Widespread human exposure to ledanteviruses in Uganda: A population study.

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda.

Anterior Vertebral Body Tethering: A Single-Center Cohort with 4.3 to 7.4 Years of Follow-up.

BACKGROUND: Vertebral body tethering (VBT) is a well-recognized, non-fusion alternative for idiopathic scoliosis in children with growth remaining. To date, there have been almost no published outcome studies with postoperative follow-up of >2 years. We aimed to fill this gap by evaluating mid-term outcomes in our first 31 consecutive patients. METHODS: We retrospectively assessed additional clinical and radiographic data (mean, 5.7 ± 0.7 years) from our first 31 consecutive patients. Assessments included standard deformity measures, skeletal maturity status, and any additional complications (e.g., suspected broken tethers or surgical revisions). Using the same definition of success (i.e., all residual deformities, instrumented or uninstrumented, ≤30° at maturity; no posterior spinal fusion), we revisited the success rate, revision rate, and suspected broken tether rate. RESULTS: Of our first 31 patients treated with VBT, 29 (of whom 28 were non-Hispanic White and 1 was non-Hispanic Asian; 27 were female and 2 were male) returned for additional follow-up. The success rate dropped to 64% with longer follow-up as deformity measures increased, and the revision rate increased to 24% following 2 additional surgical revisions. Four additional suspected broken tethers were identified, for a rate of 55%, with only 1 occurring beyond 4 years. No additional patients had conversion to a posterior spinal fusion. We observed a mean increase of 4° (range, 2° to 8°) in main thoracic deformity measures and 8° (range, 6° to 12°) in thoracolumbar deformity measures. CONCLUSIONS: With >5 years of follow-up, we observed a decrease in postoperative success, as progression of the deformity was observed in most subgroups, and an increase in the revision and suspected broken tether rates. No additional patients had conversion to a posterior spinal fusion, which may indicate long-term survivorship. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Lassa fever research priorities: towards effective medical countermeasures by the end of the decade.

In 2016, WHO designated Lassa fever a priority disease for epidemic preparedness as part of the WHO Blueprint for Action to Prevent Epidemics. One aspect of preparedness is to promote development of effective medical countermeasures (ie, diagnostics, therapeutics, and vaccines) against Lassa fever. Diagnostic testing for Lassa fever has important limitations and key advancements are needed to ensure rapid and accurate diagnosis. Additionally, the only treatment available for Lassa fever is ribavirin, but controversy exists regarding its effectiveness. Finally, no licensed vaccines are available for the prevention and control of Lassa fever. Ongoing epidemiological and behavioural studies are also crucial in providing actionable information for medical countermeasure development, use, and effectiveness in preventing and treating Lassa fever. This Personal View provides current research priorities for development of Lassa fever medical countermeasures based on literature published primarily in the last 5 years and consensus opinion of 20 subject matter experts with broad experience in public health or the development of diagnostics, therapeutics, and vaccines for Lassa fever. These priorities provide an important framework to ensure that Lassa fever medical countermeasures are developed and readily available for use in endemic and at-risk areas by the end of the decade.

A unified metric of human immune health.

Immunological health has been challenging to characterize but could be defined as the absence of immune pathology. While shared features of some immune diseases and the concept of immunologic resilience based on age-independent adaptation to antigenic stimulation have been developed, general metrics of immune health and its utility for assessing clinically healthy individuals remain ill defined. Here we integrated transcriptomics, serum protein, peripheral immune cell frequency and clinical data from 228 patients with 22 monogenic conditions impacting key immunological pathways together with 42 age- and sex-matched healthy controls. Despite the high penetrance of monogenic lesions, differences between individuals in diverse immune parameters tended to dominate over those attributable to disease conditions or medication use. Unsupervised or supervised machine learning independently identified a score that distinguished healthy participants from patients with monogenic diseases, thus suggesting a quantitative immune health metric (IHM). In ten independent datasets, the IHM discriminated healthy from polygenic autoimmune and inflammatory disease states, marked aging in clinically healthy individuals, tracked disease activities and treatment responses in both immunological and nonimmunological diseases, and predicted age-dependent antibody responses to immunizations with different vaccines. This discriminatory power goes beyond that of the classical inflammatory biomarkers C-reactive protein and interleukin-6. Thus, deviations from health in diverse conditions, including aging, have shared systemic immune consequences, and we provide a web platform for calculating the IHM for other datasets, which could empower precision medicine.

How Do I Examine Laryngeal Dystonia?

Laryngeal dystonia is a potentially disabling task specific dystonia primarily affecting speech. The evaluation and diagnosis of laryngeal dystonia remain challenging, and often require a multi-disciplinary approach, involving collaboration among speech language pathologists, neurologists and laryngologists (1-5). It is crucial to correctly differentiate between the types of laryngeal dystonia due to the distinct therapeutic approaches and responses to botulinum toxin therapy or speech therapy. For educational purposes, we have divided laryngeal dystonia into two main types: adductor and abductor dystonia. In this article, we describe a series of examination techniques that can assist movement disorders neurologists diagnosing this condition, and appropriately differentiating the most common forms of laryngeal dystonia.

Preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

BACKGROUND: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions. OBJECTIVES: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up. AUTHORS' CONCLUSIONS: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

Getting from here to there: The contingency of historical evidence and the value of speculation.

Here I look to some work in the historical sciences in order to draw out some of the epistemic benefits of "speculative narratives," which bears on some more general epistemic benefits of speculative reasoning. Due to the contingent nature of much historical evidence, some degree of speculative reasoning is necessary to get the epistemological ball rolling in the historical sciences, and I argue that speculative narratives provide the necessary sort of frameworking apparatus for doing precisely this. I use contemporary work on the first peopling of the Americas (the "Clovis First Debate") for illustration.

Following a strict renal protection protocol in cloacal malformations: A descriptive analysis.

BACKGROUND: In children with cloacal malformations, renal dysfunction is a constant concern, with reported incidence as high as 50%. Multiple factors exist that may impair renal function. Our institution follows a strict renal protection protocol in this population. Incidence of renal dysfunction in these patients is unknown. OBJECTIVE: We aimed to evaluate incidence of renal dysfunction while implementing this protocol in a cohort of children with cloacal malformation. STUDY DESIGN: We reviewed a prospectively collected database of children with cloacal malformations managed at a single institution since implementation of a renal protection protocol. This involves regular laboratory evaluation, appropriate selection of total urogenital mobilization or urogenital separation, proactive imaging in patients with signs of impending renal dysfunction or urinary retention, and early catheterization teaching and implementation if necessary. Glomerular filtration rate (GFR) was calculated with the Schwartz formula and CKD grades assigned per standard definitions. Renal dysfunction was defined as CKD grade 3b or higher, need for renal replacement therapy (RRT) or transplantation. Descriptive statistics were computed. RESULTS: A total of 105 children were managed under this protocol with a median follow-up of 4.2 years [IQR: 2.0-5.9]. Six children (5.7%) had renal dysfunction at most recent follow-up; of these children, only three (2.9%) progressed from normal renal function at initial evaluation to renal dysfunction (Table). No child with normal presenting renal function thus far has progressed to require dialysis or transplantation. DISCUSSION: Previous literature estimated rates of renal dysfunction in cloaca patients as high as 50%; in contrast, we demonstrate a rate of progression to renal dysfunction of 2.9% in girls following a strict renal protection protocol. Most children who developed renal dysfunction had dysfunctional kidneys on presentation. This suggests that preservation of renal function may be possible in early childhood with a strict, multi-disciplinary renal protection protocol. CONCLUSION: In our cohort of patients with cloacal malformations following a strict renal protection protocol, incidence of progressive renal dysfunction is low at 2.9%. Most who go on to renal dysfunction present with impaired renal function.

Considerations for reporting variants in novel candidate genes identified during clinical genomic testing.

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing (ES), the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare disease. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene discovery research programs. Accordingly, clinical laboratories have both the opportunity, and some might argue a responsibility, to contribute to novel gene discovery which should in turn increase the diagnostic yield for many conditions. However, clinical diagnostic laboratories must necessarily balance priorities for throughput, turnaround time, cost efficiency, clinician preferences, and regulatory constraints, and often do not have the infrastructure or resources to effectively participate in either clinical translational or basic genome science research efforts. For these and other reasons, many laboratories have historically refrained from broadly sharing potentially pathogenic variants in novel genes via networks like Matchmaker Exchange, much less reporting such results to ordering providers. Efforts to report such results are further complicated by a lack of guidelines for clinical reporting and interpretation of variants in novel candidate genes. Nevertheless, there are myriad benefits for many stakeholders, including patients/families, clinicians, researchers, if clinical laboratories systematically and routinely identify, share, and report novel candidate genes. To facilitate this change in practice, we developed criteria for triaging, sharing, and reporting novel candidate genes that are most likely to be promptly validated as underlying a Mendelian condition and translated to use in clinical settings.

A scoping review on examination approaches for identifying tactile deficits at the upper extremity in individuals with stroke.

PURPOSE: Accurate perception of tactile stimuli is essential for performing and learning activities of daily living. Through this scoping review, we sought to summarize existing examination approaches for identifying tactile deficits at the upper extremity in individuals with stroke. The goal was to identify current limitations and future research needs for designing more comprehensive examination tools. METHODS: A scoping review was conducted in accordance with the Joanna Briggs Institute methodological framework and the PRISMA for Scoping Reviews (PRISMA-ScR) guidelines. A database search for tactile examination approaches at the upper extremity of individuals with stroke was conducted using Medline (Ovid), The Cochrane Library (Wiley), CINAHL Plus with Full Text (Ebsco), Scopus (Elsevier), PsycInfo (Ebsco), and Proquest Dissertations and Theses Global. Original research and review articles that involved adults (18 years or older) with stroke, and performed tactile examinations at the upper extremity were eligible for inclusion. Data items extracted from the selected articles included: if the examination was behavioral in nature and involved neuroimaging, the extent to which the arm participated during the examination, the number of possible outcomes of the examination, the type(s) of tactile stimulation equipment used, the location(s) along the arm examined, the peripheral nerves targeted for examination, and if any comparison was made with the non-paretic arm or with the arms of individuals who are neurotypical. RESULTS: Twenty-two articles met the inclusion criteria and were accepted in this review. Most examination approaches were behavioral in nature and involved self-reporting of whether a tactile stimulus was felt while the arm remained passive (i.e., no volitional muscle activity). Typically, the number of possible outcomes with these behavioral approaches were limited (2-3), whereas the neuroimaging approaches had many more possible outcomes ( > 15 ). Tactile examinations were conducted mostly at the distal locations along the arm (finger or hand) without targeting any specific peripheral nerve. Although a majority of articles compared paretic and non-paretic arms, most did not compare outcomes to a control group of individuals who are neurotypical. DISCUSSION: Our findings noted that most upper extremity tactile examinations are behavioral approaches, which are subjective in nature, lack adequate resolution, and are insufficient to identify the underlying neural mechanisms of tactile deficits. Also, most examinations are administered at distal locations of the upper extremity when the examinee's arm is relaxed (passive). Further research is needed to develop better tactile examination tools that combine behavioral responses and neurophysiological outcomes, and allow volitional tactile exploration. Approaches that include testing of multiple body locations/nerves along the upper extremity, provide higher resolution of outcomes, and consider normative comparisons with individuals who are neurotypical may provide a more comprehensive understanding of the tactile deficits occurring following a stroke.

Knee Extensor Torque Steadiness and Quadriceps Activation Variability in Collegiate Athletes 4, 6, and 12 Months After ACL Reconstruction.

Background: Quadriceps performance after anterior cruciate ligament reconstruction (ACLR) is typically characterized by peak force/torque, but the ability to generate consistent knee extensor torque may be clinically meaningful. Purpose/Hypothesis: The purpose of this study was to evaluate knee extensor torque steadiness and quadriceps activation variability in collegiate athletes 4 to 12 months after ACLR. It was hypothesized that between-limb asymmetries in torque steadiness and activation variability would be observed and that steadiness would be associated with activation variability and peak knee extensor torque symmetry. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 30 National Collegiate Athletic Association Division I athletes completed maximal voluntary isometric contractions 4, 6, and 12 months after ACLR. Torque and surface electromyography of the superficial quadriceps were recorded. Torque steadiness was calculated as the mean difference between initial and low-pass filtered torque signals and was expressed as a percentage of peak torque. Quadriceps activation variability was calculated similarly and was expressed as a percentage of peak electromyography. Linear mixed models were used to assess change in torque steadiness and activation variability over time. Associations between torque steadiness of the operated limb, activation variability, and quadriceps strength symmetry were evaluated using the Spearman correlation coefficient. Results: Limb-by-time interactions were detected for torque steadiness and activation variability (P < .001), with reductions (improvements) in limb steadiness and activation variability observed with increasing time since surgery. Between-limb differences in torque steadiness and activation variability were observed at 4 and 6 months postoperatively (P < .05). Significant associations between operated limb torque steadiness and quadriceps activation variability were observed at 4 months (P < .001) and 6 months (P < .01). Torque steadiness of the operated limb was associated with peak knee extensor torque symmetry at 4 months (r S = -0.49; P < .01) and 6 months (r S = -0.49; P < .01). Conclusion: In collegiate athletes, impaired knee extensor torque steadiness of the operated limb and associated abnormal quadriceps activation patterns were observed 4 to 12 months after ACLR, and the consistency of knee extensor torque production was associated with greater quadriceps strength asymmetries, particularly 4 to 6 months after surgery. Operated limb torque steadiness and activation variability improved from 4 to 12 months after ACLR. Clinical assessment of knee extensor torque steadiness after ACLR may improve prognosis and specificity of rehabilitation efforts.

PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response.

Primary proteasomopathies have recently emerged as a new class of rare early-onset neurodevelopmental disorders (NDDs) caused by pathogenic variants in the PSMB1, PSMC1, PSMC3, or PSMD12 proteasome genes. Proteasomes are large multi-subunit protein complexes that maintain cellular protein homeostasis by clearing ubiquitin-tagged damaged, misfolded, or unnecessary proteins. In this study, we have identified PSMD11 as an additional proteasome gene in which pathogenic variation is associated with an NDD-causing proteasomopathy. PSMD11 loss-of-function variants caused early-onset syndromic intellectual disability and neurodevelopmental delay with recurrent obesity in 10 unrelated children. Our findings demonstrate that the cognitive impairment observed in these individuals could be recapitulated in Drosophila melanogaster with depletion of the PMSD11 ortholog Rpn6, which compromised reversal learning. Our investigations in subject samples further revealed that PSMD11 loss of function resulted in impaired 26S proteasome assembly and the acquisition of a persistent type I interferon (IFN) gene signature, mediated by the integrated stress response (ISR) protein kinase R (PKR). In summary, these data identify PSMD11 as an additional member of the growing family of genes associated with neurodevelopmental proteasomopathies and provide insights into proteasomal biology in human health.

Evaluation of Alveolar Ridge Dimensions by Socket Preservation Therapy Using a Bone Graft and Platelet-Rich Fibrin: A Randomized Controlled Trial.

BACKGROUND: Following the loss of a tooth, the new edentulous area of the ridge will undergo several adaptive modifications due to changes in function within and surrounding the socket. This bone resorption explains the need for socket preservation techniques in areas of esthetic concerns and functional demands. Demineralized freeze-dried bone allograft (DFDBA) possesses greater osteoinductive potential due to the exposure of bone morphogenetic protein (BMP-3​​​​​​)​and collagen fibrils and can be used efficiently in socket preservation techniques. DFDBA yields better results when combined with an autologous platelet concentrate, such as platelet-rich fibrin. Therefore, we formulated this randomized controlled clinical trial to assess the clinical and radiovisiographical outcomes of platelet-rich fibrin (PRF) and DFDBAs for extraction socket preservation in humans at different time intervals. MATERIALS AND METHODS: This was a randomized controlled trial with 100 people as study subjects, and they were randomly divided into two groups: the test group (DFDBA and PRF placed in the extraction socket) and the control group (natural healing of the extraction socket). Clinical and radiographic evaluation using radiovisiography (RVG) was done at baseline, three-month, and six-month intervals. Cone-beam computed tomography (CBCT) was used at six months to determine the bone density in the test and control groups. RESULTS: When compared from baseline to six months, the percentage change in clinical and RVG measurements for the test group was 15.96% (11.9064 mm) and 16.77% (12.1840 mm), respectively, whereas for the control group, it was 46.09% (14.0396 mm) and 47.61% (14.5716 mm), thus indicating lesser bone resorption in the test group as opposed to the control group. CBCT values also showed greater bone density for the test group (682.3120 HU) than the control group (503.8336 HU). CONCLUSION: This study demonstrates the advantages of DFDBA bone graft with PRF compared to natural healing in achieving socket preservation by maintaining the marginal and buccolingual bone levels.

Genomic imputation of ancient Asian populations contrasts local adaptation in pre- and post-agricultural Japan.

Early modern humans lived as hunter-gatherers for millennia before agriculture, yet the genetic adaptations of these populations remain a mystery. Here, we investigate selection in the ancient hunter-gatherer-fisher Jomon and contrast pre- and post-agricultural adaptation in the Japanese archipelago. Building on the successful validation of imputation with ancient Asian genomes, we identify selection signatures in the Jomon, particularly robust signals from KITLG variants, which may have influenced dark pigmentation evolution. The Jomon lacks well-known adaptive variants (EDAR, ADH1B, and ALDH2), marking their emergence after the advent of farming in the archipelago. Notably, the EDAR and ADH1B variants were prevalent in the archipelago 1,300 years ago, whereas the ALDH2 variant could have emerged later due to its absence in other ancient genomes. Overall, our study underpins local adaptation unique to the Jomon population, which in turn sheds light on post-farming selection that continues to shape contemporary Asian populations.

Quantification of early biofilm growth in microtiter plates through a novel image analysis software.

Given the significant impact of biofilms on human health and material corrosion, research in this field urgently needs more accessible techniques to facilitate the testing of new control agents and general understanding of biofilm biology. Microtiter plates offer a convenient format for standardized evaluations, including high-throughput assays of alternative treatments and molecular modulators. This study introduces a novel Biofilm Analysis Software (BAS) for quantifying biofilms from microtiter plate images. We focused on early biofilm growth stages and compared BAS quantification to common techniques: direct turbidity measurement, intrinsic fluorescence detection linked to pyoverdine production, and standard crystal violet staining which enables image analysis and optical density measurement. We also assessed their sensitivity for detecting subtle growth effects caused by cyclic AMP and gentamicin. Our results show that BAS image analysis is at least as sensitive as the standard method of spectrophotometrically quantifying the crystal violet retained by biofilms. Furthermore, we demonstrated that bacteria adhered after short incubations (from 10 min to 4 h), isolated from planktonic populations by a simple rinse, can be monitored until their growth is detectable by intrinsic fluorescence, BAS analysis, or resolubilized crystal violet. These procedures are widely accessible for many laboratories, including those with limited resources, as they do not require a spectrophotometer or other specialized equipment.

Supporting Emergency Medical Services Clinicians Through Acute and Sustained Crises With Informal Peer Support and Intentional Acts of Kindness: The Emergency Medical Services Code Lavender Program.

OBJECTIVE: Given the recommendations against the use of critical incident stress debriefing, the emergency medical services (EMS) Code Lavender program was created as a mechanism to consistently recognize and reach out to EMS clinicians after acute crisis events, offer nonintrusive informal peer support and acts of kindness, and provide stepwise support via mental health professionals as needed. The study aimed to assess program utilization and evaluate the program's impact on EMS clinicians' perceptions of support and resources available to them after an acute crisis event. METHODS: Anonymous surveys were distributed before program implementation and 18 months later. Program utilization was tracked using REDCap (Vanderbilt University, Nashville, TN). Fisher exact tests and logistic regression were used to analyze the survey results. RESULTS: Within 30 months, 87 referrals were made. Seventy-seven preprogram (59% response rate) and 104 intraprogram (88% response rate) surveys were collected. There were no differences between respondents by sex or role. There were significant improvements in knowing where to go for help (from 40% to 85%, P < .001) and willingness to seek help if needed (from 40% to 59%, P = .02). CONCLUSION: The implementation of an EMS Code Lavender program led to significant increases in EMS clinician self-reported knowledge of where to go and willingness to seek help after acute crisis events.

Observation of topological frequency combs.

On-chip generation of optical frequency combs using nonlinear ring resonators has enabled numerous applications of combs that were otherwise limited to mode-locked lasers. Nevertheless, on-chip frequency combs have relied predominantly on single-ring resonators. In this study, we experimentally demonstrate the generation of a novel class of frequency combs, the topological frequency combs, in a two-dimensional lattice of hundreds of ring resonators that hosts fabrication-robust topological edge states with linear dispersion. By pumping these edge states, we demonstrate the generation of a nested frequency comb that shows oscillation of multiple edge state resonances across ≈40 longitudinal modes and is spatially confined at the lattice edge. Our results provide an opportunity to explore the interplay between topological physics and nonlinear frequency comb generation in a commercially available nanophotonic platform.

Using diffusion models to generate synthetic labeled data for medical image segmentation.

PURPOSE: Medical image analysis has become a prominent area where machine learning has been applied. However, high-quality, publicly available data are limited either due to patient privacy laws or the time and cost required for experts to annotate images. In this retrospective study, we designed and evaluated a pipeline to generate synthetic labeled polyp images for augmenting medical image segmentation models with the aim of reducing this data scarcity. METHODS: We trained diffusion models on the HyperKvasir dataset, comprising 1000 images of polyps in the human GI tract from 2008 to 2016. Qualitative expert review, Fréchet Inception Distance (FID), and Multi-Scale Structural Similarity (MS-SSIM) were tested for evaluation. Additionally, various segmentation models were trained with the generated data and evaluated using Dice score (DS) and Intersection over Union (IoU). RESULTS: Our pipeline produced images more akin to real polyp images based on FID scores. Segmentation model performance also showed improvements over GAN methods when trained entirely, or partially, with synthetic data, despite requiring less compute for training. Moreover, the improvement persists when tested on different datasets, showcasing the transferability of the generated images. CONCLUSIONS: The proposed pipeline produced realistic image and mask pairs which could reduce the need for manual data annotation when performing a machine learning task. We support this use case by showing that the methods proposed in this study enhanced segmentation model performance, as measured by Dice and IoU scores, when trained fully or partially on synthetic data.