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Research on themes related to green buildings is very important because it relates to building environmentally friendly buildings that prioritize sustainability. However, Green Building and Sustainable Development Goals (SDGs) research tends not to be comprehensive because it only relates to building construction and energy efficiency. For this reason, this research will discuss various things about green buildings and criticize what has been analyzed, whether it is still appropriate or not, considering current conditions that already use wireless and IoT technology. Through literature review techniques, this research examines themes related to the civil sector and the implementation of Green Building goals and SDGs. The Systematic Literature Review (SLR ) method is used. Namely, in-depth criticism and evaluation of previous research carried out systematically by applying applicable standards, using the Viosviewer and Publish and Perish applications. This method examines research results published in journals in a particular field. Literature reviews discuss previous research that meets SDGS objectives and is related to the civil sector. This research used 300 earlier studies with a research period ranging from 2010-2023 or 14 years. The research results show that the theme that is often raised is green materials and technology. The use of technology to measure building performance and energy efficiency is the most widely discussed theme. However, the analysis of Green Building and SDGs is rarely linked to IoT technology, saving water use, rainwater utilization, environmentally based wastewater management, and green building education, even though this is closely related to cost efficiency, energy efficiency, and speed, in communicating to achieve SDGs goals.

Abstract Background A predictive assay for late radiation toxicity would allow more personalized treatment planning, reducing the burden of toxicity for the more sensitive minority, and improving the therapeutic index for the majority. In a previous study in prostate cancer patients, the γ-H2AX foci decay ratio (γ-FDR) was the strongest predictor of late radiation toxicity. The current study aimed to validate this finding in a more varied group of patients with pelvic cancer. Additionally, the potential correlation between the γ-FDR and patient-reported outcomes was investigated. Methods Prostate and gynecological cancer patients with ≥ 24 months of follow-up were included in the current analysis. Toxicity was evaluated by physician (CTCAE version 4) and patient (EORTC questionnaires). γ-FDRs were determined in ex vivo irradiated lymphocytes. Correlation between γ-FDR and toxicity was assessed using both linear and logistic regression analyses. The highest toxicity grade recorded during follow-up was used. The association between global quality of life and γ-FDR was tested by comparing the change in quality of life over time in patients with γ-FDR

Objective: This single-centre retrospective study aims to determine the incidence of therapy-induced surgical benefit in patients with non-metastatic gastrointestinal stromal tumour (GIST) treated with neoadjuvant tyrosine kinase inhibitors (TKI) and evaluate whether this can be predicted by radiological response criteria. Methods: Thirty-nine non-metastatic GIST patients were treated with neoadjuvant TKI treatment, followed by curative-intended surgery, and monitored using contrast-enhanced computed tomography (CE-CT). Surgical benefit was independently assessed by two surgical oncologists and was defined by de-escalation of surgical strategy or reduced surgical complexity. Radiological response between baseline and the last preoperative scan was determined through RECIST 1.1, Choi and volumetric criteria. Results: In this patient cohort, median neoadjuvant treatment interval was 8.3 (IQR, 3.9–10.6) months. Surgical benefit was gained in 22/39 patients. When comparing radiological criteria to findings on surgical benefit, accuracy, sensitivity, and specificity for RECIST 1.1 (90 %, 100.0 % and 82 %), Choi (64 %, 24 %, and 96 %) and volumetry (95 %, 100.0 %, and 91 %) were calculated. In 30/39 patients, temporal changes in tumour size over the course of treatment was assessed. Tumour volume reduced significantly in the surgical-benefit group compared to the non-benefit group (72 % vs. 25 %, p

Background: Standardized consensus-based radiological reports for shoulder instability may improve clinical quality, reduce heterogeneity, and reduce workload. Therefore, the aim of this study was to determine important elements for the x-ray, magnetic resonance imaging (MRI) arthrography (MRA), and computed tomography (CT) report, the extent of variability, and important MRI views and settings. Methods: An expert panel of musculoskeletal radiologists and orthopedic surgeons was recruited in a three-round Delphi design. Important elements were identified for the x-ray, MRA, and CT report and important MRI views and setting. These were rated on a 0-9 Likert scale. High variability was defined as at least one score between 1-3 and 7-9. Consensus was reached when ≥80% scored an element 1-3 or 7-9. Results: The expert panel consisted of 21 musculoskeletal radiologists and 15 orthopedic surgeons. The number of elements identified in the first round was seventeen for the x-ray report, 52 for MRA, 21 for CT, and 23 for the MRI protocol. The number of elements that reached consensus was five for x-ray, twenty for MRA, nine for CT, and two for the MRI protocol. High variability was observed in 76.5% (n = 13) x-ray elements, 85.0% (n = 45) MRA, 76.2% (n = 16) CT, and 85.7% (n = 18) MRI protocol. Conclusion: Substantial variability was observed in the scoring of important elements in the radiological for the evaluation of anterior shoulder instability, regardless of modality. Consensus was reached for five elements in the x-ray report, twenty in the MRA report, and nine in the CT report. Finally, consensus was reached on two elements regarding MRA views and settings.

Objective To determine the efficacy of genicular artery embolisation (GAE) compared with sham GAE for pain reduction in patients with symptomatic mild-to-moderate knee osteoarthritis (KOA).Design Double-blind randomised sham-controlled clinical trial conducted from June 2019 to December 2021. The follow-up period was 4 months.Setting Single-centre study conducted at a university medical centre in Rotterdam, Netherlands.Participants 58 adults with symptomatic mild-to-moderate KOA not improving with conservative treatment.Interventions Participants were randomised to receive either GAE treatment or a sham GAE treatment.Main outcome measures The primary outcome was reduction of pain measured with the Knee Injury and Osteoarthritis Outcome Score pain subscale (0–100, with 0 representing the worst pain outcome and 100 the best) after 4 months. Outcomes were assessed at baseline and 1 and 4 months.Results From June 2019 to December 2021, 58 patients were included. 29 patients were randomised to the GAE group and 29 to the sham group. All participants completed the study. The mean pain reduction after 4 months was 21.4 (95% CI 13.9 to 28.8) for the GAE group and 18.4 points (95% CI 11.6 to 25.1) for the sham group. The between-group difference for the mean pain reduction was 3.0 (95% CI −7.1 to 13.0) with an estimated Cohen’s d effect size of d = 0.15 (95% CI −0.37 to 0.66). Group allocation was not a significant contributor to pain reduction (p = 0.31). No serious adverse events (AEs) occurred. 23 mild AEs occurred in the GAE group and 5 in the sham group.Conclusion We did not establish a clinical effect of GAE in patients with mild-to-moderate KOA as GAE produced a similar effect on pain reduction as a sham GAE procedure.Trial registration number NCT03884049.

Objective: It is difficult for health care providers to diagnose structural spinal osteoarthritis (OA), because current guidelines recommend against imaging in patients with back pain. Therefore, the aim of this study was to develop and internally validate multivariable diagnostic prediction models based on a set of clinical and demographic features to be used for the diagnosis of structural spinal OA on lumbar radiographs in older patients with back pain. Design: Three diagnostic prediction models, for structural spinal OA on lumbar radiographs (i.e. multilevel osteophytes, multilevel disc space narrowing (DSN), and both combined), were developed and internally validated in the ‘Back Complaints in Older Adults’ (BACE) cohort (N ​= ​669). Model performance (i.e. overall performance, discrimination and calibration) and clinical utility (i.e. decision curve analysis) were assessed. Internal validation was performed by bootstrapping. Results: Mean age of the cohort was 66.9 years (±7.6 years) and 59% were female. All three models included age, gender, back pain duration and duration of spinal morning stiffness as predictors. The combined model additionally included restricted lateral flexion and spinal morning stiffness severity, and exhibited the best model performance (optimism adjusted c-statistic 0.661; good calibration with intercept −0.030 and slope of 0.886) and acceptable clinical utility. The other models showed suboptimal discrimination, good calibration and acceptable decision curves. Conclusion: All three models for structural spinal OA displayed lesuboptimal discrimination and need improvement. However, these internally validated models have potential to inform primary care clinicians about a patient with risk of having structural spinal OA on lumbar radiographs. External validation before implementation in clinical care is recommended.

Objective: To determine the reliability and agreement of manual and automated morphological measurements, and agreement in morphological diagnoses. Methods: Thirty pelvic radiographs were randomly selected from the World COACH consortium. Manual and automated measurements of acetabular depth-width ratio (ADR), modified acetabular index (mAI), alpha angle (AA), Wiberg center edge angle (WCEA), lateral center edge angle (LCEA), extrusion index (EI), neck-shaft angle (NSA), and triangular index ratio (TIR) were performed. Bland-Altman plots and intraclass correlation coefficients (ICCs) were used to test reliability. Agreement in diagnosing acetabular dysplasia, pincer and cam morphology by manual and automated measurements was assessed using percentage agreement. Visualizations of all measurements were scored by a radiologist. Results: The Bland-Altman plots showed no to small mean differences between automated and manual measurements for all measurements except for ADR. Intraobserver ICCs of manual measurements ranged from 0.26 (95%-CI 0–0.57) for TIR to 0.95 (95%-CI 0.87–0.98) for LCEA. Interobserver ICCs of manual measurements ranged from 0.43 (95%-CI 0.10–0.68) for AA to 0.95 (95%-CI 0.86–0.98) for LCEA. Intermethod ICCs ranged from 0.46 (95%-CI 0.12–0.70) for AA to 0.89 (95%-CI 0.78–0.94) for LCEA. Radiographic diagnostic agreement ranged from 47% to 100% for the manual observers and 63%–96% for the automated method as assessed by the radiologist. Conclusion: The automated algorithm performed equally well compared to manual measurement by trained observers, attesting to its reliability and efficiency in rapidly computing morphological measurements. This validated method can aid clinical practice and accelerate hip osteoarthritis research.

Objective: No established definition for early-stage knee osteoarthritis (KOA) is available, nor classification criteria. Identifying the characteristics of individuals presenting with early-stage KOA symptoms can enhance diagnosis to prevent progression. This study aimed to describe clinical and structural features of individuals presenting with knee complaints within two years after their first consultation, while exploring differences in the duration of knee complaints. Method: Baseline data was used from the LITE randomized controlled trial, assessing the effectiveness of a lifestyle intervention for individuals with knee complaints and overweight in primary care. Baseline assessments included questionnaires, clinical assessment, and MRI of the most symptomatic knee. Differences between groups with varying durations of knee complaints (

Artificial Intelligence (AI) technology is increasingly being adopted in the construction industry in the current era. AI can be integrated with digital technologies such as Building Information Modeling (BIM), Internet of Things (IoT), and Smart Vision (SV). The integration of AI with digital technology has the potential to enhance efficiency, productivity, accuracy, and safety in construction project. This systematic literature review focuses on studying the implementation of AI in construction management, aiming to assess the current role of AI and anticipate future trends in the field. The findings of systematic literature review reveal that AI has been employed in construction projects for tasks such as estimation, resource management, improvement of workplace safety, material selection, structural analysis, and more. The advancements in digital technology, including the influence of 5G connectivity, have further augmented the sophistication of AI applications in the current era. The systematic literature review also delves into the study of machine learning and deep learning, both of which are pivotal in AI technology for executing predictive tasks, analyses, and automated decision-making. Despite the vast potential of AI, this review identifies various challenges associated with the technology, particularly concerning data security. Most existing studies focus on the limited application of AI in specific domains within the construction industry. To address this gap, this systematic literature review provides a comprehensive literature review on the broader perspective of AI application in construction management.

Abstract Objective To build and validate an early risk prediction model for gestational diabetes mellitus (GDM) based on first-trimester electronic medical records including maternal demographic and clinical risk factors. Methods To develop and validate a GDM prediction model, two datasets were used in this retrospective study. One included data of 14,015 pregnant women from Máxima Medical Center (MMC) in the Netherlands. The other was from an open-source database nuMoM2b including data of 10,038 nulliparous pregnant women, collected in the USA. Widely used maternal demographic and clinical risk factors were considered for modeling. A GDM prediction model based on elastic net logistic regression was trained from a subset of the MMC data. Internal validation was performed on the remaining MMC data to evaluate the model performance. For external validation, the prediction model was tested on an external test set from the nuMoM2b dataset. Results An area under the receiver-operating-characteristic curve (AUC) of 0.81 was achieved for early prediction of GDM on the MMC test data, comparable to the performance reported in previous studies. While the performance markedly decreased to an AUC of 0.69 when testing the MMC-based model on the external nuMoM2b test data, close to the performance trained and tested on the nuMoM2b dataset only (AUC = 0.70).

Abstrak Pekerjaan pembongkaran bangunan merupakan proses yang esensial dalam industri konstruksi untuk menghancurkan atau meruntuhkan struktur bangunan setelah masa manfaatnya berakhir. Proses ini melibatkan penggunaan peralatan khusus dan mematuhi prosedur hukum serta mendapatkan persetujuan pemerintah setempat. Penelitian ini menggunakan metode bibliometerik dengan menggunakan bantuan aplikasi Publish or Perish (Pop) dan VOSviewer. Dari hasil seleksi yang dilakukan dengan PoP dilakukan seleksi artikel-artikel yang relevan dan sesuai dengan penelitian yang dilakukan. Untuk mengetahui hubungan masing-masing kata kunci dalam artikel, maka diolah dengan menggunakan aplikasi VOSviewer dengan dilanjutkan seleksi lebih cermat dan teliti sehingga pembahasan tidak terlalu melebar. Artikel-artikel yang sudah dikumpulkan dijadikan bahan penitian schematic literature review ini. Tujuan dari Penelitian ini adalah untuk menjelaskan penererapan pekerjaan pembongkaran dengan beberapa metode yang masing-masing memiliki kelebihan dan kekurangannya. Selain pembahasan tentang pentingnya pekerjaan pembongkaran (demolishing) juga jelaskan terkait daur ulang dari limbah bongkaran konstruksi dan perkembangan-perkembangan yang telah dilakukan dalam pengolahan limbah hasil konstruksi dan bongkaran konstruksi. Kata kunci: pembongkaran, metode bongkaran, limbah bongkaran, daur ulang , Abstract Building demolition work is an essential process in the construction industry to destroy or demolish building structures after their useful life has ended. This process involves using special equipment and complying with legal procedures and obtaining local government approval. This research uses a bibliometric method using the Publish or Perish (PoP) and VOSviewer applications. From the results of the selection carried out with PoP, articles were selected that were relevant and in accordance with the research carried out. To find out the relationship between each keyword in the article, it is processed using the VOSviewer application, followed by more careful and thorough selection so that the discussion does not expand too much. The articles that have been collected are used as material for this schematic literature review. The aim of this research is to explain the application of demolition work using several methods, each of which has its advantages and disadvantages. Apart from discussing the importance of demolition work, it also explains the recycling of construction demolition waste and the developments that have been made in processing construction waste and construction demolition waste. Keywords: demolishing, demolishing methods, demolishing waste, recycling

Purpose: The recently released EANM/SNMMI guideline, endorsed by several important clinical and imaging societies in the field of breast cancer (BC) care (ACR, ESSO, ESTRO, EUSOBI/ESR, EUSOMA), emphasized the role of [18F]FDG PET/CT in management of patients with no special type (NST) BC. This review identifies and summarizes similarities, discrepancies and novelties of the EANM/SNMMI guideline compared to NCCN, ESMO and ABC recommendations. Methods: The EANM/SNMMI guideline was based on a systematic literature search and the AGREE tool. The level of evidence was determined according to NICE criteria, and 85 % agreement or higher was reached regarding each statement. Comparisons with NCCN, ESMO and ABC guidelines were examined for specific clinical scenarios in patients with early stage through advanced and metastatic BC. Results: Regarding initial staging of patients with NST BC, [18F]FDG PET/CT is the preferred modality in the EANM-SNMMI guideline, showing superiority as a single modality to a combination of contrast-enhanced CT of thorax-abdomen-pelvis plus bone scan in head-to-head comparisons and a randomized study. Its use is recommended in patients with clinical stage IIB or higher and may be useful in certain stage IIA cases of NST BC. In NCCN, ESMO, and ABC guidelines, [18F]FDG PET/CT is instead recommended as complementary to conventional imaging to solve inconclusive findings, although ESMO and ABC also suggest [18F]FDG PET/CT can replace conventional imaging for staging patients with high-risk and metastatic NST BC. During follow up, NCCN and ESMO only recommend diagnostic imaging if there is suspicion of recurrence. Similarly, EANM-SNMMI states that [18F]FDG PET/CT is useful to detect the site and extent of recurrence only when there is clinical or laboratory suspicion of recurrence, or when conventional imaging methods are equivocal. The EANM-SNMMI guideline is the first to emphasize a role of [18F]FDG PET/CT for assessing early metabolic response to primary systemic therapy, particularly for HER2+ BC and TNBC. In the metastatic setting, EANM-SNMMI state that [18F]FDG PET/CT may help evaluate bone metastases and determine early response to treatment, in agreement with guidelines from ESMO. Conclusions: The recently released EANM/SNMMI guideline reinforces the role of [18F]FDG PET/CT in the management of patients with NST BC supported by extensive evidence of its utility in several clinical scenarios.

We show that the first-order theory of Sturmian words over Presburger arithmetic is decidable. Using a general adder recognizing addition in Ostrowski numeration systems by Baranwal, Schaeffer and Shallit, we prove that the first-order expansions of Presburger arithmetic by a single Sturmian word are uniformly $\omega$-automatic, and then deduce the decidability of the theory of the class of such structures. Using an implementation of this decision algorithm called Pecan, we automatically reprove classical theorems about Sturmian words in seconds, and are able to obtain new results about antisquares and antipalindromes in characteristic Sturmian words.

IntroductionExtra-uterine life support technology could provide a more physiologic alternative for the treatment of extremely premature infants, as it allows further fetal growth and development ex utero. Animal studies have been carried out which involved placing fetuses in a liquid-filled incubator, with oxygen supplied through an oxygenator connected to the umbilical vessels. Hence, by delaying lung exposure to air, further lung development and maturation can take place. This medical intervention requires adjustments to current obstetric procedures to maintain liquid-filled lungs through a so-called transfer procedure.MethodsOur objective was to develop obstetric device prototypes that allow clinicians to simulate this birth procedure to safely transfer the infant from the mother's uterus to an extra-uterine life support system. To facilitate a user-centered design, implementation of medical simulation during early phase design of the prototype development was used. First, the requirements for the procedure and devices were established, by reviewing the literature and through interviewing direct stakeholders. The initial transfer device prototypes were tested on maternal and fetal manikins in participatory simulations with clinicians.Results & discussionThrough analysis of recordings of the simulations, the prototypes were evaluated on effectiveness, safety and usability with latent conditions being identified and improved. This medical simulation-based design process resulted in the development of a set of surgical prototypes and allowed for knowledge building on obstetric care in an extra-uterine life support context.

Introduction Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The Joining the Dots cohort study uses linked population data to understand the relationship between services, therapeutic interventions and outcomes of children with PDE.Methods and analysis Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0.Ethics and dissemination Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome.

Abstrak— Tujuan penelitian ini adalah untuk mengembangkan aplikasi ujian daring interaktif berbasis web. Adanya kebutuhan dari dosen dan mahasiswa dalam pembelajaran daring, dan untuk bisa menerapkan ujian daring yang bisa diakses melalui internet. Pengembangan aplikasi menggunakan model Waterfall. Perancangan menggunakan used cased, activity, dan data flow diagram. Koding aplikasi web menggunakan html, css, dan javascipt. Dari hasil implementasi pengembangan dan pengujian blackbox test dapat disimpulkan bahwa aplikasi ujian daring interaktif, sudah berhasil dibuat. Aplikasi ini memiliki dukungan hosting dan pemeliharaan dengan feedback dan update.

Given the significance of education in Chinese culture and based on the contextual model of parenting style (Darling & Steinberg, Psychological Bulletin, 113, 487-496, 1993 (See CR14)), the present study attempted to explain the association between parental expectations and students' educational expectations in Chinese families by testing the potential moderating role of the training parenting style, a parenting style that is based on Chinese culture. 281 Chinese adolescent-parent dyads, including early adolescents (49.5% girls, M.sub.age = 12.54) and one of their parents (70.5% mothers, M.sub.age = 40.91), completed two versions of a self-report survey questionnaire. Results indicated that parental expectations exerted influence on students' educational expectations with perceived parental expectations as a mediator. Moreover, training parenting style moderated the relationship between parental expectations and perceived parental expectations. High training parenting style buffered the effect of low parental expectations on perceived parental expectations. The interaction between parental expectations and training parenting style revealed a culturally specific mechanism that contributed to the transmission of educational expectations in Chinese families., Author(s): Ru-De Liu [sup.1] , Cai-Xia Shen [sup.2] , Yan Sun [sup.1] , Yi Ding [sup.3] , Xinchen Fu [sup.1] , Shuyang Jiang [sup.1] , Tian-Po Oei [sup.4] [sup.5] , [...]

Test anxiety theory is believed to increase distraction from task-irrelevant stimuli. However, it is unclear whether the test-anxious individuals will show distraction to the peripheral distractor. Load theory suggested that perceptual and cognitive loads could manipulate attentional demands during distractor processing. Besides, how increasing the perceptual and cognitive load will affect the distraction in test anxiety remains explored. The present research aimed to test these issues by combining the eye-tracking technique and letter discrimination task with varying types of the peripheral distractor in high-test anxious (HTA) vs. low-test anxious (LTA) individuals. Experiment 1 manipulated the perceptual load by adjusting the difficulty of the task, and Experiment 2 increased cognitive load by adding a backward counting task based on the procedure of Experiment 1. Consequently, HTA individuals had longer response times (RTs) in the test-related distractor condition than in the non-distractor condition of fast-response trials in both experiments, suggesting that the HTA group showed distraction to the test-related distractor within fast-response trials. Besides, the HTA group had fewer fixations than low test-anxious (LTA) individuals in Experiment 1, suggesting that the HTA group may keep hypervigilance by maintaining a broad distribution of attention. These results support that distraction in test anxiety is associated with unspecific hypervigilance and specific inhibition deficits., Author(s): Cenlou Hu [sup.1] , Tian Po Oei [sup.2] , Yan Hong [sup.3] , Renlai Zhou [sup.1] [sup.3] [sup.4] Author Affiliations: (1) grid.263826.b, 0000 0004 1761 0489, Key Laboratory of [...]

Currently, the cafe is a place to relieve stress through a healing concept in its interior design. So, the cafe design must be as comfortable as possible to meet the concept goals. This research aims to determine user perception of the healing environment in a cafe environment based on three aspects (the five basic senses, user psychology, and indoor and outdoor natural elements) and was conducted using quantitative research methodology. Data retrieval was carried out through Google Forms media using closed-ended questions. The results proved that three aspects of the healing environment, including sensory, psychological, and natural aspects described in lighting, color tone selection, air, a good level of privacy, and the presence of plants, could help the healing process. If there is one aspect that is lacking, then visitors cannot feel healing. If a café wants to create a healing environment, then the three aspects (senses, psychological, and natural) must be fulfilled.

Abstract Background Type 2 diabetes (T2D) is a heterogeneous and polygenic disease. Previous studies have leveraged the highly polygenic and pleiotropic nature of T2D variants to partition the heterogeneity of T2D, in order to stratify patient risk and gain mechanistic insight. We expanded on these approaches by performing colocalization across GWAS traits while assessing the causality and directionality of genetic associations. Methods We applied colocalization between T2D and 20 related metabolic traits, across 243 loci, to obtain inferences of shared casual variants. Network-based unsupervised hierarchical clustering was performed on variant-trait associations. Partitioned polygenic risk scores (PRSs) were generated for each cluster using T2D summary statistics and validated in 21,742 individuals with T2D from 3 cohorts. Inferences of directionality and causality were obtained by applying Mendelian randomization Steiger’s Z-test and further validated in a pediatric cohort without diabetes (aged 9–12 years old, n = 3866). Results We identified 146 T2D loci that colocalized with at least one metabolic trait locus. T2D variants within these loci were grouped into 5 clusters. The clusters corresponded to the following pathways: obesity, lipodystrophic insulin resistance, liver and lipid metabolism, hepatic glucose metabolism, and beta-cell dysfunction. We observed heterogeneity in associations between PRSs and metabolic measures across clusters. For instance, the lipodystrophic insulin resistance (Beta − 0.08 SD, 95% CI [− 0.10–0.07], p = 6.50 × 10−32) and beta-cell dysfunction (Beta − 0.10 SD, 95% CI [− 0.12, − 0.08], p = 1.46 × 10−47) PRSs were associated to lower BMI. Mendelian randomization Steiger analysis indicated that increased T2D risk in these pathways was causally associated to lower BMI. However, the obesity PRS was conversely associated with increased BMI (Beta 0.08 SD, 95% CI 0.06–0.10, p = 8.0 × 10−33). Analyses within a pediatric cohort supported this finding. Additionally, the lipodystrophic insulin resistance PRS was associated with a higher odds of chronic kidney disease (OR 1.29, 95% CI 1.02–1.62, p = 0.03). Conclusions We successfully partitioned T2D genetic variants into phenotypic pathways using a colocalization first approach. Partitioned PRSs were associated to unique metabolic and clinical outcomes indicating successful partitioning of disease heterogeneity. Our work expands on previous approaches by providing stronger inferences of shared causal variants, causality, and directionality of GWAS variant-trait associations.

Abstract Background Research into Artificial Placenta and Artificial Womb (APAW) technology for extremely premature infants (born < 28 weeks of gestation) is currently being conducted in animal studies and shows promising results. Because of the unprecedented nature of a potential treatment and the high-risk and low incidence of occurrence, translation to the human condition is a complex task. Consequently, the obstetric procedure, the act of transferring the infant from the pregnant woman to the APAW system, has not yet been established for human patients. The use of simulation-based user-centered development allows for a safe environment in which protocols and devices can be conceptualized and tested. Our aim is to use participatory design principles in a simulation context, to gain and integrate the user perspectives in the early design phase of a protocol for this novel procedure. Methods Simulation protocols and prototypes were developed using an iterative participatory design approach; usability testing, including general and task-specific feedback, was obtained from participants with clinical expertise from a range of disciplines. The procedure made use of fetal and maternal manikins and included animations and protocol task cards. Results Physical simulation with the active participation of clinicians led to the diffusion of tacit knowledge and an iteratively formed shared understanding of the requirements and values that needed to be implemented in the procedure. At each sequel, participant input was translated into simulation protocols and design adjustments. Conclusion This work demonstrates that simulation-based participatory design can aid in shaping the future of clinical procedure and product development and rehearsing future implementation with healthcare professionals.