporan keuangan perusahaan yang baik sangat berguna bagi investor, akan menanamkan modalnya, karena bisa dipastikan akan memperoleh keuntungan dari penanaman modal tersebut tersebut penelitian ini bertujuan untuk mengetahui pengaruh erning per shear, debt to equity ratio, net profit margin dan current rasio terhadap harga saham pada perusahaan otomotif yang terdaftar pada BEI priode 2017 – 2019. Dalam penelitian ini populasi yang dijadikan objek sampai saat ini adalah sejumlah 18 perusahaan otomotif yang terdaftar di bursa efek Indonesia (BEI) pada priode 2017 – 2019. Metode penarikan sample dilakukan dengan menggunakan laporan keuangan industri pada sektor otomotif yang terdaftar BEI yang berjumlah 6 perusahaan priode 2017 – 2019. Untuk menguji hipotesis yang ada maka digunakan teknik analisis regresi berganda. Model analisis ini dipilih karena penelitian ini dirancang untuk pengaruh keputusan kinerja keuangan terhadap harga saham. Hasil menyimpulkan bahwa: 1.) Erning per shear berpengaruh positif terhadap harga saham. 2.) Debt to equity ratio tidak berpengaruh terhadap harga saham. 3.) Net profit margin tidak berpengaruh terhadap harga saham. 4.) Curret ratio tidak berpengaruh terhadap harga saham.

Documentary climate data describe evidence of past climate arising from predominantly written historical documents such as diaries, chronicles, newspapers, or logbooks. Over the past decades, historians and climatologists have generated numerous document-based time series of local and regional climates. However, a global dataset of documentary climate time series has never been compiled, and documentary data are rarely used in large-scale climate reconstructions. Here, we present the first global multi-variable collection of documentary climate records. The dataset DOCU-CLIM comprises 621 time series (both published and hitherto unpublished) providing information on historical variations in temperature, precipitation, and wind regime. The series are evaluated by formulating proxy forward models (i.e., predicting the documentary observations from climate fields) in an overlapping period. Results show strong correlations, particularly for the temperature-sensitive series. Correlations are somewhat lower for precipitation-sensitive series. Overall, we ascribe considerable potential to documentary records as climate data, especially in regions and seasons not well represented by early instrumental data and palaeoclimate proxies.

There is a growing need for past weather and climate data to support science and decision-making. This paper describes the compilation and construction of a global multivariable (air temperature, pressure, precipitation sum, number of precipitation days) monthly instrumental climate database that encompasses a substantial body of the known early instrumental time series. The dataset contains series compiled from existing databases that start before 1890 (though continuing to the present) as well as a large amount of newly rescued data. All series underwent a quality control procedure and subdaily series were processed to monthly mean values. An inventory was compiled, and the collection was deduplicated based on coordinates and mutual correlations. The data are provided in a common format accompanied by the inventory. The collection totals 12452 meteorological records in 118 countries. The data can be used for climate reconstructions and analyses. It is the most comprehensive global monthly climate dataset for the preindustrial period so far.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. Methods: We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. Findings: We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). Interpretation: The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered – that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk st

Background: Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed. Research Question: What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA? Study Design and Methods: In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome. Results: We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85). Interpretation: Use of standard-dose epinephrine, high-dose epinephrine

We study the evolution of the doubly charmed state $T_{cc}^+$ in a hot hadron gas produced in the late stage of heavy-ion collisions. We use effective Lagrangians to calculate the thermally averaged cross sections of $T_{cc}^+$ production in reactions such as $ D^{(*)} D^{(*)} \rightarrow T_{cc}^+ \pi, T_{cc}^+ \rho $ and its absorption in the corresponding inverse processes. We then solve the rate equation to follow the time evolution of the $T_{cc}^+$ multiplicity, and determine how it is affected by the considered reactions during the expansion of the hadronic matter. We compare the evolution of the $T_{cc}^+$ abundance treated as a hadronic $S$-wave molecule and as a tetraquark state. Our results show that the tetraquark yield increases by a factor of about 2 at freeze-out, but it is still one order of magnitude smaller than the final yield of molecules formed from hadron coalescence. Also, the results indicate that $N_{T_{cc}}$ is more affected by interactions with hadronic medium than $ N_{X(3872)} $ in similar conditions. We also show that yields depend very weakly on the system size, represented by $\mathcal{N} = \left[ d N_{ch} / d \eta (\eta < 0.5)\right]^{1/3}$., Comment: 10 pages; 6 figures; v2: added a new Section (Section IV) with a comprehensive study of the influence of the system size, represented by the density of charged particles measured at midrapidity $\mathcal{N} = \left[ d N_{ch} / d \eta (\eta < 0.5)\right]$, on the results

We study the evolution of the doubly charmed state $T_{cc}^+$ in a hot hadron gas produced in the late stage of heavy-ion collisions. We use effective Lagrangians to calculate the thermally averaged cross sections of $T_{cc}^+$ production in reactions such as $ D^{(*)} D^{(*)} \rightarrow T_{cc}^+ \pi, T_{cc}^+ \rho $ and its absorption in the corresponding inverse processes. We then solve the rate equation to follow the time evolution of the $T_{cc}^+$ multiplicity, and determine how it is affected by the considered reactions during the expansion of the hadronic matter. We compare the evolution of the $T_{cc}^+$ abundance treated as a hadronic $S$-wave molecule and as a tetraquark state. Our results show that the tetraquark yield increases by a factor of about 2 at freeze-out, but it is still one order of magnitude smaller than the final yield of molecules formed from hadron coalescence. Also, the results indicate that $N_{T_{cc}}$ is more affected by interactions with hadronic medium than $ N_{X(3872)} $ in similar conditions. We also show that yields depend very weakly on the system size, represented by $\mathcal{N} = \left[ d N_{ch} / d \eta (\eta < 0.5)\right]^{1/3}$., Comment: 10 pages; 6 figures; v2: added a new Section (Section IV) with a comprehensive study of the influence of the system size, represented by the density of charged particles measured at midrapidity $\mathcal{N} = \left[ d N_{ch} / d \eta (\eta < 0.5)\right]$, on the results

Safety and risk-awareness are important properties for robotic systems, be it for protecting them from potentially dangerous internal states, or for avoiding collisions with obstacles and environmental hazards in disaster scenarios. Ensuring safety may be the role of more than one algorithmic layer in a system, each with varying assumptions and guarantees. This thesis investigates how to provide safety and risk-awareness in a robotic system by leveraging temporal logics, motion planning algorithms, and control theory. Traditional control theory approaches interpret the collision avoidance safety task as a `stay-away' task; obstacles are abstracted as collections of geometric shapes, and controllers are designed to avoid each shape individually. We propose interpreting the collision avoidance problem as a `stay-within' task: the obstacle-free space is abstracted into safe regions. We propose control laws based on Control Barrier functions that guarantee that the system remains within such safe regions throughout its mission. Our results demonstrate that our controller indirectly avoids obstacles while providing the system the freedom to move within the safe regions, without the necessity to plan and track a safe trajectory. Furthermore, by extending our idea with Metric Interval Temporal Logic, we are able to consider missions with explicit time bounds. Temporal logics are often used to define hard constraints on motion plans for robotic systems. However, some missions may require the system to violate constraints to make progress. Therefore, we propose to soften the hard constraints when necessary. Such soft constraints, here coined as spatial preferences, are used to account for relations between the system and the environment, such as distance from obstacles. The proposed minimally-violating motion planning algorithm attempts to find trajectories that satisfy the spatial preferences as much as possible, but violate them when needed. We demonstrate the use of spat, Säkerhet och riskmedvetenhet är viktiga egenskaper för robotsystem, oavsett om det är för att skydda dem från potentiellt farliga interna tillstånd eller för att undvika kollisioner med hinder och miljöfaror i katastrofscenarier. Att garantera säkerhete kan vara rollen för mer än ett lager av algoritmer i ett system, var och en med olika antaganden och garantier. Denna avhandling undersöker hur man skapar säkerhet och riskmedvetenhet i ett robotsystem genom att utnyttja tidslogik, algoritmer för rörelseplanering och reglerteori. Traditionella metoder inom reglerteori tolkar säkerhetsuppgiften för att undvika kollisioner som en `hålla-sig-utom-uppgift'; hinder abstraheras som samlingar av geometriska former, och regulatorer utformas för att undvika varje form individuellt. Vi föreslår att problemet med kollisionsundvikande tolkas som en `hålla-sig-inom-uppgift': utrymmet fritt från hinder abstraheras till säkra regioner. Vi föreslår regulatorer baserade på kontrollbarriärfunktioner som garanterar att systemet förblir inom sådana säkra regioner under hela sitt uppdrag. Våra resultat visar att vår regulator indirekt undviker hinder samtidigt som den ger systemet frihet att röra sig inom de säkra regionerna, utan att det är nödvändigt att planera och följa en viss säker bana. Genom att utöka vår idé med tidslogik med metriska intervall kan vi dessutom hantera uppdrag med explicita tidsgränser. Tidslogik används ofta för att definiera strikta begränsningar för rörelseplaner för robotsystem. Vissa uppdrag kan dock kräva att systemet bryter mot begränsningar för att göra framsteg. Därför föreslår vi att mjuka upp de strikta begränsningarna vid behov. Sådana följsamma begränsningar, här kallade för rumsliga preferenser, används för att redogöra för relationer mellan systemet och miljön, såsom avstånd från hinder. Den föreslagna minimalt regelbrytande algoritmen för rörelseplanering försöker hitta banor som uppfyller de rumsliga preferenserna så mycket som möjligt, men kränk, QC 20220117

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.

Safety and risk-awareness are important properties for robotic systems, be it for protecting them from potentially dangerous internal states, or for avoiding collisions with obstacles and environmental hazards in disaster scenarios. Ensuring safety may be the role of more than one algorithmic layer in a system, each with varying assumptions and guarantees. This thesis investigates how to provide safety and risk-awareness in a robotic system by leveraging temporal logics, motion planning algorithms, and control theory. Traditional control theory approaches interpret the collision avoidance safety task as a `stay-away' task; obstacles are abstracted as collections of geometric shapes, and controllers are designed to avoid each shape individually. We propose interpreting the collision avoidance problem as a `stay-within' task: the obstacle-free space is abstracted into safe regions. We propose control laws based on Control Barrier functions that guarantee that the system remains within such safe regions throughout its mission. Our results demonstrate that our controller indirectly avoids obstacles while providing the system the freedom to move within the safe regions, without the necessity to plan and track a safe trajectory. Furthermore, by extending our idea with Metric Interval Temporal Logic, we are able to consider missions with explicit time bounds. Temporal logics are often used to define hard constraints on motion plans for robotic systems. However, some missions may require the system to violate constraints to make progress. Therefore, we propose to soften the hard constraints when necessary. Such soft constraints, here coined as spatial preferences, are used to account for relations between the system and the environment, such as distance from obstacles. The proposed minimally-violating motion planning algorithm attempts to find trajectories that satisfy the spatial preferences as much as possible, but violate them when needed. We demonstrate the use of spat, Säkerhet och riskmedvetenhet är viktiga egenskaper för robotsystem, oavsett om det är för att skydda dem från potentiellt farliga interna tillstånd eller för att undvika kollisioner med hinder och miljöfaror i katastrofscenarier. Att garantera säkerhete kan vara rollen för mer än ett lager av algoritmer i ett system, var och en med olika antaganden och garantier. Denna avhandling undersöker hur man skapar säkerhet och riskmedvetenhet i ett robotsystem genom att utnyttja tidslogik, algoritmer för rörelseplanering och reglerteori. Traditionella metoder inom reglerteori tolkar säkerhetsuppgiften för att undvika kollisioner som en `hålla-sig-utom-uppgift'; hinder abstraheras som samlingar av geometriska former, och regulatorer utformas för att undvika varje form individuellt. Vi föreslår att problemet med kollisionsundvikande tolkas som en `hålla-sig-inom-uppgift': utrymmet fritt från hinder abstraheras till säkra regioner. Vi föreslår regulatorer baserade på kontrollbarriärfunktioner som garanterar att systemet förblir inom sådana säkra regioner under hela sitt uppdrag. Våra resultat visar att vår regulator indirekt undviker hinder samtidigt som den ger systemet frihet att röra sig inom de säkra regionerna, utan att det är nödvändigt att planera och följa en viss säker bana. Genom att utöka vår idé med tidslogik med metriska intervall kan vi dessutom hantera uppdrag med explicita tidsgränser. Tidslogik används ofta för att definiera strikta begränsningar för rörelseplaner för robotsystem. Vissa uppdrag kan dock kräva att systemet bryter mot begränsningar för att göra framsteg. Därför föreslår vi att mjuka upp de strikta begränsningarna vid behov. Sådana följsamma begränsningar, här kallade för rumsliga preferenser, används för att redogöra för relationer mellan systemet och miljön, såsom avstånd från hinder. Den föreslagna minimalt regelbrytande algoritmen för rörelseplanering försöker hitta banor som uppfyller de rumsliga preferenserna så mycket som möjligt, men kränk, QC 20220117

OBJECTIVE: To assess the outcomes of pregnancies at high-risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell-free DNA (cfDNA) screening. METHOD: A retrospective study of women who underwent cfDNA screening between September 2019 and July 2021 at three ultrasound services in Australia. Positive predictive values (PPVs) were calculated using fetal chromosomal analysis. RESULTS: Among 23,857 women screened, there were 93 high-risk results for RATs (0.39%) and 82 for SIs (0.34%). The PPVs were 3.8% (3/78, 95% CI 0.8%-10.8%) for RATs and 19.1% (13/68, 95% CI 10.6%-30.5%) for SIs. If fetuses with structural anomalies were also counted as true-positive cases, the PPV for RATS increased to 8.5% (7/82, 95% CI 3.5%-16.8%). Among 85 discordant cases with birth outcomes available (65.4%), discordant positive RATs had a significantly higher proportion of infants born below the 10th and 3rd birthweight percentiles than expected (19.6% (p = 0.022) and 9.8% (p = 0.004), respectively), which was not observed in the SI group (2.9% < 10th (p = 0.168) and 0.0% <3rd (p = 0.305)). CONCLUSION: The PPVs for SI and RAT results are low, except when a structural abnormality is also present. Discordant positive RATs are associated with growth restriction.

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.

Artificial Intelligence (AI) and its data-centric branch of machine learning (ML) have greatly evolved over the last few decades. However, as AI is used increasingly in real world use cases, the importance of the interpretability of and accessibility to AI systems have become major research areas. The lack of interpretability of ML based systems is a major hindrance to widespread adoption of these powerful algorithms. This is due to many reasons including ethical and regulatory concerns, which have resulted in poorer adoption of ML in some areas. The recent past has seen a surge in research on interpretable ML. Generally, designing a ML system requires good domain understanding combined with expert knowledge. New techniques are emerging to improve ML accessibility through automated model design. This paper provides a review of the work done to improve interpretability and accessibility of machine learning in the context of global problems while also being relevant to developing countries. We review work under multiple levels of interpretability including scientific and mathematical interpretation, statistical interpretation and partial semantic interpretation. This review includes applications in three areas, namely food processing, agriculture and health., Comment: published in the "Journal of the National Science Foundation of Sri Lanka, Volume 50"

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.

Safety and risk-awareness are important properties for robotic systems, be it for protecting them from potentially dangerous internal states, or for avoiding collisions with obstacles and environmental hazards in disaster scenarios. Ensuring safety may be the role of more than one algorithmic layer in a system, each with varying assumptions and guarantees. This thesis investigates how to provide safety and risk-awareness in a robotic system by leveraging temporal logics, motion planning algorithms, and control theory. Traditional control theory approaches interpret the collision avoidance safety task as a `stay-away' task; obstacles are abstracted as collections of geometric shapes, and controllers are designed to avoid each shape individually. We propose interpreting the collision avoidance problem as a `stay-within' task: the obstacle-free space is abstracted into safe regions. We propose control laws based on Control Barrier functions that guarantee that the system remains within such safe regions throughout its mission. Our results demonstrate that our controller indirectly avoids obstacles while providing the system the freedom to move within the safe regions, without the necessity to plan and track a safe trajectory. Furthermore, by extending our idea with Metric Interval Temporal Logic, we are able to consider missions with explicit time bounds. Temporal logics are often used to define hard constraints on motion plans for robotic systems. However, some missions may require the system to violate constraints to make progress. Therefore, we propose to soften the hard constraints when necessary. Such soft constraints, here coined as spatial preferences, are used to account for relations between the system and the environment, such as distance from obstacles. The proposed minimally-violating motion planning algorithm attempts to find trajectories that satisfy the spatial preferences as much as possible, but violate them when needed. We demonstrate the use of spat, Säkerhet och riskmedvetenhet är viktiga egenskaper för robotsystem, oavsett om det är för att skydda dem från potentiellt farliga interna tillstånd eller för att undvika kollisioner med hinder och miljöfaror i katastrofscenarier. Att garantera säkerhete kan vara rollen för mer än ett lager av algoritmer i ett system, var och en med olika antaganden och garantier. Denna avhandling undersöker hur man skapar säkerhet och riskmedvetenhet i ett robotsystem genom att utnyttja tidslogik, algoritmer för rörelseplanering och reglerteori. Traditionella metoder inom reglerteori tolkar säkerhetsuppgiften för att undvika kollisioner som en `hålla-sig-utom-uppgift'; hinder abstraheras som samlingar av geometriska former, och regulatorer utformas för att undvika varje form individuellt. Vi föreslår att problemet med kollisionsundvikande tolkas som en `hålla-sig-inom-uppgift': utrymmet fritt från hinder abstraheras till säkra regioner. Vi föreslår regulatorer baserade på kontrollbarriärfunktioner som garanterar att systemet förblir inom sådana säkra regioner under hela sitt uppdrag. Våra resultat visar att vår regulator indirekt undviker hinder samtidigt som den ger systemet frihet att röra sig inom de säkra regionerna, utan att det är nödvändigt att planera och följa en viss säker bana. Genom att utöka vår idé med tidslogik med metriska intervall kan vi dessutom hantera uppdrag med explicita tidsgränser. Tidslogik används ofta för att definiera strikta begränsningar för rörelseplaner för robotsystem. Vissa uppdrag kan dock kräva att systemet bryter mot begränsningar för att göra framsteg. Därför föreslår vi att mjuka upp de strikta begränsningarna vid behov. Sådana följsamma begränsningar, här kallade för rumsliga preferenser, används för att redogöra för relationer mellan systemet och miljön, såsom avstånd från hinder. Den föreslagna minimalt regelbrytande algoritmen för rörelseplanering försöker hitta banor som uppfyller de rumsliga preferenserna så mycket som möjligt, men kränk, QC 20220117

Underwater robotic arms are important devices that enables workers to carry out tasks remotely from a safe distance reducing or eliminating the risks that are involved with the task. The primary objective of the robotic manipulator is to perform maintenance and cleaning activities of the hull of a ship. However, the control of these devices underwater is quite complicated due to the numerous factors that make these systems unstable and non-linear. The aim of this study is to develop a multibody dynamic robotic manipulator model, integrated with a control strategy to optimize and obtain stable kinematics solutions. The hydrodynamic forces are integrated to the manipulator model considering buoyancy forces and surface drag forces. A basic algorithm is used to generate the joint angles using 7 geometrical parameters. The control of the manipulator was done to simply follow any path that represents the given coordinates. The P, I and D parameters are tuned individually to optimize the kinematic solution of the manipulator. 3-DOF articulated manipulator is the commonly used manipulator configuration. However, a 6-DOF manipulator configuration was selected in this study to allow for change in orientation using wrist motions.

Safety and risk-awareness are important properties for robotic systems, be it for protecting them from potentially dangerous internal states, or for avoiding collisions with obstacles and environmental hazards in disaster scenarios. Ensuring safety may be the role of more than one algorithmic layer in a system, each with varying assumptions and guarantees. This thesis investigates how to provide safety and risk-awareness in a robotic system by leveraging temporal logics, motion planning algorithms, and control theory. Traditional control theory approaches interpret the collision avoidance safety task as a `stay-away' task; obstacles are abstracted as collections of geometric shapes, and controllers are designed to avoid each shape individually. We propose interpreting the collision avoidance problem as a `stay-within' task: the obstacle-free space is abstracted into safe regions. We propose control laws based on Control Barrier functions that guarantee that the system remains within such safe regions throughout its mission. Our results demonstrate that our controller indirectly avoids obstacles while providing the system the freedom to move within the safe regions, without the necessity to plan and track a safe trajectory. Furthermore, by extending our idea with Metric Interval Temporal Logic, we are able to consider missions with explicit time bounds. Temporal logics are often used to define hard constraints on motion plans for robotic systems. However, some missions may require the system to violate constraints to make progress. Therefore, we propose to soften the hard constraints when necessary. Such soft constraints, here coined as spatial preferences, are used to account for relations between the system and the environment, such as distance from obstacles. The proposed minimally-violating motion planning algorithm attempts to find trajectories that satisfy the spatial preferences as much as possible, but violate them when needed. We demonstrate the use of spat, Säkerhet och riskmedvetenhet är viktiga egenskaper för robotsystem, oavsett om det är för att skydda dem från potentiellt farliga interna tillstånd eller för att undvika kollisioner med hinder och miljöfaror i katastrofscenarier. Att garantera säkerhete kan vara rollen för mer än ett lager av algoritmer i ett system, var och en med olika antaganden och garantier. Denna avhandling undersöker hur man skapar säkerhet och riskmedvetenhet i ett robotsystem genom att utnyttja tidslogik, algoritmer för rörelseplanering och reglerteori. Traditionella metoder inom reglerteori tolkar säkerhetsuppgiften för att undvika kollisioner som en `hålla-sig-utom-uppgift'; hinder abstraheras som samlingar av geometriska former, och regulatorer utformas för att undvika varje form individuellt. Vi föreslår att problemet med kollisionsundvikande tolkas som en `hålla-sig-inom-uppgift': utrymmet fritt från hinder abstraheras till säkra regioner. Vi föreslår regulatorer baserade på kontrollbarriärfunktioner som garanterar att systemet förblir inom sådana säkra regioner under hela sitt uppdrag. Våra resultat visar att vår regulator indirekt undviker hinder samtidigt som den ger systemet frihet att röra sig inom de säkra regionerna, utan att det är nödvändigt att planera och följa en viss säker bana. Genom att utöka vår idé med tidslogik med metriska intervall kan vi dessutom hantera uppdrag med explicita tidsgränser. Tidslogik används ofta för att definiera strikta begränsningar för rörelseplaner för robotsystem. Vissa uppdrag kan dock kräva att systemet bryter mot begränsningar för att göra framsteg. Därför föreslår vi att mjuka upp de strikta begränsningarna vid behov. Sådana följsamma begränsningar, här kallade för rumsliga preferenser, används för att redogöra för relationer mellan systemet och miljön, såsom avstånd från hinder. Den föreslagna minimalt regelbrytande algoritmen för rörelseplanering försöker hitta banor som uppfyller de rumsliga preferenserna så mycket som möjligt, men kränk, QC 20220117

Safety and risk-awareness are important properties for robotic systems, be it for protecting them from potentially dangerous internal states, or for avoiding collisions with obstacles and environmental hazards in disaster scenarios. Ensuring safety may be the role of more than one algorithmic layer in a system, each with varying assumptions and guarantees. This thesis investigates how to provide safety and risk-awareness in a robotic system by leveraging temporal logics, motion planning algorithms, and control theory. Traditional control theory approaches interpret the collision avoidance safety task as a `stay-away' task; obstacles are abstracted as collections of geometric shapes, and controllers are designed to avoid each shape individually. We propose interpreting the collision avoidance problem as a `stay-within' task: the obstacle-free space is abstracted into safe regions. We propose control laws based on Control Barrier functions that guarantee that the system remains within such safe regions throughout its mission. Our results demonstrate that our controller indirectly avoids obstacles while providing the system the freedom to move within the safe regions, without the necessity to plan and track a safe trajectory. Furthermore, by extending our idea with Metric Interval Temporal Logic, we are able to consider missions with explicit time bounds. Temporal logics are often used to define hard constraints on motion plans for robotic systems. However, some missions may require the system to violate constraints to make progress. Therefore, we propose to soften the hard constraints when necessary. Such soft constraints, here coined as spatial preferences, are used to account for relations between the system and the environment, such as distance from obstacles. The proposed minimally-violating motion planning algorithm attempts to find trajectories that satisfy the spatial preferences as much as possible, but violate them when needed. We demonstrate the use of spat, Säkerhet och riskmedvetenhet är viktiga egenskaper för robotsystem, oavsett om det är för att skydda dem från potentiellt farliga interna tillstånd eller för att undvika kollisioner med hinder och miljöfaror i katastrofscenarier. Att garantera säkerhete kan vara rollen för mer än ett lager av algoritmer i ett system, var och en med olika antaganden och garantier. Denna avhandling undersöker hur man skapar säkerhet och riskmedvetenhet i ett robotsystem genom att utnyttja tidslogik, algoritmer för rörelseplanering och reglerteori. Traditionella metoder inom reglerteori tolkar säkerhetsuppgiften för att undvika kollisioner som en `hålla-sig-utom-uppgift'; hinder abstraheras som samlingar av geometriska former, och regulatorer utformas för att undvika varje form individuellt. Vi föreslår att problemet med kollisionsundvikande tolkas som en `hålla-sig-inom-uppgift': utrymmet fritt från hinder abstraheras till säkra regioner. Vi föreslår regulatorer baserade på kontrollbarriärfunktioner som garanterar att systemet förblir inom sådana säkra regioner under hela sitt uppdrag. Våra resultat visar att vår regulator indirekt undviker hinder samtidigt som den ger systemet frihet att röra sig inom de säkra regionerna, utan att det är nödvändigt att planera och följa en viss säker bana. Genom att utöka vår idé med tidslogik med metriska intervall kan vi dessutom hantera uppdrag med explicita tidsgränser. Tidslogik används ofta för att definiera strikta begränsningar för rörelseplaner för robotsystem. Vissa uppdrag kan dock kräva att systemet bryter mot begränsningar för att göra framsteg. Därför föreslår vi att mjuka upp de strikta begränsningarna vid behov. Sådana följsamma begränsningar, här kallade för rumsliga preferenser, används för att redogöra för relationer mellan systemet och miljön, såsom avstånd från hinder. Den föreslagna minimalt regelbrytande algoritmen för rörelseplanering försöker hitta banor som uppfyller de rumsliga preferenserna så mycket som möjligt, men kränk, QC 20220117

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.

Objectives: To compare the traditional haematocrit-based criteria (>20% rise above baseline) with ultrasonography for diagnosing plasma leakage in dengue fever and to identify clinical indicators for triaging patients in resource-limited settings when the demand for ultrasonography is high. Methods: The Colombo Dengue Study is a prospective observational cohort study recruiting dengue patients in the first three days of dengue fever, before plasma leakage. Serial haematocrit assessments and ultrasonography were performed in patients recruited from October 2017 to February 2020. Clinical signs/symptoms and laboratory investigation results independently associated with ultrasound detected plasma leakage were identified with a derivation cohort and confirmed in a validation cohort. Results: 129 of 426 patients had ultrasonography-confirmed plasma leakage while 146 had a haematocrit rise >20%. Those positive on ultrasonography were also likely to fulfil the haematocrit-based criteria (OR: 4.42, 95% CI: 2.85–6.86), but the two groups did not overlap fully. In the derivation cohort (n = 317), platelet count <97 000/µl, AST/ALT > 51 IU/l and having abdominal pain in the first three days of fever were independent predictors of ultrasound-detected plasma leakage. In the validation cohort (n = 109), the combination of low platelet count and high aminotransferase level had better predictive capacity in terms of sensitivity and specificity. Conclusion: Dengue patients should be monitored with both serial haematocrit and ultrasonography whenever possible and plasma leakage should be diagnosed by either one of these criteria. If accessibility to scans is limited, platelet count, serum transaminase levels and presence of abdominal pain are useful to triage patients.

Background: Post-partum haemorrhage (PPH) occurs in up to 15% of births in Australia and remains the leading cause of maternal death globally. Simulation training for qualified interprofessional teams is linked to better health outcomes leading to improved patient safety. We explored the benefits of interprofessional simulation for undergraduate midwifery and medical students collaborating to manage a postpartum haemorrhage. This quantitative aspect of the research project focused specifically on the development of clinical knowledge, self-efficacy and satisfaction with simulation when caring for the deteriorating woman. Method(s): Ethical approval was received from the University HERC. A scenario of a woman having a primary postpartum haemorrhage immediately after birth was developed. Midwifery and medical students were required to work collaboratively to manage a simulation of the deteriorating woman. Participants were recruited from two courses, Bachelor of Nursing Bachelor of Midwifery and Bachelor of Medicine Bachelor of Surgery. Quantitative data were collected using self-reporting questionnaires over three repeated measures. Pre and post simulation questionnaires comprised two previously validated tools, Self-Efficacy Beliefs in Interprofessional Learning (SEBIL) and Satisfaction with Simulation Experience Survey (SSES). Purpose-developed multiple-choice questions measured students' clinical knowledge. Using IBM SPSS V25, data analysis included descriptive statistics, repeated Wilcox Signed Rank Test and chi-square. Statistical significance was set at alpha =.05. Result(s): 44 students with a median age of 21.5 years participated in eight simulations. 43 completed all phases. Differences were found between SEBIL sub-scales ('Interprofessional Interaction' and 'Interprofessional Team Evaluation and Feedback') and the SSES subscale 'Debrief and Reflection' pre and post simulation (p < 0.0001). There was no evidence of a difference in clinical knowledge. Student

Aim: To investigate the contribution of JUN in the inflammatory and fibrotic responses of renal tubular epithelial cells. Background(s): JUN is one component of the AP-1 transcription factor that transcribes genes in the inflammatory and fibrotic responses. Although not detected under homeostatic conditions, JUN is prominently expressed in tubules in both acute and chronic kidney injury; however, the precise role of JUN in kidney disease is unknown. Method(s): Mouse primary tubular epithelial cells were cultured using standard conditions. Cells were cultured for 4 days with 50nM of a locked nucleic acid anti-sense Jun oligonucleotide (LNA-JUN), or control oligonucleotide (LNA-Ctl). Cells were then stimulated with 10ng/mL tumour necrosis factor (TNF) for 6hr or with 5ng/mL transforming growth factor-b1 (TGF-b1) for 24hr and analysed by real-time polymerase chain reaction (RT-PCR). Cell proliferation was induced by 10ng/mL epidermal growth factor (EGF) for 48hr. Result(s): Cells treated with LNA-JUN showed a 3-fold knockdown of JUN protein levels by western blotting. TNF stimulation induced 15-fold and 10-fold increases in CCL-2 and IL-36A mRNA levels (markers of inflammation) in LNA-Ctl treated cells; this was reduced by 67% and 50% respectively, with LNA-JUN treatment (both p<0.0001). TGF-b1 stimulation of LNA-Ctl treated cells induced 2-fold and 2.3-fold increases in TGF-b1 and collagen IV mRNA levels (markers of fibrosis), respectively; this was reduced by 100% and 77% respectively in LNA-JUN treated cells (both p<0.001). By contrast, EGF-stimulation of epithelial cell proliferation was not affected by LNA-JUN treatment. Conclusion(s): JUN/AP1 plays a key role in the transcription of both pro-inflammatory and pro-fibrotic molecules in mouse tubular epithelial cells, without affected cell proliferation. These findings identify JUN as a potential therapeutic target in chronic kidney disease.

Aim: To investigate the contribution of JUN in the inflammatory and fibrotic responses of renal tubular epithelial cells. Background(s): JUN is one component of the AP-1 transcription factor that transcribes genes in the inflammatory and fibrotic responses. Although not detected under homeostatic conditions, JUN is prominently expressed in tubules in both acute and chronic kidney injury; however, the precise role of JUN in kidney disease is unknown. Method(s): Mouse primary tubular epithelial cells were cultured using standard conditions. Cells were cultured for 4 days with 50nM of a locked nucleic acid anti-sense Jun oligonucleotide (LNA-JUN), or control oligonucleotide (LNA-Ctl). Cells were then stimulated with 10ng/mL tumour necrosis factor (TNF) for 6hr or with 5ng/mL transforming growth factor-b1 (TGF-b1) for 24hr and analysed by real-time polymerase chain reaction (RT-PCR). Cell proliferation was induced by 10ng/mL epidermal growth factor (EGF) for 48hr. Result(s): Cells treated with LNA-JUN showed a 3-fold knockdown of JUN protein levels by western blotting. TNF stimulation induced 15-fold and 10-fold increases in CCL-2 and IL-36A mRNA levels (markers of inflammation) in LNA-Ctl treated cells; this was reduced by 67% and 50% respectively, with LNA-JUN treatment (both p<0.0001). TGF-b1 stimulation of LNA-Ctl treated cells induced 2-fold and 2.3-fold increases in TGF-b1 and collagen IV mRNA levels (markers of fibrosis), respectively; this was reduced by 100% and 77% respectively in LNA-JUN treated cells (both p<0.001). By contrast, EGF-stimulation of epithelial cell proliferation was not affected by LNA-JUN treatment. Conclusion(s): JUN/AP1 plays a key role in the transcription of both pro-inflammatory and pro-fibrotic molecules in mouse tubular epithelial cells, without affected cell proliferation. These findings identify JUN as a potential therapeutic target in chronic kidney disease.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org ). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

[EN] Electrocardiographic imaging (ECGI) is a technique to reconstruct non-invasively the electrical activity on the heart surface from body-surface potential recordings and geometric information of the torso and the heart. ECGI has shown scientific and clinical value when used to characterize and treat both atrial and ventricular arrhythmias. Regarding atrial fibrillation (AF), the characterization of the electrical propagation and the underlying substrate favoring AF is inherently more challenging than for ventricular arrhythmias, due to the progressive and heterogeneous nature of the disease and its manifestation, the small volume and wall thickness of the atria, and the relatively large role of microstructural abnormalities in AF. At the same time, ECGI has the advantage over other mapping technologies of allowing a global characterization of atrial electrical activity at every atrial beat and non-invasively. However, since ECGI is time-consuming and costly and the use of electrical mapping to guide AF ablation is still not fully established, the clinical value of ECGI for AF is still under assessment. Nonetheless, AF is known to be the manifestation of a complex interaction between electrical and structural abnormalities and therefore, true electro-anatomical-structural imaging may elucidate important key factors of AF development, progression, and treatment. Therefore, it is paramount to identify which clinical questions could be successfully addressed by ECGI when it comes to AF characterization and treatment, and which questions may be beyond its technical limitations. In this manuscript we review the questions that researchers have tried to address on the use of ECGI for AF characterization and treatment guidance (for example, localization of AF triggers and sustaining mechanisms), and we discuss the technological requirements and validation. We address experimental and clinical results, limitations, and future challenges for fruitful application of ECGI fo

[EN] Electrocardiographic imaging (ECGI) is a technique to reconstruct non-invasively the electrical activity on the heart surface from body-surface potential recordings and geometric information of the torso and the heart. ECGI has shown scientific and clinical value when used to characterize and treat both atrial and ventricular arrhythmias. Regarding atrial fibrillation (AF), the characterization of the electrical propagation and the underlying substrate favoring AF is inherently more challenging than for ventricular arrhythmias, due to the progressive and heterogeneous nature of the disease and its manifestation, the small volume and wall thickness of the atria, and the relatively large role of microstructural abnormalities in AF. At the same time, ECGI has the advantage over other mapping technologies of allowing a global characterization of atrial electrical activity at every atrial beat and non-invasively. However, since ECGI is time-consuming and costly and the use of electrical mapping to guide AF ablation is still not fully established, the clinical value of ECGI for AF is still under assessment. Nonetheless, AF is known to be the manifestation of a complex interaction between electrical and structural abnormalities and therefore, true electro-anatomical-structural imaging may elucidate important key factors of AF development, progression, and treatment. Therefore, it is paramount to identify which clinical questions could be successfully addressed by ECGI when it comes to AF characterization and treatment, and which questions may be beyond its technical limitations. In this manuscript we review the questions that researchers have tried to address on the use of ECGI for AF characterization and treatment guidance (for example, localization of AF triggers and sustaining mechanisms), and we discuss the technological requirements and validation. We address experimental and clinical results, limitations, and future challenges for fruitful application of ECGI fo

Objective: To determine the proportion of major fetal structural abnormalities that can be detected before 11 gestational weeks. Method(s): We conducted a retrospective study of individual patient files at a tertiary provider of obstetric and gynecological ultrasound in Melbourne, Australia. All women who had a pre-cell-free DNA ultrasound with a crown-rump length of less than 45 mm and had one or more ultrasounds at a later gestation were included in the analysis. The primary outcome was the incidence of a fetal structural abnormality. Result(s): A total of 3333 cases were included in the final analysis. Overall, 316 fetuses (9.5%) had a structural abnormality detected at any point throughout gestation, of which 86 were major structural abnormalities (2.6%). Sixteen fetal abnormalities were detected before 11 weeks of gestation, including 15 major abnormalities (17.4% of the major anomalies). All major fetal abnormalities detected before 11 gestational weeks were confirmed at later ultrasound examinations or the pregnancy did not continue (in four cases due to termination of pregnancy and in one case spontaneous miscarriage before first trimester morphology ultrasound). Conclusion(s): Detection of fetal abnormalities is possible before 11 weeks of gestation. Early suspicion is more likely in cases of major structural abnormalities.Copyright © 2021 John Wiley & Sons Ltd.

Background: Post-partum haemorrhage (PPH) occurs in up to 15% of births in Australia and remains the leading cause of maternal death globally. Simulation training for qualified interprofessional teams is linked to better health outcomes leading to improved patient safety. We explored the benefits of interprofessional simulation for undergraduate midwifery and medical students collaborating to manage a postpartum haemorrhage. This quantitative aspect of the research project focused specifically on the development of clinical knowledge, self-efficacy and satisfaction with simulation when caring for the deteriorating woman. Method(s): Ethical approval was received from the University HERC. A scenario of a woman having a primary postpartum haemorrhage immediately after birth was developed. Midwifery and medical students were required to work collaboratively to manage a simulation of the deteriorating woman. Participants were recruited from two courses, Bachelor of Nursing Bachelor of Midwifery and Bachelor of Medicine Bachelor of Surgery. Quantitative data were collected using self-reporting questionnaires over three repeated measures. Pre and post simulation questionnaires comprised two previously validated tools, Self-Efficacy Beliefs in Interprofessional Learning (SEBIL) and Satisfaction with Simulation Experience Survey (SSES). Purpose-developed multiple-choice questions measured students' clinical knowledge. Using IBM SPSS V25, data analysis included descriptive statistics, repeated Wilcox Signed Rank Test and chi-square. Statistical significance was set at alpha =.05. Result(s): 44 students with a median age of 21.5 years participated in eight simulations. 43 completed all phases. Differences were found between SEBIL sub-scales ('Interprofessional Interaction' and 'Interprofessional Team Evaluation and Feedback') and the SSES subscale 'Debrief and Reflection' pre and post simulation (p < 0.0001). There was no evidence of a difference in clinical knowledge. Student

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithi

OBJECTIVE: To determine the proportion of major fetal structural abnormalities that can be detected before 11 gestational weeks. METHODS: We conducted a retrospective study of individual patient files at a tertiary provider of obstetric and gynecological ultrasound in Melbourne, Australia. All women who had a pre-cell-free DNA ultrasound with a crown-rump length of less than 45 mm and had one or more ultrasounds at a later gestation were included in the analysis. The primary outcome was the incidence of a fetal structural abnormality. RESULTS: A total of 3333 cases were included in the final analysis. Overall, 316 fetuses (9.5%) had a structural abnormality detected at any point throughout gestation, of which 86 were major structural abnormalities (2.6%). Sixteen fetal abnormalities were detected before 11 weeks of gestation, including 15 major abnormalities (17.4% of the major anomalies). All major fetal abnormalities detected before 11 gestational weeks were confirmed at later ultrasound examinations or the pregnancy did not continue (in four cases due to termination of pregnancy and in one case spontaneous miscarriage before first trimester morphology ultrasound). CONCLUSION: Detection of fetal abnormalities is possible before 11 weeks of gestation. Early suspicion is more likely in cases of major structural abnormalities.

Recent trends envisage robots being deployed inareas deemed dangerous to humans, such as buildings with gasand radiation leaks. In such situations, the model of the underlying hazardous process might be unknown to the agent a priori, giving rise to the problem of planning for safe behaviour inpartially known environments. We employ Gaussian Process regression to create a probabilistic model of the hazardous process from local noisy samples. The result of this regression is then used by a risk metric, such as the Conditional Value-at-Risk, to reason about the safety at a certain state. The outcome is a risk function that can be employed in optimal motion planning problems. We demonstrate the use of the proposed function in two approaches. First is a sampling-based motion planning algorithm with an event-based trigger for online replanning. Second is an adaptation to the incremental Gaussian Process motion planner (iGPMP2), allowing it to quickly react and adapt to the environment. Both algorithms are evaluated in representative simulation scenarios, where they demonstrate the ability of avoiding high-risk areas., Not duplicate with DiVA 1661780QC 20220112

Recent trends envisage robots being deployed inareas deemed dangerous to humans, such as buildings with gasand radiation leaks. In such situations, the model of the underlying hazardous process might be unknown to the agent a priori, giving rise to the problem of planning for safe behaviour inpartially known environments. We employ Gaussian Process regression to create a probabilistic model of the hazardous process from local noisy samples. The result of this regression is then used by a risk metric, such as the Conditional Value-at-Risk, to reason about the safety at a certain state. The outcome is a risk function that can be employed in optimal motion planning problems. We demonstrate the use of the proposed function in two approaches. First is a sampling-based motion planning algorithm with an event-based trigger for online replanning. Second is an adaptation to the incremental Gaussian Process motion planner (iGPMP2), allowing it to quickly react and adapt to the environment. Both algorithms are evaluated in representative simulation scenarios, where they demonstrate the ability of avoiding high-risk areas., Not duplicate with DiVA 1661780QC 20220112

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.