The protein domains of vertebrate species in which selection is more effective have greater intrinsic structural disorder.

The nearly neutral theory of molecular evolution posits variation among species in the effectiveness of selection. In an idealized model, the census population size determines both this minimum magnitude of the selection coefficient required for deleterious variants to be reliably purged, and the amount of neutral diversity. Empirically, an "effective population size" is often estimated from the amount of putatively neutral genetic diversity and is assumed to also capture a species' effectiveness of selection. A potentially more direct measure of the effectiveness of selection is the degree to which selection maintains preferred codons. However, past metrics that compare codon bias across species are confounded by among-species variation in %GC content and/or amino acid composition. Here we propose a new Codon Adaptation Index of Species (CAIS), based on Kullback-Leibler divergence, that corrects for both confounders. We demonstrate the use of CAIS correlations, as well as the Effective Number of Codons, to show that the protein domains of more highly adapted vertebrate species evolve higher intrinsic structural disorder.

Order of amino acid recruitment into the genetic code resolved by Last Universal Common Ancestor's protein domains.

The current "consensus" order in which amino acids were added to the genetic code is based on potentially biased criteria such as absence of sulfur-containing amino acids from the Urey-Miller experiment in which no sulfur was added. Here, we reassess this order by exploiting the fact that proteins that emerged prior to the genetic code's completion are likely enriched in early amino acids and depleted in late amino acids. We identify the most ancient protein-coding sequences born prior to the archaeal-bacterial split. Amino acid usage in protein sequences whose ancestors date back to a single homolog in the Last Universal Common Ancestor (LUCA) largely matches the consensus order. However, our findings indicate that metal-binding (cysteine and histidine) and sulfur-containing (cysteine and methionine) amino acids were added to the genetic code much earlier than previously thought. Surprisingly, even more ancient protein sequences - those that had already diversified into multiple distinct copies in LUCA - show a different pattern to single copy LUCA sequences: significantly less depleted in the late amino acids tryptophan and tyrosine, and enriched rather than depleted in phenylalanine. This is compatible with at least some of these sequences predating the current genetic code. Their distinct enrichment patterns thus provide hints about earlier, alternative genetic codes.

The development of lateral flow devices for urinary biomarkers to assess kidney health.

Serum creatinine levels are insensitive to real-time changes in kidney function or injury. There is a growing interest in assessing kidney injury by measuring biomarkers in body fluid. From our previous studies, we identified and reported three urinary biomarkers namely Uromodulin (UMOD), Osteopontin (OPN), and Interleukin-9 (IL-9) to be associated with kidney health. The availability of a rapid point-of-care test for these urinary biomarkers will potentially accelerate its applicability and accessibility. In this study, we aimed to develop novel lateral flow device (LFD) for UMOD, OPN and IL-9. We tested paired antibodies using Enzyme Linked Immunosorbent Assay wherein we observed functionality only for UMOD and OPN and not for IL-9. A conjugation buffer pH of 7.8 and 8.5 was found suitable at a detection antibody concentration of 15 µg/mL for LFD development. The developed LFDs were found to quantitatively measure UMOD standard (LLOD of 80,000 pg/mL) and OPN standard (LLOD of 8600 pg/mL) respectively. The LFD was also able to measure human urinary UMOD and OPN with a percent CV of 12.12 and 5.23 respectively.

Relationship between serum ß-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation that can progress to inflammation (nonalcoholic steatohepatitis, NASH), and fibrosis. Serum ß-hydroxybutyrate (ß-HB), a product of the ketogenic pathway, is commonly used as a surrogate marker for hepatic fatty acid oxidation (FAO). However, it remains uncertain whether this relationship holds true in the context of NAFLD in humans. We compared fasting serum ß-HB levels with direct measurement of liver mitochondrial palmitate oxidation in humans stratified based on NAFLD severity (n = 142). Patients were stratified based on NAFLD activity score (NAS): NAS = 0 (no disease), NAS = 1-2 (mild), NAS = 3-4 (moderate), and NAS ≥ 5 (advanced). Moderate and advanced NAFLD is associated with reductions in liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), serum ß-HB, but not 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) mRNA, relative to no disease. Worsening liver mitochondrial complete palmitate oxidation corresponded with lower HMGCS2 mRNA but not total (complete + incomplete) palmitate oxidation. Interestingly, we found that liver HMGCS2 mRNA and serum ß-HB correlated with liver mitochondrial ß-hydroxyacyl-CoA dehydrogenase (ß-HAD) activity and CPT1A mRNA. Also, lower mitochondrial mass and markers of mitochondrial turnover positively correlated with lower HMGCS2 in the liver. These data suggest that liver ketogenesis and FAO occur at comparable rates in individuals with NAFLD. Our findings support the utility of serum ß-HB to serve as a marker of liver injury and hepatic FAO in the context of NAFLD.NEW & NOTEWORTHY Serum ß-hydroxybutyrate (ß-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating ß-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum ß-HB. Our work supports serum ß-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

Laparoscopic Conversion of Gastric Bypass to Distal Gastric Bypass for Inadequate Weight Loss.

BACKGROUND: Although uncommon, significant weight recurrence after Roux-en-Y gastric bypass (RYGB) can occur. Options are limited to help patients achieve additional weight loss, and improved techniques for revisional/conversional surgery are needed to achieve optimal outcomes while avoiding significant side effects. Although limited data exist regarding distalization of the Roux limb to achieve a longer biliopancreatic limb leading to some level of malabsorption, we have seen adequate weight loss with minimal significant side effects in patients undergoing this procedure with our approach. An appropriate technical approach to this procedure is important to avoid immediate and long-term complications. METHODS AND RESULTS: We present a video describing our approach to Roux limb distalization for weight gain after gastric bypass, describing our approach for work-up, operative technical pearls, and postoperative monitoring in these patients. A 61 year-old female who initially had good weight loss after RYGB with a body mass index (BMI) nadir of 33, from a preoperative BMI of 53, experienced weight recurrence with her BMI increasing to 48. After preoperative nutritional optimization, dietary counseling, and behavioral counseling, she underwent conversion of RYGB to distalization of Roux limb to create a distal RYGB. She tolerated the procedure well and was discharged on postoperative day 2. At 1-year follow-up, her BMI had decreased to 37 with improvement in dyslipidemia, elevation of liver transaminases, and improvement in hemoglobin A1C. This reflects the impact of this procedure on not only weight loss but also concurrent metabolic diseases associated with obesity. CONCLUSION: We present a case of distalization of a RYGB for weight recurrence, highlighting the technical pearls when performing the procedure. Accurate, intraoperative measurement of the total alimentary limb length is essential to achieve weight loss while minimizing malnutrition and vitamin deficiencies. Assessment of preoperative nutritional levels for evidence of any protein calorie malnutrition is important during surgical decision-making when this conversional metabolic operation is considered. Frequent, postoperative nutritional monitoring is important and occurs with a full bariatric nutritional panel at 3, 6, 9, and 12 months then yearly thereafter. Using our approach, we feel that conversion of RYGB to distalization of Roux limb can lead to improved weight loss without significant side effects.

Neuraminidase-induced externalization of phosphatidylserine activates ADAM17 and impairs insulin signaling in endothelial cells.

Endothelial insulin resistance represents a causal factor in the pathogenesis of type 2 diabetes (T2D) and vascular disease, thus the need to identify molecular mechanisms underlying defects in endothelial insulin signaling. We previously have shown that a disintegrin and metalloproteinase-17 (ADAM17) is increased while insulin receptor α-subunit (IRα) is decreased in the vasculature of patients with T2D, leading to impaired insulin-induced vasodilation. We have also demonstrated that ADAM17 sheddase activity targets IRα; however, the mechanisms driving endothelial ADAM17 activity in T2D are largely unknown. Herein, we report that externalization of phosphatidylserine (PS) to the outer leaflet of the plasma membrane causes ADAM17-mediated shedding of IRα and blunting of insulin signaling in endothelial cells. Furthermore, we demonstrate that endothelial PS externalization is mediated by the phospholipid scramblase anoctamin-6 (ANO6) and that this process can be stimulated by neuraminidase, a soluble enzyme that cleaves sialic acid residues. Of note, we demonstrate that men and women with T2D display increased levels of neuraminidase activity in plasma, relative to age-matched healthy individuals, and this occurs in conjunction with increased ADAM17 activity and impaired leg blood flow responses to endogenous insulin. Collectively, this work reveals the neuraminidase-ANO6-ADAM17 axis as a novel potential target for restoring endothelial insulin sensitivity in T2D.NEW & NOTEWORTHY This work provides the first evidence that neuraminidase, an enzyme increased in the circulation of men and women with type 2 diabetes (T2D), promotes anoctamin-6 (ANO6)-dependent externalization of phosphatidylserine in endothelial cells, which in turn leads to activation of a disintegrin and metalloproteinase-17 (ADAM17) and consequent shedding of the insulin receptor-α from the cell surface. Hence, this work supports that consideration should be given to the neuraminidase-ANO6-ADAM17 axis as a novel potential target for restoring endothelial insulin sensitivity in T2D.

Safety and usability of an endo staple line reinforcement device for pulmonary resections.

Background: Pulmonary resection can present technical challenges for surgeons due to the dissection and closure of tissues, which vary in thickness and elastic properties, occasionally leading to prolonged air leaks. Staple line reinforcements (SLRs) are widely utilized tools for fortifying the stability and integrity of closures in thoracic surgery, however, materials available and ease of use for both surgeon and scrub nurse have been suboptimal. A novel "click-and-go" device pre-loaded with bioabsorbable buttress material was recently developed, the Echelon Endopath SLR (ESLR, Ethicon, Inc., Cincinnati, OH, USA). This prospective study examines the safety and efficacy of this novel device in lung resections. Methods: Adult surgical candidates undergoing primary pulmonary resection (both open and thoracoscopic) where the ESLR would be used were enrolled. Exclusion included reoperation/revision in same anatomical location, hypersensitivity to polyglactin or related products, and body mass index (BMI) ≥46.0 kg/m2. The primary endpoint assessed the incidence of specific device-related adverse events (AEs): prolonged air leak and empyema. Additional endpoints included number of devices replaced during surgery due to slippage or bunching, and surgeon-reported usability responses. Data was summarized for AEs deemed device-related and usability questionnaire responses. Results: A total of 131 subjects were included in the primary endpoint analysis data set with 120 subjects completing the study (91.6%). The mean age at consent was 62.8±12.0 years and 55.7% were female. The most common primary indication for the procedure was malignancy 61.1%, and primary non-malignant lung disease (non-chronic obstructive pulmonary disease) 12.2%. Common procedures performed were wedge resection (58.0%) and lobectomy (34.4%). There were zero reported device-specific/-related AEs which counted toward the primary endpoint. Responses from a usability questionnaire found all surgeons (100.0%) reported the ease of setup was superior to previous devices utilized. Surgeons expressed greater confidence in the buttress material of the ESLR than that of previous SLR devices (strongly agree 88.9%; slightly agree 11.1%). Most also felt that there was less wastage with the click-and-go ESLR (strongly agree 77.8%, slightly agree 11.1%, neutral 11.1%). Conclusions: The ESLR device demonstrates safe and effective performance in this post-market study of specific thoracic procedures. Furthermore, surgeons found this was easier to use.

Duodenal Diverticulitis Following Biliopancreatic Diversion: A Case Report.

Duodenal diverticulitis is a relatively uncommon finding in patients. Treatment of complications of duodenal diverticulitis may be challenging in patients with altered intestinal anatomy such as those with altered anatomy from weight loss procedures involving intestinal bypass. We present a case report describing the management of duodenal diverticulitis following a biliopancreatic diversion, our decision-making process, and our final treatment strategy.

Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) prevalence is rapidly growing, and fatty liver has been found in a quarter of the US population. Increased liver lipids, particularly those derived from the pathway of de novo lipogenesis (DNL), have been identified as a hallmark feature in individuals with high liver fat. This has led to much activity in basic science and drug development in this area. No studies to date have investigated the contribution of DNL across a spectrum of disease, although it is clear that inhibition of DNL has been shown to reduce liver fat. OBJECTIVES: The purpose of this study was to determine whether liver lipid synthesis increases across the continuum of liver injury. METHODS: Individuals (n = 49) consumed deuterated water for 10 d before their scheduled bariatric surgeries to label DNL; blood and liver tissue samples were obtained on the day of the surgery. Liver lipid concentrations were quantitated, and levels of protein and gene expression assessed. RESULTS: Increased liver DNL, measured isotopically, was significantly associated with liver fatty acid synthase protein content (R = 0.470, P = 0.003), total steatosis assessed by histology (R = 0.526, P = 0.0008), and the fraction of DNL fatty acids in plasma very low-density lipoprotein-triacylglycerol (R = 0.747, P < 0.001). Regression analysis revealed a parabolic relationship between fractional liver DNL (percent) and NAFLD activity score (R = 0.538, P = 0.0004). CONCLUSION: These data demonstrate that higher DNL is associated with early to mid stages of liver disease, and this pathway may be an effective target for the treatment of NAFLD and nonalcoholic steatohepatitis. This study was registered at clinicaltrials.gov as NCT03683589.

Concurrent paraesophageal hernia repair in revisional/conversional laparoscopic Roux-en-Y gastric bypass: propensity score-matched analysis of the MBSAQIP database.

BACKGROUND: Patients requiring concurrent paraesophageal hernia repair (CPHR) have been shown to have favorable outcomes in primary bariatric surgery. However, patients requiring revisional or conversional surgery represent a group of patients with higher perioperative risk. Currently, few reports on concurrent paraesophageal hernia repair utilizing the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database are available. The primary aim of this study was to determine perioperative complications associated with CPHR and the Roux-en-Y gastric bypass (RYGB) as a revisional/conversional operation. METHODS: In this study, patients undergoing revisional/conversional RYGB between 2015 and 2020 were accessed via the MBSAQIP database. Patients were categorized based on the presence of a paraesophageal hernia as a concurrent procedure. Patients who underwent revisional/conversional surgery without additional procedures were utilized for controls. A propensity score-matched cohort was generated and E-analysis utilized to assess unmeasured confounding. RESULTS: After exclusions, 35,698 patients were available. Patients receiving CPHR were more likely to be female (90.79% vs 87.37%; p < 0.001) and have increased frequency of gastroesophageal reflux disease (69.20% vs 51.69%; p < 0.001). However, these patients had lower frequencies of sleep apnea (24.12% vs 30.13%; p < 0.001), hypertension requiring medication (38.51% vs 42.59%; p < 0.001), and decreased frequency of hyperlipidemia (19.44% vs 21.60%;p < 0.001). After matching, 6,231 patient pairs were developed and showed that patients undergoing CPHR were at increased risk of readmission (9.44% vs 7.58%; p < 0.001), intervention (3.56% vs 2.79%; p = 0.018), increased requirement for outpatient dehydration treatment (5.87% vs 4.67%;p = 0.004), and overall increased operation time (169.3 min ± 76.0 vs 153.5 ± 73.3; p < 0.001). However, there were no significant increases in the rates of reoperation, death, postoperative leak complications, or bleeding complications after CPHR. CONCLUSION: Patients undergoing revisional/conversional RYGB with CPHR may be at higher risk for a small number of rare postoperative complications. CPHR is a safe procedure in patients undergoing revisional/conversional RYGB in the short-term postoperative period.

Role of hospital strain in determining outcomes for people hospitalised with COVID-19 in England.

BACKGROUND: In England, reported COVID-19 mortality rates increased during winter 2020/21 relative to earlier summer and autumn months. This study aimed to examine the association between COVID-19-related hospital bed-strain during this time and patient outcomes. METHODS: This was a retrospective observational study using Hospital Episode Statistics data for England. All unique patients aged ≥18 years in England with a diagnosis of COVID-19 who had a completed (discharged alive or died in hospital) hospital stay with an admission date between 1 July 2020 and 28 February 2021 were included. Bed-strain was calculated as the number of beds occupied by patients with COVID-19 divided by the maximum COVID-19 bed occupancy during the study period. Bed-strain was categorised into quartiles for modelling. In-hospital mortality was the primary outcome of interest and length of stay a secondary outcome. RESULTS: There were 253 768 unique hospitalised patients with a diagnosis of COVID-19 during a hospital stay. Patient admissions peaked in January 2021 (n=89 047), although the crude mortality rate peaked slightly earlier in December 2020 (26.4%). After adjustment for covariates, the mortality rate in the lowest and highest quartile of bed-strain was 23.6% and 25.3%, respectively (OR 1.13, 95% CI 1.09 to 1.17). For the lowest and the highest quartile of bed-strain, adjusted mean length of stay was 13.2 days and 11.6 days, respectively in survivors and was 16.5 days and 12.6 days, respectively in patients who died in hospital. CONCLUSIONS: High levels of bed-strain were associated with higher in-hospital mortality rates, although the effect was relatively modest and may not fully explain increased mortality rates during winter 2020/21 compared with earlier months. Shorter hospital stay during periods of greater strain may partly reflect changes in patient management over time.

Laparoscopic Conversion of Single-Anastomosis Duodenal Switch (SADI-S) to Roux-en-Y Gastric Bypass With Concurrent Paraesophageal Hernia Repair for Refractory Biliary Reflux and Paraesophageal Hernia.

Single-anastomosis duodenal switch (SADI-S) is effective for weight loss with low reported rates of complications. Bile reflux into the stomach or esophagus is an uncommonly reported complication but can lead to significant symptoms for patients suffering from this complication. Concurrent paraesophageal hernia can exacerbate the symptoms of biliary reflux gastritis. We present a case report describing the management of biliary reflux gastritis with concurrent paraesophageal hernia, our decision-making process, and technical pearls and possible pitfalls.

Western diet contributes to the pathogenesis of non-alcoholic steatohepatitis in male mice via remodeling gut microbiota and increasing production of 2-oleoylglycerol.

The interplay between western diet and gut microbiota drives the development of non-alcoholic fatty liver disease and its progression to non-alcoholic steatohepatitis. However, the specific microbial and metabolic mediators contributing to non-alcoholic steatohepatitis remain to be identified. Here, a choline-low high-fat and high-sugar diet, representing a typical western diet, named CL-HFS, successfully induces male mouse non-alcoholic steatohepatitis with some features of the human disease, such as hepatic inflammation, steatosis, and fibrosis. Metataxonomic and metabolomic studies identify Blautia producta and 2-oleoylglycerol as clinically relevant bacterial and metabolic mediators contributing to CL-HFS-induced non-alcoholic steatohepatitis. In vivo studies validate that both Blautia producta and 2-oleoylglycerol promote liver inflammation and hepatic fibrosis in normal diet- or CL-HFS-fed mice. Cellular and molecular studies reveal that the GPR119/TAK1/NF-κB/TGF-ß1 signaling pathway mediates 2-oleoylglycerol-induced macrophage priming and subsequent hepatic stellate cell activation. These findings advance our understanding of non-alcoholic steatohepatitis pathogenesis and provide targets for developing microbiome/metabolite-based therapeutic strategies against non-alcoholic steatohepatitis.

Hypoalbuminemia as a risk factor for complications in revisional/conversional bariatric surgery: an MBSAQIP analysis.

BACKGROUND: Hypoalbuminemia (HA) is a risk factor for serious complications after elective bariatric surgery. Patients undergoing revisional/conversional bariatric surgery may represent a higher-risk group who often have underlying co-morbid medical illnesses and more complex surgery. OBJECTIVES: This study investigated the postoperative complications in patients with HA undergoing revisional/conversional bariatric surgery. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), years 2015-2019. METHODS: The MBSAQIP database was used to evaluate patients undergoing non-banding revisional/conversional bariatric surgery between 2015 and 2019. Patients were categorized by serum albumin (≤3.5 g/dL). Variables were assessed via bivariate analysis and multivariable regression. Propensity score matching was conducted to compare gastric bypass (RYGB) to sleeve gastrectomy (VSG). RESULTS: One hundred forty-seven thousand four hundred thirty patients underwent revisional/conversional procedures. After applied exclusions, 58,777 patients were available for analysis. The HA group had a significantly (P < .05) higher prevalence of being black (22.95% versus 17.76%), renal insufficiency (1.08% versus .36%), smoking history (9.47% versus 6.91%), chronic obstructive pulmonary disease (COPD) (2.54% versus 1.33%), and history of deep vein thrombosis (DVT) (4.03% versus 2.3%). Postoperative complications associated with HA included perioperative blood transfusion (3.1% versus 1.27%; P < .001), 30day readmission (10.87 versus 6.77%; P < .001), 30day reoperation (4.9% versus 3.18%; P < .001), and 30day mortality (.40% versus .14%; P < .0001). HA was a significant predictor of 30day readmission in the RYGB versus VSG matched cohort (odds ratio [OR], 1.30; 95% confidence interval [CI], [1.14, 1.48]; P < .001). CONCLUSIONS: HA is a risk factor requiring attention for patients undergoing revisional/conversional bariatric surgery and optimization of nutritional status or medical comorbidities associated with HA prior to bariatric surgery may help avoid postoperative complications.

Data quality and autism: Issues and potential impacts.

INTRODUCTION: Large healthcare datasets can provide insight that has the potential to improve outcomes for patients. However, it is important to understand the strengths and limitations of such datasets so that the insights they provide are accurate and useful. The aim of this study was to identify data inconsistencies within the Hospital Episodes Statistics (HES) dataset for autistic patients and assess potential biases introduced through these inconsistencies and their impact on patient outcomes. The study can only identify inconsistencies in recording of autism diagnosis and not whether the inclusion or exclusion of the autism diagnosis is the error. METHODS: Data were extracted from the HES database for the period 1st April 2013 to 31st March 2021 for patients with a diagnosis of autism. First spells in hospital during the study period were identified for each patient and these were linked to any subsequent spell in hospital for the same patient. Data inconsistencies were recorded where autism was not recorded as a diagnosis in a subsequent spell. Features associated with data inconsistencies were identified using a random forest classifiers and regression modelling. RESULTS: Data were available for 172,324 unique patients who had been recorded as having an autism diagnosis on first admission. In total, 43.7 % of subsequent spells were found to have inconsistencies. The features most strongly associated with inconsistencies included greater age, greater deprivation, longer time since the first spell, change in provider, shorter length of stay, being female and a change in the main specialty description. The random forest algorithm had an area under the receiver operating characteristic curve of 0.864 (95 % CI [0.862 - 0.866]) in predicting a data inconsistency. For patients who died in hospital, inconsistencies in their final spell were significantly associated with being 80 years and over, being female, greater deprivation and use of a palliative care code in the death spell. CONCLUSIONS: Data inconsistencies in the HES database were relatively common in autistic patients and were associated a number of patient and hospital admission characteristics. Such inconsistencies have the potential to distort our understanding of service use in key demographic groups.

Evolution of mitochondrial and nuclear genomes in Pennatulacea.

We examine the phylogeny of sea pens using sequences of whole mitochondrial genomes and the nuclear ribosomal cluster generated through low coverage Illumina sequencing. Taxon sampling includes 30 species in 19 genera representing 13 families. Ancestral state reconstruction shows that most sea pen mitochondrial genomes have the ancestral gene order, and that Pennatulacea with diverse gene orders are found in a single clade. The monophyly of Pennatulidae and Protoptilidae are rejected by both the mitochondrial and nuclear dataset, while the mitochondrial dataset further rejects monophyly of Virgulariidae, and the nuclear dataset rejects monophyly of Kophobelemnidae. We show discordance between nuclear ribosomal gene cluster phylogenies and whole mitochondrial genome phylogenies and highlight key Pennatulacea taxa that could be included in cnidarian genome-wide studies to better resolve the sea pen tree of life. We further illustrate how well frequently sequenced markers capture the overall diversity of the mitochondrial genome and the nuclear ribosomal genes in sea pens.

Through COVID-19 and beyond: developing a multidisciplinary telehealth family intervention in first episode psychosis.

The COVID-19 pandemic presents unique challenges to high quality, safe Early Intervention in Psychosis (EIP) service provision. Due to the necessity to ensure EIP continues despite this, we developed a multidisciplinary, blended, telehealth intervention, incorporating psychoeducation and peer support, for family members of first episode psychosis service users: PERCEPTION. This perspective article aims to: describe PERCEPTION; offer reflections on our experience of delivering it; make recommendations for future research; and synthesise key learning to assist the integration of similar interventions in other EIP services. We provide a descriptive account of PERCEPTION's development and implementation, with reflections from the clinicians involved, on supporting families using this approach. We experienced telehealth as patient-focused, safe, and efficient and believe the intervention's blended nature augmented families' engagement. The approach adopted can assist service providers to attain balance between protecting public health and offering a meaningful, therapeutic intervention to support families in the current epoch.

Frailty, Comorbidity, and Associations With In-Hospital Mortality in Older COVID-19 Patients: Exploratory Study of Administrative Data.

BACKGROUND: Older adults have worse outcomes following hospitalization with COVID-19, but within this group there is substantial variation. Although frailty and comorbidity are key determinants of mortality, it is less clear which specific manifestations of frailty and comorbidity are associated with the worst outcomes. OBJECTIVE: We aimed to identify the key comorbidities and domains of frailty that were associated with in-hospital mortality in older patients with COVID-19 using models developed for machine learning algorithms. METHODS: This was a retrospective study that used the Hospital Episode Statistics administrative data set from March 1, 2020, to February 28, 2021, for hospitalized patients in England aged 65 years or older. The data set was split into separate training (70%), test (15%), and validation (15%) data sets during model development. Global frailty was assessed using the Hospital Frailty Risk Score (HFRS) and specific domains of frailty were identified using the Global Frailty Scale (GFS). Comorbidity was assessed using the Charlson Comorbidity Index (CCI). Additional features employed in the random forest algorithms included age, sex, deprivation, ethnicity, discharge month and year, geographical region, hospital trust, disease severity, and International Statistical Classification of Disease, 10th Edition codes recorded during the admission. Features were selected, preprocessed, and input into a series of random forest classification algorithms developed to identify factors strongly associated with in-hospital mortality. Two models were developed; the first model included the demographic, hospital-related, and disease-related items described above, as well as individual GFS domains and CCI items. The second model was similar to the first but replaced the GFS domains and CCI items with the HFRS as a global measure of frailty. Model performance was assessed using the area under the receiver operating characteristic (AUROC) curve and measures of model accuracy. RESULTS: In total, 215,831 patients were included. The model using the individual GFS domains and CCI items had an AUROC curve for in-hospital mortality of 90% and a predictive accuracy of 83%. The model using the HFRS had similar performance (AUROC curve 90%, predictive accuracy 82%). The most important frailty items in the GFS were dementia/delirium, falls/fractures, and pressure ulcers/weight loss. The most important comorbidity items in the CCI were cancer, heart failure, and renal disease. CONCLUSIONS: The physical manifestations of frailty and comorbidity, particularly a history of cognitive impairment and falls, may be useful in identification of patients who need additional support during hospitalization with COVID-19.

An Open Source Replication of a Winning Recidivism Prediction Model.

We present results of our winning solution to the National Institute of Justice recidivism forecasting challenge. Our team, "MCHawks," placed highly in both terms of accuracy (as measured via the Brier score), as well as the fairness criteria (weighted by differences in false positive rates between White and Black parolees). We used a non-linear machine learning model, XGBoost, although we detail our search of different model specifications, as many different models' predictive performance is very similar. Our solution to balancing false positive rates is trivial; we bias predictions to always be "low risk" so false positive rates for each racial group are zero. We discuss changes to the fairness metric to promote non-trivial solutions. By providing open-source replication materials, it is within the capabilities of others to build just as accurate models without extensive statistical expertise or computational resources.