Neurological diagnoses in hospitalized COVID-19 patients associated with adverse outcomes: A multinational cohort study.

Few studies examining the patient outcomes of concurrent neurological manifestations during acute COVID-19 leveraged multinational cohorts of adults and children or distinguished between central and peripheral nervous system (CNS vs. PNS) involvement. Using a federated multinational network in which local clinicians and informatics experts curated the electronic health records data, we evaluated the risk of prolonged hospitalization and mortality in hospitalized COVID-19 patients from 21 healthcare systems across 7 countries. For adults, we used a federated learning approach whereby we ran Cox proportional hazard models locally at each healthcare system and performed a meta-analysis on the aggregated results to estimate the overall risk of adverse outcomes across our geographically diverse populations. For children, we reported descriptive statistics separately due to their low frequency of neurological involvement and poor outcomes. Among the 106,229 hospitalized COVID-19 patients (104,031 patients ≥18 years; 2,198 patients <18 years, January 2020-October 2021), 15,101 (14%) had at least one CNS diagnosis, while 2,788 (3%) had at least one PNS diagnosis. After controlling for demographics and pre-existing conditions, adults with CNS involvement had longer hospital stay (11 versus 6 days) and greater risk of (Hazard Ratio = 1.78) and faster time to death (12 versus 24 days) than patients with no neurological condition (NNC) during acute COVID-19 hospitalization. Adults with PNS involvement also had longer hospital stay but lower risk of mortality than the NNC group. Although children had a low frequency of neurological involvement during COVID-19 hospitalization, a substantially higher proportion of children with CNS involvement died compared to those with NNC (6% vs 1%). Overall, patients with concurrent CNS manifestation during acute COVID-19 hospitalization faced greater risks for adverse clinical outcomes than patients without any neurological diagnosis. Our global informatics framework using a federated approach (versus a centralized data collection approach) has utility for clinical discovery beyond COVID-19.

John L. McNulty (1955-2023).

Dr. John L. McNulty, born on January 25, 1955, in Bartlesville, Oklahoma, passed away on October 31, 2023, in Tulsa, Oklahoma, at the age of 68 years. Ever the pragmatist and always bringing a critical mindset to test use, Dr. McNulty coauthored seminal articles demonstrating the absence of predictive bias among African Americans. His commitment to diversity more recently focused on contemporary assessment with transgender and gender-diverse individuals. While Dr. McNulty's empirical work advanced the field of personality and psychopathology, his relationships with colleagues and mentees are his most lasting legacy. Dr. McNulty inspired many while he was here, and his memory will inspire many into the future. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Exploring the Minnesota Multiphasic Personality Inventory (MMPI)-3 in a transgender and gender diverse sample.

Comparisons of transgender and gender diverse (TGD) individuals' mental health functioning with that of cisgender individuals rely almost exclusively on screening measures. The limited research with TGD individuals and omnibus assessment measures has primarily used previous iterations of the Minnesota Multiphasic Personality Inventories (MMPIs). This study sought to examine the psychometric functioning of the MMPI-3 with a TGD community sample (n = 97) and compare mean scores across TGD and cisgender subsamples. We expected MMPI-3 substantive scale reliability to be comparable across all samples and subsamples. Individual MMPI-3 scales were expected to demonstrate appropriate convergent and discriminant validity with relevant criterion measures in the TGD sample. Results generally supported MMPI-3 scale score reliability and validity with TGD individuals. Next, three sets of mean score comparisons were conducted across all MMPI-3 substantive scales: (a) TGD individuals not currently in mental health treatment and the MMPI-3 normative sample, (b) TGD individuals not currently in mental health treatment and TGD individuals currently in mental health treatment, and (c) TGD individuals currently in mental health treatment and an outpatient mental health sample. Fewer differences were found between TGD individuals in our sample who were not currently in mental health treatment and the MMPI-3 normative sample compared to previous work. This initial study indicates that MMPI-3 scales largely have appropriate psychometric properties when administered to a TGD sample and that the test may be helpful in identifying mental health needs of TGD individuals. Needs and directions for further research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

microRNA Expression Dynamics in Culicoides sonorensis Biting Midges Following Blood-Feeding.

Culicoides sonorensis midges vector multiple livestock arboviruses, resulting in significant economic losses worldwide. Due to the tight association between virus transmission, blood feeding, and egg development, understanding midge physiology is paramount to limiting pathogen transmission. Previous studies have demonstrated the importance of small non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), in multiple aspects of vector physiology. These small ncRNAs regulate gene expression at the post-transcriptional level and display differential expression during pathogen infection. Due to the lack of annotated miRNAs in the biting midge and associated expression profiles, we used small RNA-Seq and miRDeep2 analyses to determine the Culicoides miRNAs in whole females and midgut tissues in response to blood feeding. Our analyses revealed 76 miRNAs within C. sonorensis composed of 73 orthologous and three candidate novel miRNAs, as well as conserved miRNA clusters. miRNA conservation suggests an interesting evolutionary relationship between miRNA expression and hematophagy in the infraorder Culicomorpha. We also identified multiple blood meal-regulated and tissue-enriched miRNAs. Lastly, we further identified miRNAs with expression patterns potentially associated with virus infection by probing publicly available datasets. Together, our data provide a foundation for future ncRNA work to untangle the dynamics of gene regulation associated with midge physiology.

INKILN is a Novel Long Noncoding RNA Promoting Vascular Smooth Muscle Inflammation via Scaffolding MKL1 and USP10.

BACKGROUND: Activation of vascular smooth muscle cell (VSMC) inflammation is vital to initiate vascular disease. The role of human-specific long noncoding RNAs in VSMC inflammation is poorly understood. METHODS: Bulk RNA sequencing in differentiated human VSMCs revealed a novel human-specific long noncoding RNA called inflammatory MKL1 (megakaryoblastic leukemia 1) interacting long noncoding RNA (INKILN). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation as well as human atherosclerosis and abdominal aortic aneurysm. The transcriptional regulation of INKILN was verified through luciferase reporter and chromatin immunoprecipitation assays. Loss-of-function and gain-of-function studies and multiple RNA-protein and protein-protein interaction assays were used to uncover a mechanistic role of INKILN in the VSMC proinflammatory gene program. Bacterial artificial chromosome transgenic mice were used to study INKILN expression and function in ligation injury-induced neointimal formation. RESULTS: INKILN expression is downregulated in contractile VSMCs and induced in human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB (nuclear factor kappa B) site within its proximal promoter. INKILN activates proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks interleukin-1ß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1 and the luciferase activity of an NF-κB reporter. Furthermore, INKILN knockdown enhances MKL1 ubiquitination through reduced physical interaction with the deubiquitinating enzyme USP10 (ubiquitin-specific peptidase 10). INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in bacterial artificial chromosome transgenic mice. CONCLUSIONS: These findings elucidate an important pathway of VSMC inflammation involving an INKILN/MKL1/USP10 regulatory axis. Human bacterial artificial chromosome transgenic mice offer a novel and physiologically relevant approach for investigating human-specific long noncoding RNAs under vascular disease conditions.

Removal of polyvinylidene fluoride binder and other organics for enhancing the leaching efficiency of lithium and cobalt from black mass.

The agglomeration and encapsulation of recoverable materials of interest (e.g. metals and graphite) as a result of the presence of polyvinylidene fluoride (PVDF) in spent lithium-ion batteries (LIBs) with mixed chemistries (black mass) lower the extraction efficiency of metals. In this study, organic solvents and alkaline solutions were used as non-toxic reagents to investigate the removal of a PVDF binder from a black mass. The results demonstrated that 33.1%, 31.4%, and 31.4% of the PVDF were removed using dimethylformamide (DMF), dimethylacetamide (DMAc), and dimethyl sulfoxide (DMSO) at 150, 160, and 180 °C, respectively. Under these conditions, the peel-off efficiencies for DMF, DMAc, and DMSO were 92.9%, 85.3%, and approximately 92.9%, respectively. Using tetrabutylammonium bromide (TBAB) as a catalyst and 5 M sodium hydroxide (NaOH) at room temperature (RT- 21 °C-23 °C), 50.3% of PVDF and other organic compounds were eliminated. The removal efficiency was enhanced to approximately 60.5% when the temperature was raised to 80 °C using NaOH. Using 5 M potassium hydroxide at RT in a TBAB-containing solution, ca. 32.8% removal efficiency was obtained; raising the temperature to 80 °C further enhanced the removal efficiency to almost 52.7%. The peel-off efficiency was 100% for both alkaline solutions. Lithium extraction increased from 47.2% to 78.7% following treatment with DMSO and to 90.1% following treatment with NaOH via leaching black mass (2 M sulfuric acid, solid-to-liquid ratio (S/L): 100 g L-1 at 50 °C, for 1 h without a reducing agent) before and after removal of the PVDF binder. Cobalt's recovery went from 28.5% to 61.3% with DMSO treatment to 74.4% with NaOH treatment.

INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10.

Background: Activation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood. Methods: Bulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA called IN flammatory M K L1 I nteracting L ong N oncoding RNA ( INKILN ). INKILN expression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation of INKILN was determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role of INKILN in VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to study INKLIN expression and function in ligation injury-induced neointimal formation. Results: INKILN expression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm. INKILN is transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter. INKILN activates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically, INKILN physically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway. INKILN depletion blocks ILIß-induced nuclear localization of both p65 and MKL1. Knockdown of INKILN abolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further, INKILN knockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10. INKILN is induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice. Conclusions: These findings elucidate an important pathway of VSMC inflammation involving an INKILN /MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.

A bottom-up approach to developing a unified trauma-minority stress model for transgender and gender diverse people.

OBJECTIVE: Transgender and gender diverse (TGD) people are at heightened risk of both Criterion A trauma exposure and other bias-related minority stressors (e.g., discrimination, rejection). In the absence of a unified trauma-minority stress theory, it remains unclear how to best conceptualize psychopathology for people who experience both trauma and minority stress. METHOD: Using a participant-driven q-sort methodology and network analytic approach, we analyzed card sort data from 18 TGD people and 16 providers with expertise in TGD care to derive thematic networks of trauma and minority stress experiences, as they connected to transdiagnostic symptoms (e.g., hyperarousal, avoidance). RESULTS: The TGD participants' resulting network illustrates conceptualizations of identity- and nonidentity-based Criterion A traumas as similar and only related to psychiatric symptoms via the shared connection through other minority stressors. The provider network was more granular, although the general pattern was consistent with TGD participants, demonstrating similar perceptions of how these experiences are associated. CONCLUSIONS: Evidence of inextricable links between trauma and psychiatric symptoms through the conduit of minority stressors lays the groundwork for novel, integrated models of trauma, minority stress, and their transdiagnostic symptom sequelae. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Generation and Comparative Analysis of an Itga8-CreER T2 Mouse with Preferential Activity in Vascular Smooth Muscle Cells.

All current smooth muscle cell (SMC) Cre mice similarly recombine floxed alleles in vascular and visceral SMCs. Here, we present an Itga8-CreER T2 knock-in mouse and compare its activity with a Myh11-CreER T2 mouse. Both Cre drivers demonstrate equivalent recombination in vascular SMCs. However, Myh11-CreER T2 mice, but not Itga8-CreER T2 mice, display high activity in visceral SMC-containing tissues such as intestine, show early tamoxifen-independent activity, and produce high levels of CreERT2 protein. Whereas Myh11-CreER T2 -mediated knockout of serum response factor (Srf) causes a lethal intestinal phenotype precluding analysis of the vasculature, loss of Srf with Itga8-CreER T2 (Srf Itga8 ) yields viable mice with no evidence of intestinal pathology. Male and female Srf Itga8 mice exhibit vascular contractile incompetence, and angiotensin II causes elevated blood pressure in wild type, but not Srf Itga8 , male mice. These findings establish the Itga8-CreER T2 mouse as an alternative to existing SMC Cre mice for unfettered phenotyping of vascular SMCs following selective gene loss.

Machine learning forecasting for COVID-19 pandemic-associated effects on paediatric respiratory infections.

OBJECTIVE: The COVID-19 pandemic and subsequent government restrictions have had a major impact on healthcare services and disease transmission, particularly those associated with acute respiratory infection. This study examined non-identifiable routine electronic patient record data from a specialist children's hospital in England, UK, examining the effect of pandemic mitigation measures on seasonal respiratory infection rates compared with forecasts based on open-source, transferable machine learning models. METHODS: We performed a retrospective longitudinal study of respiratory disorder diagnoses between January 2010 and February 2022. All diagnoses were extracted from routine healthcare activity data and diagnosis rates were calculated for several diagnosis groups. To study changes in diagnoses, seasonal forecast models were fit to prerestriction period data and extrapolated. RESULTS: Based on 144 704 diagnoses from 31 002 patients, all but two diagnosis groups saw a marked reduction in diagnosis rates during restrictions. We observed 91%, 89%, 72% and 63% reductions in peak diagnoses of 'respiratory syncytial virus', 'influenza', 'acute nasopharyngitis' and 'acute bronchiolitis', respectively. The machine learning predictive model calculated that total diagnoses were reduced by up to 73% (z-score: -26) versus expected during restrictions and increased by up to 27% (z-score: 8) postrestrictions. CONCLUSIONS: We demonstrate the association between COVID-19 related restrictions and significant reductions in paediatric seasonal respiratory infections. Moreover, while many infection rates have returned to expected levels postrestrictions, others remain supressed or followed atypical winter trends. This study further demonstrates the applicability and efficacy of routine electronic record data and cross-domain time-series forecasting to model, monitor, analyse and address clinically important issues.

Real-time associations between discrimination, cannabis use, and mood among sexual and gender minority individuals.

OBJECTIVE: Sexual and gender minority (SGM) individuals experience high rates of discrimination, which is associated with increased cannabis use. Studies have also linked daily SGM discrimination to event-based mood states, but none have examined the degree to which cannabis buffers or potentially exacerbates mood in response to discrimination in real time. METHOD: Fifty SGM individuals participated in a 2-week ecological momentary assessment study. Participants completed a baseline assessment and then received six daily prompts assessing SGM discrimination, cannabis use, and current mood. We investigated the immediate associations between SGM discrimination and mood, and how cannabis use differentially moderated these associations. RESULTS: SGM discrimination was associated with increased negative mood and decreased positive mood. Among those who experienced discrimination, individuals who used cannabis reported feeling less anxious and depressed, and happier and more relaxed, in the 2 hr following an SGM discrimination experience compared to those that did not use cannabis. CONCLUSIONS: These findings uncover some of the acute within-day effects of both daily SGM discrimination and cannabis use on mood. These findings build on the current understanding of minority stress, in real time, and suggest avenues for prevention, and intervention efforts to offset risk for psychological distress and cannabis use among SGM individuals who experience minority stress. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Classification Performance of Neural Networks Versus Logistic Regression Models: Evidence From Healthcare Practice.

Machine learning encompasses statistical approaches such as logistic regression (LR) through to more computationally complex models such as neural networks (NN). The aim of this study is to review current published evidence for performance from studies directly comparing logistic regression, and neural network classification approaches in medicine. A literature review was carried out to identify primary research studies which provided information regarding comparative area under the curve (AUC) values for the overall performance of both LR and NN for a defined clinical healthcare-related problem. Following an initial search, articles were reviewed to remove those that did not meet the criteria and performance metrics were extracted from the included articles. Teh initial search revealed 114 articles; 21 studies were included in the study. In 13/21 (62%) of cases, NN had a greater AUC compared to LR, but in most the difference was small and unlikely to be of clinical significance; (unweighted mean difference in AUC 0.03 (95% CI 0-0.06) in favour of NN versus LR. In the majority of cases examined across a range of clinical settings, LR models provide reasonable performance that is only marginally improved using more complex methods such as NN. In many circumstances, the use of a relatively simple LR model is likely to be adequate for real-world needs but in specific circumstances in which large amounts of data are available, and where even small increases in performance would provide significant management value, the application of advanced analytic tools such as NNs may be indicated.

Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO).

INTRODUCTION: Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians' concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid-base abnormalities in children following kidney transplantation compared with current practice.The aim of the Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO) trial was to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte 148 compared with intravenous fluid currently administered. METHODS AND ANALYSIS: PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid-base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect. ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain. TRIAL REGISTRATION NUMBERS: 2019-003025-22 and 16586164.

Of mice and human-specific long noncoding RNAs.

The number of human LncRNAs has now exceeded all known protein-coding genes. Most studies of human LncRNAs have been conducted in cell culture systems where various mechanisms of action have been worked out. On the other hand, efforts to elucidate the function of human LncRNAs in an in vivo setting have been limited. In this brief review, we highlight some strengths and weaknesses of studying human LncRNAs in the mouse. Special consideration is given to bacterial artificial chromosome transgenesis and genome editing. The integration of these technical innovations offers an unprecedented opportunity to complement and extend the expansive literature of cell culture models for the study of human LncRNAs. Two different examples of how BAC transgenesis and genome editing can be leveraged to gain insight into human LncRNA regulation and function in mice are presented: the random integration of a vascular cell-enriched LncRNA and a targeted approach for a new LncRNA immediately upstream of the ACE2 gene, which encodes the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent underlying the coronavirus disease-19 (COVID-19) pandemic.

Hazardous Substance Use Among Sexual and Gender Minority Adults: A Deeper Look into Distal Minority Stressors.

Discrimination and victimization drive health disparities among sexual and gender minority (SGM) individuals, yet little is known about the relative impacts of specific experience types on hazardous substance use. Using data from 704 SGM adults, we examined SGM-related discrimination vs. victimization and specific experiences as predictors of hazardous substance use. SGM-related victimization, not discrimination, predicted hazardous substance use, and SGM-related sexual assault and harassment predicted hazardous alcohol use, although only sexual assault predicted hazardous drug use. These findings implicate lifetime SGM-related victimization, and SGM-related sexual assault and harassment specifically, as key correlates of recent hazardous substance use among SGM adults.

Examining Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scale scores in a transgender and gender diverse sample.

Transgender and gender diverse (TGD) individuals are at increased risk of various forms of psychopathology. Little research has been conducted with broadband measures of psychopathology and TGD individuals. The present study sought to examine how TGD individuals scored on Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scales. This included MMPI-2-RF profiles from 85 TGD individuals; 37 were in mental health treatment and 48 of which were not. This study involved three sets of pairwise comparisons on MMPI-2-RF substantive scales via t-tests: (a) TGD individuals not in treatment versus the MMPI-2-RF normative sample, (v) TGD individuals not in treatment versus TGD individuals in treatment, and (c) TGD individuals in treatment versus a large outpatient clinical sample. Compared to the MMPI-2-RF normative sample, TGD individuals not in treatment scored significantly higher on 31 of the MMPI-2-RF substantive scales. Compared to those TGD individuals not in treatment, those in treatment had significantly higher scores on several MMPI-2-RF scales, primarily those of internalizing psychopathology. In the final comparison between TGD individuals in treatment and an outpatient clinical sample, the TGD individuals had some significantly higher and significantly lower scores on MMPI-2-RF substantive scales. Implications regarding minority stress and the current findings are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impact of the COVID-19 pandemic on radiology appointments in a tertiary children's hospital: a retrospective study.

In this retrospective observational study, we evaluated the impact of the COVID-19 pandemic in London on paediatric radiology activity, as a surrogate of overall hospital activity. We showed a large reduction in overall outpatient imaging activity: 49 250 records occurred in the 371 days post COVID-19 period compared with an expected 67 806 records pre COVID-19 period, representing 18 556 'missed' records. Governmental restrictions were associated with reductions in activity, with the largest reduction in activity during tiers 3 and 4 restrictions. Rescheduling such missed outpatients' appointments represents considerable resource planning and the associated clinical impact on paediatric healthcare remains to be determined.

Infection of Aedes aegypti Mosquitoes with Midgut-Attenuated Sindbis Virus Reduces, but Does Not Eliminate, Disseminated Infection.

Arboviruses are transmitted by specific vectors, and the reasons for this specificity are not fully understood. One contributing factor is the existence of tissue barriers within the vector such as the midgut escape barrier. We used microRNA (miRNA) targeting of Sindbis virus (SINV) to study how replication in midgut cells contributes to overcoming this barrier in the mosquito Aedes aegypti. SINV constructs were designed to be attenuated specifically in midgut cells by inserting binding sites for midgut-specific miRNAs into either the 3' untranslated region (MRE3'miRT) or the structural open reading frame (MRE-ORFmiRT) of the SINV genome. Both miRNA-targeted viruses replicated less efficiently than control viruses in the presence of these miRNAs. When mosquitoes were given infectious blood meals containing miRNA-targeted viruses, only around 20% (MRE3'miRT) or 40% (MRE-ORFmiRT) of mosquitoes developed disseminated infection. In contrast, dissemination occurred in almost all mosquitoes fed control viruses. Deep sequencing of virus populations from individual mosquitoes ruled out selection for mutations in the inserted target sequences as the cause for dissemination in these mosquitoes. In mosquitoes that became infected with miRNA-targeted viruses, titers were equivalent to those of mosquitoes infected with control virus in both the midgut and the carcass, and there was no evidence of a threshold titer necessary for dissemination. Instead, it appeared that if infection was successfully established in the midgut, replication and dissemination were largely normal. Our results support the hypothesis that replication is an important factor in allowing SINV to overcome the midgut escape barrier but hint that other factors are also likely involved. IMPORTANCE When a mosquito ingests an arbovirus during a blood meal, the arbovirus must escape from the midgut of the vector and infect the salivary glands in order to be transmitted to a new host. We used tissue-specific miRNA targeting to examine the requirement for Sindbis virus (SINV) to replicate in midgut epithelium in order to cause disseminated infection in the mosquito Aedes aegypti. Our results indicate that specifically reducing the ability of SINV to replicate in the mosquito midgut reduces its overall ability to establish infection in the mosquito, but if infection is established, replication and dissemination occur normally. These results are consistent with an importance for replication in the midgut epithelium in aiding arboviruses in crossing the midgut barrier.

The design and evaluation of a novel algorithm for automated preference card optimization.

BACKGROUND: Inaccurate surgical preference cards (supply lists) are associated with higher direct costs, waste, and delays. Numerous preference card improvement projects have relied on institution-specific, manual approaches of limited reproducibility. We developed and tested an algorithm to facilitate the first automated, informatics-based, fully reproducible approach. METHODS: The algorithm cross-references the supplies used in each procedure and listed on each preference card and uses a time-series regression to estimate the likelihood that each quantity listed on the preference card is inaccurate. Algorithm performance was evaluated by measuring changes in direct costs between preference cards revised with the algorithm and preference cards that were not revised or revised without use of the algorithm. Results were evaluated with a difference-in-differences (DID) multivariate fixed-effects model of costs during an 8-month pre-intervention and a 15-month post-intervention period. RESULTS: The accuracies of the quantities of 469 155 surgeon-procedure-specific items were estimated. Nurses used these estimates to revise 309 preference cards across eight surgical services corresponding to, respectively, 1777 and 3106 procedures in the pre- and post-intervention periods. The average direct cost of supplies per case decreased by 8.38% ($352, SD $6622) for the intervention group and increased by 13.21% ($405, SD $14 706) for the control group (P < .001). The DID analysis showed significant cost reductions only in the intervention group during the intervention period (P < .001). CONCLUSION: The optimization of preference cards with a variety of institution-specific, manually intensive approaches has led to cost savings. The automated algorithm presented here produced similar results that may be more readily reproducible.