Protein analysis by desorption electrospray ionization mass spectrometry.

This review presents progress made in the ambient analysis of proteins, in particular by desorption electrospray ionization-mass spectrometry (DESI-MS). Related ambient ionization techniques are discussed in comparison to DESI-MS only to illustrate the larger context of protein analysis by ambient ionization mass spectrometry. The review describes early and current approaches for the analysis of undigested proteins, native proteins, tryptic digests, and indirect protein determination through reporter molecules. Applications to mass spectrometry imaging for protein spatial distributions, the identification of posttranslational modifications, determination of binding stoichiometries, and enzymatic transformations are discussed. The analytical capabilities of other ambient ionization techniques such as LESA and nano-DESI currently exceed those of DESI-MS for in situ surface sampling of intact proteins from tissues. This review shows, however, that despite its many limitations, DESI-MS is making valuable contributions to protein analysis. The challenges in sensitivity, spatial resolution, and mass range are surmountable obstacles and further development and improvements to DESI-MS is justified.

Comparison of scoring systems for predicting clinical outcomes of acute lower gastrointestinal bleeding: A prospective cohort study.

BACKGROUND: This study aimed to determine the performance of the Oakland, Glasgow-Blatchford, and AIMS65 scores in predicting the clinical outcomes of acute lower gastrointestinal bleeding (LGIB). METHODS: This prospective cohort study was conducted from July 2020 to July 2021. Patients admitted with acute lower gastrointestinal bleeding were enrolled. The Oakland, Glasgow-Blatchford, and AIMS65 scores were calculated. The primary outcome was validating the performance of the scores in predicting severe LGIB; secondary outcomes were comparing the performance of the scores in predicting the need for blood transfusion, hemostatic interventions, in-hospital rebleeding, and mortality. Receiver operating characteristic curves were calculated for all outcomes. The associations between all three scores and the primary outcomes were calculated using multivariate logistic regression analysis. RESULTS: Patients with acute LGIB (n = 150) were enrolled (88 [58.7%] men and mean age: 63.6 ± 17.3 years). The rates of severe LGIB, need for blood transfusion, hemostatic intervention, in-hospital rebleeding, and in-hospital mortality were 54.7%, 79.3%, 10.7%, and 3.3%, respectively. The Oakland and Glasgow-Blatchford scores had comparable performance in predicting severe LGIB, need for blood transfusion, and mortality, outperforming the AIMS65 score. All scores were suboptimal for predicting hemostatic interventions and rebleeding. CONCLUSIONS: Our results demonstrate the predictive performances of the Oakland score and the GBS are excellent and comparable for severe LGIB, the need for blood transfusion, and in-hospital mortality in patients with acute LGIB. Thus, GBS could be considered as an alternative predictive score for stratification of the patients with acute LGIB.

Global and Local Ancestry and its Importance: A Review.

The fastest way to significantly change the composition of a population is through admixture, an evolutionary mechanism. In animal breeding history, genetic admixture has provided both short-term and long-term advantages by utilizing the phenomenon of complementarity and heterosis in several traits and genetic diversity, respectively. The traditional method of admixture analysis by pedigree records has now been replaced greatly by genome-wide marker data that enables more precise estimations. Among these markers, SNPs have been the popular choice since they are cost-effective, not so laborious, and automation of genotyping is easy. Certain markers can suggest the possibility of a population's origin from a sample of DNA where the source individual is unknown or unwilling to disclose their lineage, which are called Ancestry-Informative Markers (AIMs). Revealing admixture level at the locus-specific level is termed as local ancestry and can be exploited to identify signs of recent selective response and can account for genetic drift. Considering the importance of genetic admixture and local ancestry, in this mini-review, both concepts are illustrated, encompassing basics, their estimation/identification methods, tools/software used and their applications.

Prediction of 30-day in-hospital mortality in older UGIB patients using a simplified risk score and comparison with AIMS65 score.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) in older patients is associated with substantial in-hospital morbidity and mortality. This study aimed to develop and validate a simplified risk score for predicting 30-day in-hospital mortality in this population. METHODS: A retrospective analysis was conducted on data from 1899 UGIB patients aged ≥ 65 years admitted to a single medical center between January 2010 and December 2019. An additional cohort of 330 patients admitted from January 2020 to October 2021 was used for external validation. Variable selection was performed using five distinct methods, and models were generated using generalized linear models, random forest, support vector machine, and k-nearest neighbors approaches. The developed score, "ABCAP," incorporated Albumin < 30 g/L, Blood Urea Nitrogen (BUN) > 7.5 mmol/L, Cancer presence, Altered mental status, and Pulse rate > 100/min, each assigned a score of 1. Internal and external validation procedures compared the ABCAP score with the AIMS65 score. RESULTS: In internal validation, the ABCAP score demonstrated robust predictive capability with an area under the curve (AUC) of 0.878 (95% CI: 0.824-0.932), which was significantly better than the AIMS65 score (AUC: 0.827, 95% CI: 0.751-0.904), as revealed by the DeLong test (p = 0.048). External validation of the ABCAP score resulted in an AUC of 0.799 (95% CI: 0.709-0.889), while the AIMS65 score yielded an AUC of 0.743 (95% CI: 0.647-0.838), with no significant difference between the two scores based on the DeLong test (p = 0.16). However, the ABCAP score at the 3-5 score level demonstrated superior performance in identifying high-risk patients compared to the AIMS65 score. This score exhibited consistent predictive accuracy across variceal and non-variceal UGIB subgroups. CONCLUSIONS: The ABCAP score incorporates easily obtained clinical variables and demonstrates promising predictive ability for 30-day in-hospital mortality in older UGIB patients. It allows effective mortality risk stratification and showed slightly better performance than the AIMS65 score. Further cohort validation is required to confirm generalizability.

A pragmatic methodology to extract anesthetic and physiological data from the electronic health record.

BACKGROUND/AIMS: Traditional manual methods of extracting anesthetic and physiological data from the electronic health record rely upon visual transcription by a human analyst that can be labor-intensive and prone to error. Technical complexity, relative inexperience in computer coding, and decreased access to data warehouses can deter investigators from obtaining valuable electronic health record data for research studies, especially in under-resourced settings. We therefore aimed to develop, pilot, and demonstrate the effectiveness and utility of a pragmatic data extraction methodology. METHODS: Expired sevoflurane concentration data from the electronic health record transcribed by eye was compared to an intermediate preprocessing method in which the entire anesthetic flowsheet narrative report was selected, copy-pasted, and processed using only Microsoft Word and Excel software to generate a comma-delimited (.csv) file. A step-by-step presentation of this method is presented. Concordance rates, Pearson correlation coefficients, and scatterplots with lines of best fit were used to compare the two methods of data extraction. RESULTS: A total of 1132 datapoints across eight subjects were analyzed, accounting for 18.9 h of anesthesia time. There was a high concordance rate of data extracted using the two methods (median concordance rate 100% range [96%, 100%]). The median time required to complete manual data extraction was significantly longer compared to the time required using the intermediate method (240 IQR [199, 482.5] seconds vs 92.5 IQR [69, 99] seconds, p = .01) and was linearly associated with the number of datapoints (rmanual = .97, p < .0001), whereas time required to complete data extraction using the intermediate approach was independent of the number of datapoints (rintermediate = -.02, p = .99). CONCLUSIONS: We describe a pragmatic data extraction methodology that does not require additional software or coding skills intended to enhance the ease, speed, and accuracy of data collection that could assist in clinician investigator-initiated research and quality/process improvement projects.

The role of medical schools in UK students' career intentions: findings from the AIMS study.

OBJECTIVES: To investigate differences in students' career intentions between UK medical schools. DESIGN: Cross-sectional, mixed-methods online survey. SETTING: The primary study included all 44 UK medical schools, with this analysis comprising 42 medical schools. PARTICIPANTS: Ten thousand four hundred eighty-six UK medical students. MAIN OUTCOME MEASURES: Career intentions of medical students, focusing on differences between medical schools. Secondary outcomes included variation in medical students' satisfaction with a prospective career in the NHS, by medical school. RESULTS: 2.89% of students intended to leave medicine altogether, with Cambridge Medical School having the highest proportion of such respondents. 32.35% of respondents planned to emigrate for practice, with Ulster medical students being the most likely. Of those intending to emigrate, the University of Central Lancashire saw the highest proportion stating no intentions to return. Cardiff Medical School had the greatest percentage of students intending to assume non-training clinical posts after completing FY2. 35.23% of participating medical students intended to leave the NHS within 2 years of graduating, with Brighton and Sussex holding the highest proportion of these respondents. Only 17.26% were satisfied with the prospect of working in the NHS, with considerable variation nationally; Barts and the London medical students had the highest rates of dissatisfaction. CONCLUSIONS: This study reveals variability in students' career sentiment across UK medical schools, emphasising the need for attention to factors influencing these trends. A concerning proportion of students intend to exit the NHS within 2 years of graduating, with substantial variation between institutions. Students' intentions may be shaped by various factors, including curriculum focus and recruitment practices. It is imperative to re-evaluate these aspects within medical schools, whilst considering the wider national context, to improve student perceptions towards an NHS career. Future research should target underlying causes for these disparities to facilitate improvements to career satisfaction and retention.

Generating real-world evidence in Alzheimer's disease: Considerations for establishing a core dataset.

Ongoing assessment of patients with Alzheimer's disease (AD) in postapproval studies is important for mapping disease progression and evaluating real-world treatment effectiveness and safety. However, interpreting outcomes in the real world is challenging owing to variation in data collected across centers and specialties and greater heterogeneity of patients compared with trial participants. Here, we share considerations for observational postapproval studies designed to collect harmonized longitudinal data from individuals with mild cognitive impairment or mild dementia stage of disease who receive therapies targeting the underlying pathological processes of AD in routine practice. This paper considers key study design parameters, including proposed aims and objectives, study populations, approaches to data collection, and measures of cognition, functional abilities, neuropsychiatric status, quality of life, health economics, safety, and drug utilization. Postapproval studies that capture these considerations will be important to provide standardized data on AD treatment effectiveness and safety in real-world settings.

Metformin-'BRAINS & AIMS' pharmacological/prescribing principles of commonly prescribed (Top 100) drugs: Education and discussion.

We review pharmacological/prescribing principles relating to metformin according to our mnemonic framework: 'BRAINS & AIMS' (Benefits, Risks, Adverse Effects, Interactions, Necessary prophylaxis, Susceptibilities, Administering, Informing, Monitoring and Stopping): Benefits: Metformin's licensed uses: Type 2 diabetes mellitus (T2DM) treatment, reduction in risk or delay of onset. No clear evidence metformin influences patient-important outcomes [Cochrane Review (2020) of 18 RCTs (n = 10 680)]. Risks: Inexpensive, essential WHO list drug; use contraindicated/not tolerated in 15%: for example, contraindication: lactic acidosis in renal impairment (eGFR <30 mL/min/1.73 m2 ). Adverse effects: Common gastrointestinal (GI) side effects are dose-related and include abdominal pain, decreased appetite, diarrhoea (usually transient), nausea and vomiting, altered taste; vitamin B12 deficiency. Rare: acute metabolic acidosis (lactic acidosis/diabetic ketoacidosis). Interactions (pharmacokinetic) occur with drugs impairing renal function and hence metformin excretion, and drugs inhibiting organic cation transporter 1 or 2 (OCT1, OCT2), and/or multidrug and toxin extrusion protein 1 (MATE1/2-K), such as cimetidine, ranolazine, trimethoprim and verapamil, and inducers such as rifampicin. The risk of hypoglycaemia may increase when metformin is used in combination with other medications for diabetes (pharmacodynamic interaction). Necessary prophylaxis: Detect/treat vitamin B12 deficiency. Susceptible groups: Elderly/renal/liver impairment (lactic acidosis); safe in pregnancy/breastfeeding. Administering: Initially 500 mg once daily (morning) with breakfast; titrate only after 1 week. Informing (relevant BRAINS & A(I)MS principles). Monitoring: Renal function beforehand, and 6-12 monthly, HbA1c 3-6 monthly until controlled. Serum vitamin B12 levels if deficiency is suspected/risk factors for. Stopping: Encourage patients to continue medication, unless deteriorating renal/liver function. Reasons for deprescribing: no harms from stopping suddenly.

Comparative validity between the Canadian and the Dutch norms of the Alberta Infant Motor Scale in a preterm population.

BACKGROUND: Prematurity remains a leading cause of motor developmental delays. The Alberta Infant Motor Scales (AIMS) is a useful tool to easily assess motor development. However, during the last decade, cross-cultural differences have been identified regarding the original AIMS norms. Therefore, the aim of this study is twofold: confirm the validity of the AIMS in a preterm population and compare the new Dutch AIMS norms to the original Canadian ones in our Belgian population. METHOD: Ninety-six preterm infants were assessed simultaneously on the AIMS and on the Bayley Scales of Infant-Toddler Development (Bayley-III) at age 9-14 months. Concurrent validity was evaluated by correlation analysis. Among these, 89 were assessed on the AIMS at age 3-6 months. Clinimetric properties of both AIMS norms were calculated to compare their ability to detect a motor delay on the Bayley-III at age 9-14 months. RESULT: Pearson's coefficient showed an excellent level of correlation between the two scales (r = 0.91). At age 3-6 months, only the 10th Canadian centile showed acceptable properties to predict a significant motor delay. At age 9-14 months, the 5th centile of both norms showed good properties to diagnose a significant motor delay, while only the Canadian norms seems to be sensitive enough to diagnose a mild motor delay. CONCLUSION: The new Dutch norms seem to be less sensitive but more specific than the Canadian ones and therefore require adapted cut-offs to diagnose motor developmental delays in a preterm population.

Plaintiff aims in medical negligence disputes: limitations of an adversarial system.

The adversarial nature of medical negligence litigation is subject to frequent criticism by the media, patient advocates, and scholars. In Ireland, reform of the medical negligence dynamic is often mooted, particularly in response to the high financial costs of this type of litigation; however, change in this area has been slow. Recently, the Irish courts have dealt with a number of high-profile, medical negligence disputes, including claims for those affected by the CervicalCheck controversy, which involved the failure to disclose the results of a retrospective audit to women who had developed cervical cancer. These cases have again highlighted the shortcomings of an adversarial system. This article explores the limitations of the tort system in the context of plaintiff aims in medical negligence disputes, drawing on empirical findings (qualitative interviews with patient support groups and barristers), and the literature. In doing so, the article argues that while financial compensation is necessary and appropriate in cases of medical negligence, the current system fails to recognise the often emotional nature of these claims, and the wider needs and aims of litigants involved in these disputes.

Primary Site Identification of Soft-Tissue Mass: Things to Know in MRI Assessment.

The spectrum of soft-tissue mass is varied, including neoplastic and nonneoplastic/inflammatory lesions. However, soft-tissue tumors have similar imaging findings and, therefore, the diagnosis of soft-tissue mass is challenging. Although careful assessment of the internal characteristics on imaging can often narrow the differential diagnoses, the differential diagnosis may be out of the question if identification of the soft-tissue mass origin is missed. The purpose of this article is to review the imaging findings and the essential anatomy to identify the primary site of the soft-tissue mass, and discuss the associated potential pitfalls. In order not to fall into a pitfall, recognition of characteristic imaging findings indicating the origin of the soft-tissue mass and anatomical knowledge of the normal tissue distribution are necessary. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Comparison of risk scoring systems for upper gastrointestinal bleeding in patients after renal transplantation: a retrospective observational study in Hunan, China.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common complication in renal transplant recipients. However, the risk stratification value of bleeding scoring systems in these patients is unclear, and data regarding risk factors are limited. METHODS: Clinical data of renal transplant recipients in The Third Xiangya hospital were collected. The predictive ability of Glasgow Blatchford score (GBS), pre-endoscopy Rockall score (pRS), and AIMS65 score were assessed by the area under the receiver operating characteristic curve (AUROC). Risk factors of UGIB were analyzed using binary logistic regression analysis. RESULTS: A total of 220 patients were enrolled, of which 55 with UGIB. Endoscopy improved the overall survival rate of patients. Glasgow Blatchford score (AUROC 0.868) performed best at predicting UGIB patients who need intervention or death, with a threshold of 10, sensitivity and specificity were 82.4% and 70%, respectively. In terms of predicting mortality, the GBS score was comparable with AIMS65 score (p = 0.30) and pRS score (p = 0.42). Viral hepatitis, intravenous hormone usage, low platelet count, and low albumin level were significant factors associated with UGIB. CONCLUSIONS: The Glasgow Blatchford score (AUROC 0.868) was best at predicting the need for intervention or death. However, their ability to predict mortality was limited, with AUROC less than 0.8. Our study also identified four independent risk factors for renal transplant recipients with UGIB.

The AIMS home-video method: parental experiences and appraisal for use in neonatal follow-up clinics.

BACKGROUND: In The Netherlands, prematurely born infants and their parents are offered regular developmental check-ups in a hospital setting. In line with providing healthcare at distance, the use of video footage showing the infant's behavior and movements, taken by parents at home and assessed by professionals online, might be a fruitful future practice. The focus of this study was to gain insight into parental experiences with the Alberta Infant Motor Scale home-video method and their appraisal of its applicability for use in an outpatient neonatal follow-up clinic. METHOD: A qualitative descriptive study among parents of healthy extremely or very premature infants (GA 26.2-31.5 weeks) participating in a longitudinal study of motor development between 3-18 months corrected age. Ten semi-structured interviews were conducted and transcribed verbatim. Data was analyzed independently. Inductive content analysis was performed following the process of the AIMS home-video method. RESULTS: Parents appraised the AIMS home-video method as manageable and fun to do. Instructions, instruction film, and checklists were clear. Transferring the video footage from their phone to their computer and uploading it to the web portal was sometimes time-consuming. Parents gained a better awareness of their infant's motor development and found the provided feedback a confirmation of what they already thought about their infant's development and was reassuring that their child was doing well. First-time parents seemed more uncertain and had a greater need for information about (motor) development, but on the other hand, also had confidence in their child. All parents thought that home-videos can be an addition to follow-up visits, but cannot replace (all) visits. It may be an opportunity to reduce the frequency of hospital visits, while still having their infant monitored. CONCLUSION: Parents appraised the AIMS home-video method positively and are of the opinion that home-videos can be of added value in monitoring infants at risk in neonatal follow-up additional to hospital visits. In future research a user-friendly application and/or platform to exchange video footage safely between parents and professionals should be developed with all possible stakeholders involved and implementation should be explored.

Embracing multiple aims in healthcare improvement and innovation.

BACKGROUND: Healthcare and other industries have to manage and coordinate a number of different aims and longer-term ambitions. They must maintain quality, manage costs, support and retain the workforce, manage regulatory demands and consider wider societal objectives. These aims are all legitimate, but they are not necessarily aligned, neither in their time frame nor in their nature. Conflicts between aims have a profound influence on the implementation of safety and quality improvement and wider innovation system change. Healthcare leaders understand that these aims may conflict, but the extent and nature of such conflicts have been underestimated. OBJECTIVE: This paper aims to support medical and nursing leadership and executives in the complex task of managing multiple aims in relation to improvement and innovation. METHODS: We drew on our experience and the wider industrial and healthcare literature to find examples of studies and improvement projects with multiple aims and examples of innovation and change in which conflicting aims were apparent. We sought to identify principles that would enable the management of parallel aims and practical strategies that might facilitate implementation. RESULTS: We argue that almost all improvement and innovation in healthcare should address parallel aims, actively seek to articulate these aims and manage potential conflicts between them. We propose four underlying principles to support a more productive approach to the identification and management of parallel aims: embrace multiple aims, consider both short- and long-term aims and ambitions, consider the wider societal context and appreciate that all changes take place within an evolving, dynamic context. In terms of practical actions, we identified five key strategies: (i) identify and monitor the parallel aims and accept that some will conflict; (ii) slow down to accommodate the natural flexibility of the system; (iii) think both the short term and the long term; (iv) expect and endeavour to anticipate some unintended consequences and (v) resist downgrading the project to partial implementation. CONCLUSIONS: We have argued that most improvement and innovation, unlike controlled trials, should consider multiple aims. We set out some broad principles and practices to reduce conflict and suggest avenues to manage conflicts and support positive synergies. We suggest that if this is not done, conflicts are much more likely to arise, which will be detrimental to the change process. Articulating the multiple aims and actively seeking to manage them in parallel will promote a more flexible and productive approach to innovation and change.

Opal: an implementation science tool for machine learning clinical decision support in anesthesia.

Opal is the first published example of a full-stack platform infrastructure for an implementation science designed for ML in anesthesia that solves the problem of leveraging ML for clinical decision support. Users interact with a secure online Opal web application to select a desired operating room (OR) case cohort for data extraction, visualize datasets with built-in graphing techniques, and run in-client ML or extract data for external use. Opal was used to obtain data from 29,004 unique OR cases from a single academic institution for pre-operative prediction of post-operative acute kidney injury (AKI) based on creatinine KDIGO criteria using predictors which included pre-operative demographic, past medical history, medications, and flowsheet information. To demonstrate utility with unsupervised learning, Opal was also used to extract intra-operative flowsheet data from 2995 unique OR cases and patients were clustered using PCA analysis and k-means clustering. A gradient boosting machine model was developed using an 80/20 train to test ratio and yielded an area under the receiver operating curve (ROC-AUC) of 0.85 with 95% CI [0.80-0.90]. At the default probability decision threshold of 0.5, the model sensitivity was 0.9 and the specificity was 0.8. K-means clustering was performed to partition the cases into two clusters and for hypothesis generation of potential groups of outcomes related to intraoperative vitals. Opal's design has created streamlined ML functionality for researchers and clinicians in the perioperative setting and opens the door for many future clinical applications, including data mining, clinical simulation, high-frequency prediction, and quality improvement.

Anaesthesia personnels' perspectives on digital anaesthesia information management systems - a qualitative study.

BACKGROUND: In Norway, the anaesthesia team normally consists of a nurse anaesthetist and an anaesthetist. Digital anesthesia information management systems (AIMS) that collect patient information directly from the anaesthesia workstation, and transmit the data into documentation systems have recently been implemented in Norway. Earlier studies have indicated that implementation of digital AIMS impacts the clinical workflow patterns and distracts the anaesthesia providers. These studies have mainly had a quantitative design and focused on functionality, installation designs, benefits and challenges associated with implementing and using AIMS. Hence, the aim of this study was to qualitatively explore anaesthesia personnel's perspectives on implementing and using digital AIMS. METHODS: The study had an exploratory and descriptive design. The study was conducted within three non-university hospitals in Southern Norway. Qualitative, individual interviews with nurse anaesthetists (n = 9) and anaesthetists (n = 9) were conducted in the period September to December 2020. Data were analysed using qualitative content analysis according to the recommendations of Graneheim and Lundman. RESULTS: Four categories were identified: 1) Balance between clinical assessment and monitoring, 2) Vigilance in relation to the patient, 3) The nurse-physician collaboration, and 4) Software issues. Participants described that anaesthesia included a continuous balance between clinical assessment and monitoring. They experienced that the digital AIMS had an impact on their vigilance in relation to the patient during anaesthesia. The digital AIMS affected the nurse-physician collaboration. Moreover, participants emphasised a lack of user participation and aspects of user-friendliness regarding the implementation of digital AIMS. CONCLUSION: Digital AIMS impacts vigilance in relation to the patient. Hence, collaboration and acceptance of the mutual responsibility between nurse anaesthetists and anaesthetists for both clinical observation and digital AIMS administration is essential. Anaesthesia personnel should be included in development and implementation processes to facilitate implementation.

The effect of the Ambulatory Integration of the Medical and Social (AIMS) model on health risk and depression.

Social needs are factors for health risk and depression that may negatively impact health outcomes and costly services use. Care management addresses social needs that can reduce health risk and depression. An exploratory study of the 5-step Ambulatory Integration of the Medical and Social Model (AIMS) was conducted to examine the effect of steps completed as part of AIMS on patients' depression and health risk outcomes at 6-months. Results reveal steps central to AIMS are significantly related to lower depression and health risk, suggesting AIMS is a valuable intervention for reducing health risk and depression.

Ancestral genetic legacy of the extant population of Argentina as predicted by autosomal and X-chromosomal DIPs.

Aiming to determine their ancestry diagnostic potential, we selected two sets of nuclear deletion/insertion polymorphisms (DIPs), including 30 located on autosomal chromosomes and 33 on the X chromosome. We analysed over 200 unrelated Argentinean individuals living in urban areas of Argentina. As in most American countries, the extant Argentinean population is the result of tricontinental genetic admixture. The peopling process within the continent was characterised by mating bias involving Native American and enslaved African females and European males. Differential results were detected between autosomal DIPs and X-DIPs. The former showed that the European component was the largest (77.8%), followed by the Native American (17.9%) and African (4.2%) components, in good agreement with the previously published results. In contrast, X-DIPs showed that the European genetic contribution was also predominant but much smaller (52.9%) and considerably larger Native American and African contributions (39.6% and 7.5%, respectively). Genetic analysis revealed continental genetic contributions whose associated phenotypic traits have been mostly lost. The observed differences between the estimated continental genetic contribution proportions based on autosomal DIPs and X-DIPs reflect the effects of autosome and X-chromosome transmission behaviour and their different recombination patterns. This work shows the ability of the tested DIP panels to infer ancestry and confirm mating bias. To the best of our knowledge, this is the first study focusing on ancestry-informative autosomal DIP and X-DIP comparisons performed in a sample representing the entire Argentinean population.

Differences in emergency endoscopy outcomes according to gastrointestinal bleeding location.

BACKGROUND AND AIM: With recent technological advances in the field of endoscopic hemostasis, the prognosis of patients with gastrointestinal (GI) bleeding has improved. However, few studies have reported on the clinical course of patients with GI bleeding. This study aimed to evaluate the differences in clinical outcomes of patients with lower GI bleeding (LGIB) compared with upper GI bleeding (UGIB) and the factors related to their prognosis. METHODS: Patients who had undergone emergency endoscopy for GI bleeding were retrospectively reviewed. The severity of GI bleeding was evaluated using the Glasgow-Blatchford (GB), AIMS65, and NOBLADS scores. Patients in whom obvious GI bleeding relapsed and/or iron deficiency anemia persisted after emergency endoscopy were considered to exhibit rebleeding. RESULTS: We reviewed 1697 consecutive patients and divided them into UGIB (1054 patients) and LGIB (643 patients) groups. The proportion of patients with rebleeding was significantly greater in the UGIB group than in the LGIB group; the mortality rate was significantly higher in the UGIB group than in the LGIB group. Multivariate analysis showed that a GB score ≥12 and an AIMS65 score ≥2 were significantly associated with rebleeding in the UGIB group, whereas a NOBLADS score ≥4 was significantly associated with rebleeding in the LGIB group. Notably, the influence of emergency endoscopy differed according to GI bleeding location. CONCLUSIONS: The clinical course was significantly worse in patients with UGIB than in patients with LGIB. The influence of emergency endoscopy differed according to GI bleeding location.

Vaccines and variants: Modelling insights into emerging issues in COVID-19 epidemiology.

Mathematical modelling has played a pivotal role in understanding the epidemiology of and guiding public health responses to the ongoing coronavirus disease of 2019 (COVID-19) pandemic. Here, we review the role of epidemiological models in understanding evolving epidemic characteristics, including the effects of vaccination and Variants of Concern (VoC). We highlight ways in which models continue to provide important insights, including (1) calculating the herd immunity threshold and evaluating its limitations; (2) verifying that nascent vaccines can prevent severe disease, infection, and transmission but may be less efficacious against VoC; (3) determining optimal vaccine allocation strategies under efficacy and supply constraints; and (4) determining that VoC are more transmissible and lethal than previously circulating strains, and that immune escape may jeopardize vaccine-induced herd immunity. Finally, we explore how models can help us anticipate and prepare for future stages of COVID-19 epidemiology (and that of other diseases) through forecasts and scenario projections, given current uncertainties and data limitations.