Strain Patterns With Ultrasound for Assessment of Abdominal Aortic Aneurysm Vessel Wall Biomechanics.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are an important cause of death. Small AAAs are surveyed with ultrasound (US) until a defined diameter threshold, often triggering a computer tomography scan and surgical repair. Nevertheless, 5%-10% of AAA ruptures are below threshold, and some large AAAs never rupture. AAA wall biomechanics may reveal vessel wall degradation with potential for patient-centred risk assessment. This clinical study investigated AAA vessel wall biomechanics and deformation patterns, including reproducibility. METHODS: In 50 patients with AAA, 183 video clips were recorded by two sonographers. Prototype software extracted AAA vessel wall principal strain characteristics and patterns. Functional principal component analysis (FPCA) derived strain pattern statistics. RESULTS: Strain patterns demonstrated reduced AAA wall strains close to the spine. The strain pattern "topography" (i.e., curve phases or "peaks" and "valleys") had a 3.9 times lower variance than simple numeric assessment of strain amplitudes, which allowed for clustering in two groups with FPCA. A high mean reproducibility of these clusters of 87.6% was found. Median pulse pressure-normalised mean principal strain (PPPS) was 0.038%/mm Hg (interquartile range: 0.029-0.051%/mm Hg) with no correlation to AAA size (Spearman's ρ = 0.02, false discovery rate-p = 0.15). Inter-operator reproducibility of PPPS was poor (limits of agreement: ±0.031%/mm Hg). DISCUSSION: Strain patterns challenge previous numeric stiffness measures based on anterior-posterior-diameter and are reproducible for clustering. This study's PPPS aligned with prior findings, although clinical reproducibility was poor. In contrast, US-based strain patterns hold promising potential to enhance AAA risk assessment beyond traditional diameter-based metrics.

No shortening of the patellar tendon during two-stage total knee arthroplasty revision using articulating spacers.

BACKGROUND: Surgical techniques in two-stage revision total knee arthroplasty (rTKA) include the use of articulating spacers and static spacers. Shortening of the patellar tendon could be a reason for inferior functional outcomes in two-stage septic rTKA . The aim of this study was to determine if articulating spacers also have negative effects on the extensor mechanism in rTKA. METHODS: This retrospective study includes 65 consecutive patients (23 women, 42 men, age 71.3 ± 1.2; range, 51.2-88.6 years) undergoing septic two-stage rTKA using an articulating spacer between 2014 and 2021 in a single orthopedic center. For all patients, calibrated true lateral radiographs before total knee arthroplasty (TKA) explantation (T0), directly after TKA explantation (T1), shortly before TKA reimplantation (T2) and 6-8 days after TKA reimplantation (T3) were used to calculate the modified Insall Salvati ratio (mISR). RESULTS: Overall, the mISR decreased significantly immediately after explantation (T0 vs. T1, p = 0.002) from 1.43 ± 0.03 to 1.36 ± 0.03 and remained stable until T2 (1.37 ± 0.02, p = 0.74). Following TKA reimplantation, the mISR increased again to 1.43 ± 0.03 (T3). There were no significant differences between T0 and T3 (p = 0.88). Six out of 65 patients (9%) experienced patellar tendon shortening > 10% at T3. CONCLUSIONS: Septic two-stage revision TKA using an articulating spacer does not lead to patellar tendon shortening in the majority of cases. This study suggests that one reason for the improved range of motion after reimplantation may be the use of articulating spacers compared to static spacers.

Relationship Between Intraluminal Thrombus Volume and Circulating ADAMTS-13 Activity in Abdominal Aortic Aneurysms.

Introduction: Abdominal aortic aneurysms (AAAs) with intraluminal thrombus (ILT) are suggested to be more prone to rupture than AAAs without. Prior studies indicate that the von Willebrand factor (vWf) plays a role in the formation of ILT since a positive correlation between ILT volume and vWf has been shown. vWf mediates the tethering of platelets at sites of endothelial injury, and the protease ADAMTS-13 cleaves larger forms of vWf, thus counteracting the thrombosis cascade and maintaining haemostatic balance. When investigating the largest quantifiable thrombus in the human body, it was hypothesised that circulating ADAMTS-13 activity may be associated with ILT size in patients with AAA and the aim was to explore this potential relationship using 3D contrast enhanced ultrasound (3D-CEUS) for ILT volume determination. Report: In this retrospective, exploratory study, 60 patients with AAA were evaluated, and the association between ILT volume and thickness and ADAMTS-13 was estimated using 3D-CEUS. ADAMTS-13 activity was measured in plasma samples obtained the same day. No association between ILT volume (r = -0.03, p = 0.84) or ILT thickness (r = 0.02, p = 0.87) and ADAMTS-13 activity was found. Likewise, when subdividing the group into lowest and highest 50% of ADAMTS-13 activity, the half with the lowest ADAMTS-13 activity (mean ILT volume ±standard deviation [SD]: 32 ± 34 mL) did not differ from the half with the highest ADAMTS-13 activity (43 ± 24 mL) when comparing ILT volume (p = 0.172, F = 2.95) and thickness (p = 0.070). Discussion: After evaluating the largest quantifiable intraluminal thrombus in the vasculature, it was concluded that, surprisingly, circulating ADAMTS-13 activity seems unrelated to ILT formation in AAA.

Automated 3D ultrasound bridges the gap between novices and experts in diameter assessment of abdominal aortic aneurysms.

BACKGROUND: The current management of abdominal aortic aneurysm (AAA) hinges upon assessing diameter using ultrasound (US). Diameter reproducibility with conventional two-dimensional ultrasound (2D-US) is challenging and requires experienced operators. A novel automatic three-dimensional ultrasound (3D-US) system enables on-cart software-assisted diameter estimation (3D-SAUS), potentially facilitating more precise diameter measurements than 2D-US. This study aimed to assess the variance of AAA diameter measurements among US novices and experts by comparing 2D-US with 3D-SAUS in a clinical setting. METHODS: A total of 580 US scans were scheduled by 29 US operators (13 experts and 16 novices) on 10 patients with AAAs. Experts and novices measured all patients' AAA anterior-posterior (AP) diameters with 2D-US and 3D-SAUS. Outcomes were limits of agreement (LoA) using a mixed-effects model. RESULTS: In total, 564 of 580 planned US scans were performed. 500 US scans were automatically analyzed by the software and included. When using 3D-SAUS instead of 2D-US, novices reduced their LoA from ±16.5% to ±10.2% (P<0.001), reaching the experts' LoA of ±10.5% (P=0.782 for difference). The experts' LoA was ±10.5% for 2D-US and ±9.7% for 3D-SAUS, with no statistically significant difference between the two modalities (P=0.423). CONCLUSIONS: Clinical implementation of the 3D-SAUS demonstrates a substantial reduction in variance in AAA diameter measurements among novice sonographers, surpassing the performance of conventional 2D-US techniques. Additionally, using the 3D-SAUS tool enables novice sonographers to achieve proficiency levels comparable to those of experts employing conventional 2D-US.

optiPRM: A Targeted Immunopeptidomics LC-MS Workflow With Ultra-High Sensitivity for the Detection of Mutation-Derived Tumor Neoepitopes From Limited Input Material.

Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for the improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft from as little as 2.5 × 106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.

Social sharing of emotion during the collective crisis of COVID-19.

We collected data from two sources - social media and online questionnaires - to investigate the emotional consequences of social sharing during the COVID-19 pandemic. Study 1 tracked and analysed sentiment of tweets posted over the course of a month in the crisis period and found that users who tweeted more frequently about COVID-19 expressed decreasing negative sentiment and increasing positive sentiment over time. Granger causality tests confirmed that this association was better interpreted in the forward direction (sharing levels predicting sentiment) than in the reverse direction (sentiment predicting sharing levels). Study 2 focused on immediate emotional consequences of sharing COVID-19-related events and found that participants reported improved overall affect about an event after sharing it, especially when that event was a personal experience rather than a news story. Reported positive feelings about both kinds of events were also significantly higher after sharing. Taken together, both studies suggested that social sharing is linked with emotional relief and may therefore help people to deal with their negative experiences during a persistent collective crisis.

E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network.

Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with the formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acid, and lipid metabolism. 5'-Phosphoribosyl-N-formylglycinamide, a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase, which catalyzes 5'-phosphoribosyl-N-formylglycinamide synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTP depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTP reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis. SIGNIFICANCE: Maintenance of genome stability prevents disease and affiliates with growth factor receptor tyrosine kinases. We identified de novo purine synthesis as a pathway in which key enzymatic players are regulated through MET receptor and whose depletion via MET targeting explains MET inhibition-associated formation of DNA double-strand breaks. The mechanistic importance of MET inhibition-dependent E2F1 downregulation for interference with DNA integrity has translational implications for MET-targeting-based treatment of malignancies.

No effects of acute stress on monetary delay discounting: A systematic literature review and meta-analysis.

Many everyday decisions, including those concerning our health, finances and the environment, involve choosing between a smaller but imminent reward (e.g., €20 now) and a later but larger reward (e.g., €40 in a month). The extent to which an individual prefers smaller imminent rewards over larger delayed rewards can be measured using delay discounting tasks. Acute stress induces a cascade of biological and psychological responses with potential consequences for how individuals think about the future, process rewards, and make decisions, all of which can impact delay discounting. Several studies have shown that individuals focus more on imminent rewards under stress. These findings have been used to explain why individuals make detrimental choices under acute stress. Yet, the evidence linking acute stress to delay discounting is equivocal. To address this uncertainty, we conducted a meta-analysis of 11 studies (14 effects) to systematically quantify the effects of acute stress on monetary delay discounting. Overall, we find no effect of acute stress on delay discounting, compared to control conditions (SMD = -0.18, 95% CI [-0.57, 0.20], p = 0.32). We also find that neither the gender/sex of the participants, the type of stressor (e.g., physical vs. psychosocial) nor whether monetary decisions were hypothetical or incentivized (i.e. monetary decisions were actually paid out) moderated the impact of acute stress on monetary delay discounting. We argue that establishing the effects of acute stress on the separate processes involved in delay discounting, such as reward valuation and prospection, will help to resolve the inconsistencies in the field.

Copenhagen Mesenteric stent study (COMESS)-a randomized trial of stent versus covered stent treatment for chronic mesenteric ischemia.

BACKGROUND: Current management of mesenteric ischemia is primarily endovascular stent treatment. Typical CMI symptoms are postprandial abdominal pain, food fear, weight loss, and diarrhea. Revascularization is often necessary, as mesenteric ischemia may progress to bowel necrosis and death if left untreated. This study aims to compare the outcome using bare metal stent (BMS) or covered stent (CS) in the endovascular treatment of chronic and acute on chronic mesenteric ischemia. METHODS: This is an investigator-driven, prospective, randomized, single-blinded, and single-center, national cohort study at the Copenhagen University Hospital, Denmark. A total of 98 patients with chronic mesenteric ischemia (CMI) and acute-on-chronic mesenteric ischemia (AoCMI) will be randomized to treatment with either BeSmooth BMS (Bentley Innomed GmbH) or BeGraft CS (Bentley Innomed GmbH). Randomization occurs intraoperatively after lesion crossing. DISCUSSION: There is currently no published data from prospective controlled trials regarding the preferred type of stent used for the treatment of chronic and acute-on-chronic mesenteric ischemia. This trial will evaluate the short- and long-term outcome of BMS versus CS when treating CMI and AoCMI, as well as the benefit of a more intense postoperative surveillance program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05244629. Registered on February 8, 2022.

Removal of a large symptomatic retrocardiac mediastinal lipoma.

Large mediastinal lipomas are rare. Complete surgical resection can be difficult due to the intricate anatomy in the mediastinum. We report the case of a 75-year-old man with worsened retrosternal pressure, decline in performance and syncope episodes. Computed tomography revealed a large retrocardiac low-attenuated mediastinal lesion measuring 10 × 8 cm, compressing the left atrium and pulmonary veins bilaterally. Surgical exploration was achieved through a right anterolateral thoracotomy with a successful en bloc resection without any intraoperative complications. The total operation time was 185 min with a total blood loss of <250 ml. Stand-by extracorporeal life support was present throughout the procedure, but its use was not required. The postoperative course was uneventful. The pathological examination revealed a mature mediastinal lipoma without any evidence of malignancy. In the 12-month control the patient was completely free of symptoms and in a good general condition.

HIV viral suppression and risk of viral rebound in patients on antiretroviral therapy: a two- year retrospective cohort study in Northern Tanzania.

BACKGROUND: The world is moving towards the third target of the Joint United Nations Programme on HIV/AIDS to ensure most people receiving antiretroviral therapy (ART) are virologically suppressed. Little is known about viral suppression at an undetectable level and the risk of viral rebound phenomenon in sub-Saharan Africa which covers 67% of the global HIV burden.This study aimed to investigate the proportion of viral suppression at an undetectable level and the risk of viral rebound among people living with HIV receiving ART in northern Tanzania. METHODOLOGY: A hospital based-retrospective study recruited people living with HIV who were on ART for at least two years at Kibong'oto Infectious Disease Hospital and Mawenzi Regional Referral Hospital in Kilimanjaro Region, Tanzania. Participants' two-year plasma HIV were captured at months 6, 12, and 24 of ART. Undetectable viral load was defined by plasma HIV of viral load (VL) less than 20copies/ml and viral rebound (VR) was considered to anyone having VL of more than 50 copies/ml after having history of undetectable level of the VL less than 20copies/ml. A multivariable log-binomial generalized linear model was used to determine factors for undetectable VL and viral VR. RESULTS: Among 416 PLHIV recruited, 226 (54.3%) were female. The mean (standard deviation) age was 43.7 (13.3) years. The overall proportion of undetectable VL was 68% (95% CI: 63.3-72.3) and 40.0% had viral rebound (95% CI: 34.7-45.6). Participants who had at least 3 clinic visits were 1.3 times more likely to have undetectable VL compared to those who had 1 to 2 clinic visits in a year (p = 0.029). Similarly, participants with many clinical visits ( > = 3 visits) per year were less likely to have VR compared to those with fewer visits ( = 2 visits) [adjusted relative risk (aRR) = 0.64; 95% CI: 0.44-0.93]. CONCLUSION: Participants who had fewer clinic visits per year(ART refills) were less likely to achieve viral suppression and more likely to experience viral rebound. Enhanced health education and close follow-up of PLHIV on antiretroviral therapy are crucial to reinforce adherence and maintain an undetectable viral load.

Binary Coalescences as Sources of Ultrahigh-Energy Cosmic Rays.

Binary coalescences are known sources of gravitational waves (GWs) and they encompass combinations of black holes (BHs) and neutron stars (NSs). Here we show that when BHs are embedded in magnetic fields (B's) larger than approximately 10^{10} G, charged particles colliding around their event horizons can easily have center-of-mass energies in the range of ultrahigh energies (≳10^{18} eV) and become more likely to escape. Such B-embedding and high-energy particles can take place in BH-NS binaries, or even in BH-BH binaries with one of the BHs being charged (with charge-to-mass ratios as small as 10^{-5}, which do not change GW waveforms) and having a residual accretion disk. Ultrahigh center-of-mass energies for particle collisions arise for basically any rotation parameter of the BH when B≳10^{10} G, meaning that it should be a common aspect in binaries, especially in BH-NS ones given the natural presence of a B onto the BH and charged particles due to the magnetosphere of the NS. We estimate that the number of ultrahigh center-of-mass collisions ranges from a few up to millions before the merger of binary compact systems. Thus, binary coalescences may also be efficient sources of ultrahigh energy cosmic rays (UHECRs) and constraints to NS/BH parameters would be possible if UHECRs are detected along with GWs.

Foreign Glass Bodies in Pleura and Pancreas: Systematic Review for Entry Hypotheses and Treatment Options in an Unresolved Case.

BACKGROUND: Foreign bodies within the pleura and pancreas are infrequent, and the approaches to their treatment still a subject of debate. There is limited knowledge particularly regarding glass foreign bodies. METHODS: We present a case involving large glass splinters in the pleura and pancreas, with an unknown entry point. In addition, a systematic review was conducted to explore entry hypotheses and management options. RESULTS: In addition to our case, our review uncovered eight incidents of intrapleural glass, and another eight cases of glass in other intrathoracic areas. The fragments entered the body through impalement (81%), migrated through the diaphragm after impalement (6%), or caused transesophageal perforation (19%) following ingestion. Eight instances of glass inside the abdominal cavity were documented, with seven resulting from impalement injuries and one from transintestinal migration. There were no recorded instances of glass being discovered within the pancreas. Among the 41 nonglass intrapancreatic foreign bodies found, sewing needles (34%) and fish bones (46%) were the most common; following ingestion, they had migrated through either a transgastric or transduodenal perforation. In all these cases, how the foreign bodies were introduced was often poorly recalled by the patient. Many nonglass foreign bodies tend to become encapsulated by fibrous tissue, rendering them inert, though this is less common with glass. Glass has been reported to migrate through various tissues and cavities, sometimes with a significant delay spanning even decades. There are cases of intrapleural migration of glass causing hemothorax, pneumothorax, and heart and major blood vessels injury. For intrapleural glass fragment management, thoracoscopy proved to be effective in 5 reported cases, in addition to our patient. Most intrapancreatic nonglass foreign bodies tend to trigger pancreatitis and abscess formation, necessitating management ranging from laparoscopic procedures to subtotal pancreatectomy. There have been only four documented cases of intrapancreatic needles that remained asymptomatic with conservative management. There is no direct guidance from the existing literature regarding management of intrapancreatic glass foreign bodies. Consequently, our patient is under observation with regular follow-ups and has remained asymptomatic for the past 2 years. CONCLUSIONS: Glass foreign bodies in the pleura are rare, and our report of an intrapancreatic glass fragment is the first of its kind. Impalement is the most likely method of introduction. As glass has significant migration and an ensuing complication potential, preventive removal of intrapleural loose glass should be considered. However, intrapancreatic glass fragment management remains uncertain.

Standard precautions compliance and its associated factors among nurses in Kazakhstan: A cross-sectional study.

BACKGROUND: During the COVID-19 pandemic, with many nurses being infected, understanding compliance with standard precautions (SP) among nurses in Kazakhstan is crucial for improving infection prevention and control and preparedness for future emergencies. The study aimed to assess Kazakh nurses' SP compliance amid the COVID-19 pandemic and examine the factors associated with their compliance. METHODS: Quantitative, cross-sectional design. This research surveyed 241 clinical nurses in Astana, Kazakhstan using a standardized tool from December 2021 to April 2022. RESULTS: This study found 76.0% SP compliance among the nurses. The highest compliance was observed in the dimension "Decontamination of spills and used articles" (86.0% compliance rate), followed by "Use of protective devices" (83.5% compliance rate), "Prevention of cross-infection from person to person" (72.7% compliance rate), "Disposal of sharps" (65.4% compliance rate), and "Disposal of waste" (56.0% compliance rate). Nurses' age and educational qualification influences the nurses' SP compliance. DISCUSSION: While the nurses' compliance rate in this study was moderate, specific areas warrant more attention, such as their compliance with proper waste and sharps disposal. CONCLUSIONS: This study highlighted the experiences of nurses in Kazakhstan on their compliance with SP during the pandemic.

Impact of intra- and extramedullary alignment on blood loss in total knee arthroplasty: a retrospective study.

BACKGROUND: There is a scarcity of scientific data regarding the correlation between alignment techniques during total knee arthroplasty (TKA) and blood loss as well as transfusion rates. This study's hypothesis posited that intramedullary-aligned (IM) TKA exhibits higher blood loss and transfusion rates when contrasted with extramedullary-aligned (EM) TKA. METHODS: We conducted a retrospective examination of 883 patients who underwent total knee arthroplasty (TKA) in 2021 at a solitary orthopedic center in Germany. These patients were divided into two groups based on their tibial alignment technique: extramedullary alignment and intramedullary tibial alignment. RESULTS: In the intramedullary tibial alignment (IM) group, we observed a blood loss of 0.91 L, while in the extramedullary tibial alignment (EM) group, the blood loss was 0.89 L. These values did not demonstrate a significant difference (p = 0.69). Transfusion rates were 0.99% in the IM group and 0.21% in the EM group, and there was no significant distinction between them (Chi-squared test: p > 0.05). CONCLUSION: We observed no statistically significant variance in blood loss between the IM and EM groups. Likewise, there was no substantial disparity in transfusion rates between these groups. It can be concluded that the selection of a knee arthroplasty system incorporating either intramedullary tibial alignment or extramedullary alignment does not significantly impact blood loss.

Proteomic analysis of the extracellular matrix of human atherosclerotic plaques shows marked changes between plaque types.

Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.

Certification of Basic Skills in Endovascular Aortic Repair Through a Modular Simulation Course With Real Time Performance Assessment.

OBJECTIVE: Endovascular aortic repair (EVAR) is being used increasingly for the treatment of infrarenal abdominal aortic aneurysms. Improvement in educational strategies is required to teach future vascular surgeons EVAR skills, but a comprehensive, pre-defined e-learning and simulation curriculum remains to be developed and tested. EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE), an assessment tool for simulation based education (SBE) in EVAR, has previously been designed to assess EVAR skills, and a pass limit defining mastery level has been set. However, EVARATE was developed for anonymous video ratings in a research setting, and its feasibility for real time ratings in a standardised SBE programme in EVAR is unproven. This study aimed to test the effect of a newly developed simulation based modular course in EVAR. In addition, the applicability of EVARATE for real time performance assessments was investigated. METHODS: The European Society of Vascular Surgery (ESVS) and Copenhagen Certification Programme in EVAR (ENHANCE-EVAR) was tested in a prospective cohort study. ENHANCE-EVAR is a modular SBE programme in EVAR consisting of e-learning and hands-on SBE. Participants were rated with the EVARATE tool by experienced EVAR surgeons. RESULTS: Twenty-four physicians completed the study. The mean improvement in EVARATE score during the course was +11.8 (95% confidence interval 9.8 - 13.7) points (p < .001). Twenty-two participants (92%) passed with a mean number of 2.8 ± 0.7 test attempts to reach the pass limit. Cronbach's alpha coefficient was 0.91, corresponding to excellent reliability of the EVARATE scale. Differences between instructors' EVARATE ratings were insignificant (p = .16), with a maximum variation between instructors of ± 1.3 points. CONCLUSION: ENHANCE-EVAR, a comprehensive certifying EVAR course, was proven to be effective. EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE) is a trustworthy tool for assessing performance within an authentic educational setting, enabling real time feedback.

Genetic diversity and divergence among native and translocated populations of the golden flathead goby Glossogobius aureus (Gobiiformes: Gobiidae) in Philippine lakes.

The golden flathead goby Glossogobius aureus is a native species in the Philippines, Australia, Japan, Taiwan, and many other countries in Asia. In the Philippines, it is an important food fish as it is commonly caught in major lakes. In this study, a total of 307 specimens morphologically identified as G. aureus were sampled from nine major lakes in the Philippines and were sequenced for their mitochondrial cytochrome b (cyt b) gene. Two hundred sixty of the 307 cyt b sequences had sequence similarities of ≥ 99% with G. aureus reference sequence in GenBank, while the remaining 47 (all from Lake Lanao) had sequence similarities of only 95% and were thus designated as Glossogobius cf. aureus and treated as a separate population. The sequences were then analyzed to examine the pattern of genetic diversity, relatedness, divergence, and demographic history among native and translocated populations of the species. Twenty-nine haplotypes were recovered, of which four haplotypes were shared among three to seven populations. Only one haplotype each was found in the native population in Lake Buhi and translocated population in Lake Paoay. Low haplotype and low nucleotide diversities were found for the populations in Laguna de Bay, Lanao, Bato, Buhi, Paoay, and Sebu lakes, which indicate founder event for the introduced populations in Lanao, Paoay, and Sebu lakes and recent genetic bottleneck for the native populations in Laguna de Bay, Bato, and Buhi. In contrast, high haplotype but low nucleotide diversities were found for the native populations of Taal, Naujan, and Buluan lakes, signifying a recent bottleneck followed by population expansion. Pairwise FST values showed generally large (FST = 0.168-0.249) to very large (FST = 0.302-1.000) genetic divergence between populations except between Laguna de Bay and Lake Bato, Laguna de Bay and Lake Buhi, and Lake Bato and Lake Buhi populations, which showed nonsignificant genetic differentiation. Lake Buluan and Lake Sebu populations showed moderate genetic differentiation (FST = 0.098). Neutrality tests showed significant negative Tajima's D and Fu's FS values only for the population from Laguna de Bay, which suggests that the population is undergoing expansion. These results are important for establishing scientifically sound strategies for effective conservation and sustainable exploitation of G. aureus in the Philippines.