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Despite recent advances in robotic technology, sewer pipe inspection is still limited to conventional approaches that use cable-tethered robots. Such commercially available tethered robots lack autonomy, and their operation must be manually controlled via their tethered cables. Consequently, they can only travel to a certain distance in pipe, cannot access small-diameter pipes, and their deployment incurs high costs for highly skilled operators. In this paper, we introduce a miniaturised mobile robot for pipe inspection. We present an autonomous control strategy for this robot that is effective, stable, and requires only low-computational resources. The robots used here can access pipes as small as 75 mm in diameter. Due to their small size, low carrying capacity, and limited battery supply, our robots can only carry simple sensors, a small processor, and miniature wheel-legs for locomotion. Yet, our control method is able to compensate for these limitations. We demonstrate fully autonomous robot mobility in a sewer pipe network, without any visual aid or power-hungry image processing. The control algorithm allows the robot to correctly recognise each local network configuration, and to make appropriate decisions accordingly. The control strategy was tested using the physical micro robot in a laboratory pipe network. In both simulation and experiment, the robot autonomously and exhaustively explored an unknown pipe network without missing any pipe section while avoiding obstacles. This is a significant advance towards fully autonomous inspection robot systems for sewer pipe networks.

Myofibromas are mesenchymal tumors showing myofibroblastic differentiation and found most frequently in the head and neck region. While several cases of myofibromas have been reported in adults, they have not been described in long bones of the appendicular skeleton. We describe an otherwise healthy young woman who presented with a progressive incapacitating pain in her right shin. Imaging studies revealed a well-circumscribed osteolytic lesion with slight marginal sclerosis confined to the proximal tibia metaphysis, without a soft tissue component. Surgical intervention was performed and histological examination identified a myofibroma. This case represents an extremely rare occurrence of an intraosseous myofibroma involving a long bone in an adult patient. Although solitary myofibroma is a rare lesion in the skeletal bones of adults we believe it should be included in the differential diagnosis of a solitary lytic mass in bone, especially if it is associated with pain.

This article is the first to explore variations in alcohol, drug overdose, and suicide deaths in the United States by marital status before and after the outbreak of COVID-19 pandemic. Using the Multiple Cause-of-Death file and the American Community Survey (2000–2021), we found the nonmarried exhibit mortality rates 2 to 3 times higher in alcohol and suicide deaths and 4 to 5 times higher in drug-related deaths compared to the married population, net of education. This magnitude of marriage advantage is comparable to educational differences in these deaths. The marriage advantages are more pronounced for males than females (except in suicide, where gender differences are minor) and for White individuals compared to Black and Hispanic individuals. Furthermore, the marriage advantage widened substantially during the COVID-19 pandemic. We advocate for viewing these deaths not only through an economic lens but also as manifestations of “social pathology,” urging consideration within broader societal shifts.

This visualization shows the relationship between completed fertility and education across five decades of cohorts in the United States using data from the General Social Survey. Across these cohorts, the educational gradient of fewer children for those with more education is stronger for women than for men. The gradient has become less steep across cohorts as the gap between people with medium and high levels of education has narrowed. Those without high school degrees have the highest fertility rates at all times, but this group represents a decreasing share of the population as educational levels rise over time. Thus, the educational gradient in completed fertility persists but has become less important for overall fertility patterns.

Abstract Early detection of sepsis is key to ensure timely clinical intervention. Since very few end-to-end pipelines are publicly available, fair comparisons between methodologies are difficult if not impossible. Progress is further limited by discrepancies in the reconstruction of sepsis onset time. This retrospective cohort study highlights the variation in performance of predictive models under three subtly different interpretations of sepsis onset from the sepsis-III definition and compares this against inter-model differences. The models are chosen to cover tree-based, deep learning, and survival analysis methods. Using the MIMIC-III database, between 867 and 2178 intensive care unit admissions with sepsis were identified, depending on the onset definition. We show that model performance can be more sensitive to differences in the definition of sepsis onset than to the model itself. Given a fixed sepsis definition, the best performing method had a gain of 1–5% in the area under the receiver operating characteristic (AUROC). However, the choice of onset time can cause a greater effect, with variation of 0–6% in AUROC. We illustrate that misleading conclusions can be drawn if models are compared without consideration of the sepsis definition used which emphasizes the need for a standardized definition for sepsis onset.

Marriage rates are falling in the United States. The authors ask whether today’s young adults are likely to continue this trend. Using Monitoring the Future Public-Use Cross-Sectional Datasets (1976–2022), this visualization presents U.S. 12th graders’ marriage expectations. It shows declining optimism that they will be “very good” spouses and declining expectations that they will eventually marry. Both trends are prominent in the last 10 years of the survey, and both are more dramatic among young women than among young men. If these trends hold, it may foretell further declines in marriage rates in the coming years.

Background: Incident reporting is widely used in hospitals to improve patient safety, but current reporting systems do not function optimally. The utility of incident reports is limited because hospital staff may not know what to report, may fear retaliation, and may doubt whether administrators will review reports and respond effectively. Methods: This is a clustered randomized controlled trial of the Safety Action Feedback and Engagement (SAFE) Loop, an intervention designed to transform hospital incident reporting systems into effective tools for improving patient safety. The SAFE Loop has six key attributes: obtaining nurses' input about which safety problems to prioritize on their unit; focusing on learning about selected high-priority events; training nurses to write more informative event reports; prompting nurses to report high-priority events; integrating information about events from multiple sources; and providing feedback to nurses on findings and mitigation plans. The study will focus on medication errors and randomize 20 nursing units at a large academic/community hospital in Los Angeles. Outcomes include: (1) incident reporting practices (rates of high-priority reports, contributing factors described in reports), (2) nurses' attitudes toward incident reporting, and (3) rates of high-priority events. Quantitative analyses will compare changes in outcomes pre- and post-implementation between the intervention and control nursing units, and qualitative analyses will explore nurses’ experiences with implementation. Conclusion: If effective, SAFE Loop will have several benefits: increasing nurses’ engagement with reporting, producing more informative reports, enabling safety leaders to understand problems, designing system-based solutions more effectively, and lowering rates of high-priority patient safety events.

Highly multiplexed ddPCR for sensitive nucleic acid quantitation remains challenging due to limited fluorescence channels. Here the authors report quantitative amplicon sequencing (QASeq), a PCR-based molecular barcoding NGS approach which is compatible with high multiplexing.

PurposeTo assess public awareness, interest, and concerns regarding Vuity (1.25% pilocarpine hydrochloride ophthalmic solution), an eye drop for the treatment of presbyopia, based on Google Trends.MethodsWe used Google Trends that provides a relative search volume for queried terms, to evaluate searches for Vuity from June 30, 2021, to June 30, 2022, in the United States. The data for this study were downloaded on June 30, 2022. Main outcome measures were changes in relative search volumes for the terms "Vuity," "Eye drops for reading," "Eye drops for near vision," "Presbyopia," "Pilocarpine," and related popular search terms, such as "Vuity side effects," and "Vuity retinal detachment".ResultsSince the approval of Vuity on October 29, 2021, notable increases in the relative search volumes occurred for Vuity in October 2021, December 2021, and from March to April 2022, which coincided with its approval, availability, and subsequent direct-to-consumer advertising based on positive results of clinical trials. The direct-to-consumer advertising had the greatest impact on the search volume for Vuity. Specific interests included Vuity cost, where to buy it, and its side effects. Retinal detachment was the most highly searched Vuity side effect. Geographic variation was evident, with the relative search volumes highest for "Vuity" in Wyoming, followed by North Dakota.ConclusionGoogle Trends is a useful tool for monitoring increases in public interest in Vuity for presbyopia. Public concerns regarding side effects warrant further real-world investigations of the causal relationship between Vuity and retinal detachment.

Abstract Patients with chronic lymphocytic leukemia (CLL), a B‐cell malignancy characterized by impaired humoral and cellular immunity, are at increased risk of developing cutaneous squamous cell carcinoma (cSCC). Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide and it has been associated with various malignancies, including cSCC. Impaired cell‐mediated immunity is considered a primary risk factor in HPV‐induced cSCC. We examined cSCC lesions from CLL patients with consensus review and HPV genetic analysis to further characterize the relationship between HPV and prevalence of cutaneous malignancy in this population. Eleven patients with CLL contributed 35 cSCCs. Treatment with chemotherapy shortened the latency time to first cSCC. HPV was detected in 54% of the lesions. Among the HPV‐positive cSCC lesions, 84% of the lesions contained alpha‐genus HPV, 42% contained beta‐genus HPV, and 26% of the lesions contained both genera. There was a significant association between HPV‐containing lesions and peritumoral lymphocytic inflammation, suggesting this as a future area for further characterization. The majority of the lesions, including those with alpha‐genus HPV, occurred in sun‐exposed areas, such as the scalp and face. These findings may lead to practice‐changing recommendations for skin cancer, including the use of vaccinations to reduce HPV‐associated skin cancer.

Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives – 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by >30-fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.

The thymus provides a unique microenvironment enabling development and selection of T lymphocytes. Medullary thymic epithelial cells (mTECs) play a pivotal role in this process by facilitating negative selection of self-reactive thymocytes and the generation of Foxp3+ regulatory T cells. Although studies have highlighted the non-canonical nuclear factor κB (NF-κB) pathway as the key regulator of mTEC development, comprehensive understanding of the molecular pathways regulating this process still remains incomplete. Here, we demonstrate that the development of functionally competent mTECs is regulated by the histone deacetylase 3 (Hdac3). Although histone deacetylases are global transcriptional regulators, this effect is highly specific only to Hdac3, as neither Hdac1 nor Hdac2 inactivation caused mTEC ablation. Interestingly, Hdac3 induces an mTEC-specific transcriptional program independently of the previously recognized RANK-NFκB signaling pathway. Thus, our findings uncover yet another layer of complexity of TEC lineage divergence and highlight Hdac3 as a major and specific molecular switch crucial for mTEC differentiation.