Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Publisher Correction: Intensive farming drives long-term shifts in avian community composition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Intensive farming drives long-term shifts in avian community composition.

Agricultural practices constitute both the greatest cause of biodiversity loss and the greatest opportunity for conservation1,2, given the shrinking scope of protected areas in many regions. Recent studies have documented the high levels of biodiversity-across many taxa and biomes-that agricultural landscapes can support over the short term1,3,4. However, little is known about the long-term effects of alternative agricultural practices on ecological communities4,5 Here we document changes in bird communities in intensive-agriculture, diversified-agriculture and natural-forest habitats in 4 regions of Costa Rica over a period of 18 years. Long-term directional shifts in bird communities were evident in intensive- and diversified-agricultural habitats, but were strongest in intensive-agricultural habitats, where the number of endemic and International Union for Conservation of Nature (IUCN) Red List species fell over time. All major guilds, including those involved in pest control, pollination and seed dispersal, were affected. Bird communities in intensive-agricultural habitats proved more susceptible to changes in climate, with hotter and drier periods associated with greater changes in community composition in these settings. These findings demonstrate that diversified agriculture can help to alleviate the long-term loss of biodiversity outside natural protected areas1.

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III.

Despite recent advances in single-molecule and structural analysis of condensin activity in vitro, mechanisms of functional condensin loading and loop extrusion that lead to specific chromosomal organization remain unclear. In Saccharomyces cerevisiae, the most prominent condensin loading site is the rDNA locus on chromosome XII, but its repetitiveness deters rigorous analysis of individual genes. An equally prominent non-rDNA condensin site is located on chromosome III (chrIII). It lies in the promoter of a putative non-coding RNA gene called RDT1, which is in a segment of the recombination enhancer (RE) that dictates MATa-specific chrIII organization. Here, we unexpectedly find that condensin is recruited to the RDT1 promoter in MATa cells through hierarchical interactions with Fob1, Tof2, and cohibin (Lrs4/Csm1), a set of nucleolar factors that also recruit condensin to the rDNA. Fob1 directly binds to this locus in vitro, while its binding in vivo depends on an adjacent Mcm1/α2 binding site that provides MATa cell specificity. We also uncover evidence for condensin-driven loop extrusion anchored by Fob1 and cohibin at RDT1 that unidirectionally extends toward MATa on the right arm of chrIII, supporting donor preference during mating-type switching. S. cerevisiae chrIII therefore provides a new platform for the study of programmed condensin-mediated chromosome conformation.

Biodiversity and infrastructure interact to drive tourism to and within Costa Rica.

SignificanceTourism accounts for roughly 10% of global gross domestic product, with nature-based tourism its fastest-growing sector in the past 10 years. Nature-based tourism can theoretically contribute to local and sustainable development by creating attractive livelihoods that support biodiversity conservation, but whether tourists prefer to visit more biodiverse destinations is poorly understood. We examine this question in Costa Rica and find that more biodiverse places tend indeed to attract more tourists, especially where there is infrastructure that makes these places more accessible. Safeguarding terrestrial biodiversity is critical to preserving the substantial economic benefits that countries derive from tourism. Investments in both biodiversity conservation and infrastructure are needed to allow biodiverse countries to rely on tourism for their sustainable development.

The M3 Muscarinic Acetylcholine Receptor Can Signal through Multiple G Protein Families.

The M3 muscarinic acetylcholine receptor (M3R) is a G protein-coupled receptor (GPCR) that regulates important physiologic processes, including vascular tone, bronchoconstriction, and insulin secretion. It is expressed on a wide variety of cell types, including pancreatic beta, smooth muscle, neuronal, and immune cells. Agonist binding to the M3R is thought to initiate intracellular signaling events primarily through the heterotrimeric G protein Gq. However, reports differ on the ability of M3R to couple to other G proteins beyond Gq. Using members from the four primary G protein families (Gq, Gi, Gs, and G13) in radioligand binding, GTP turnover experiments, and cellular signaling assays, including live cell G protein dissociation and second messenger assessment of cAMP and inositol trisphosphate, we show that other G protein families, particularly Gi and Gs, can also interact with the human M3R. We further show that these interactions are productive as assessed by amplification of classic second messenger signaling events. Our findings demonstrate that the M3R is more promiscuous with respect to G protein interactions than previously appreciated. SIGNIFICANCE STATEMENT: The study reveals that the human M3 muscarinic acetylcholine receptor (M3R), known for its pivotal roles in diverse physiological processes, not only activates intracellular signaling via Gq as previously known but also functionally interacts with other G protein families such as Gi and Gs, expanding our understanding of its versatility in mediating cellular responses. These findings signify a broader and more complex regulatory network governed by M3R and have implications for therapeutic targeting.

Contributions of carotid bodies, retrotrapezoid nucleus neurons and preBötzinger complex astrocytes to the CO2 -sensitive drive for breathing.

Current models of respiratory CO2 chemosensitivity are centred around the function of a specific population of neurons residing in the medullary retrotrapezoid nucleus (RTN). However, there is significant evidence suggesting that chemosensitive neurons exist in other brainstem areas, including the rhythm-generating region of the medulla oblongata - the preBötzinger complex (preBötC). There is also evidence that astrocytes, non-neuronal brain cells, contribute to central CO2 chemosensitivity. In this study, we reevaluated the relative contributions of the RTN neurons, the preBötC astrocytes, and the carotid body chemoreceptors in mediating the respiratory responses to CO2 in experimental animals (adult laboratory rats). To block astroglial signalling via exocytotic release of transmitters, preBötC astrocytes were targeted to express the tetanus toxin light chain (TeLC). Bilateral expression of TeLC in preBötC astrocytes was associated with ∼20% and ∼30% reduction of the respiratory response to CO2 in conscious and anaesthetized animals, respectively. Carotid body denervation reduced the CO2 respiratory response by ∼25%. Bilateral inhibition of RTN neurons transduced to express Gi-coupled designer receptors exclusively activated by designer drug (DREADDGi ) by application of clozapine-N-oxide reduced the CO2 response by ∼20% and ∼40% in conscious and anaesthetized rats, respectively. Combined blockade of astroglial signalling in the preBötC, inhibition of RTN neurons and carotid body denervation reduced the CO2 -induced respiratory response by ∼70%. These data further support the hypothesis that the CO2 -sensitive drive to breathe requires inputs from the peripheral chemoreceptors and several central chemoreceptor sites. At the preBötC level, astrocytes modulate the activity of the respiratory network in response to CO2 , either by relaying chemosensory information (i.e. they act as CO2  sensors) or by enhancing the preBötC network excitability to chemosensory inputs. KEY POINTS: This study reevaluated the roles played by the carotid bodies, neurons of the retrotrapezoid nucleus (RTN) and astrocytes of the preBötC in mediating the CO2 -sensitive drive to breathe. The data obtained show that disruption of preBötC astroglial signalling, blockade of inputs from the peripheral chemoreceptors or inhibition of RTN neurons similarly reduce the respiratory response to hypercapnia. These data provide further support for the hypothesis that the CO2 -sensitive drive to breathe is mediated by the inputs from the peripheral chemoreceptors and several central chemoreceptor sites.

The host inflammatory response contributes to disease severity in Crimean-Congo hemorrhagic fever virus infected mice.

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. In cell culture, CCHFV is sensed by the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I) molecule and its adaptor molecule mitochondrial antiviral signaling (MAVS) protein. MAVS initiates both type I interferon (IFN-I) and proinflammatory responses. Here, we studied the role MAVS plays in CCHFV infection in mice in both the presence and absence of IFN-I activity. MAVS-deficient mice were not susceptible to CCHFV infection when IFN-I signaling was active and showed no signs of disease. When IFN-I signaling was blocked by antibody, MAVS-deficient mice lost significant weight, but were uniformly protected from lethal disease, whereas all control mice succumbed to infection. Cytokine activity in the infected MAVS-deficient mice was markedly blunted. Subsequent investigation revealed that CCHFV infected mice lacking TNF-α receptor signaling (TNFA-R-deficient), but not IL-6 or IL-1 activity, had more limited liver injury and were largely protected from lethal outcomes. Treatment of mice with an anti-TNF-α neutralizing antibody also conferred partial protection in a post-virus exposure setting. Additionally, we found that a disease causing, but non-lethal strain of CCHFV produced more blunted inflammatory cytokine responses compared to a lethal strain in mice. Our work reveals that MAVS activation and cytokine production both contribute to CCHFV pathogenesis, potentially identifying new therapeutic targets to treat this disease.

High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

BACKGROUND: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. METHODS: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). CONCLUSION: High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Global suitability and spatial overlap of land-based climate mitigation strategies.

Land-based mitigation strategies (LBMS) are critical to reducing climate change and will require large areas for their implementation. Yet few studies have considered how and where LBMS either compete for land or could be deployed jointly across the Earth's surface. To assess the opportunity costs of scaling up LBMS, we derived high-resolution estimates of the land suitable for 19 different LBMS, including ecosystem maintenance, ecosystem restoration, carbon-smart agricultural and forestry management, and converting land to novel states. Each 1 km resolution map was derived using the Earth's current geographic and biophysical features without socioeconomic constraints. By overlaying these maps, we estimated 8.56 billion hectares theoretically suitable for LBMS across the Earth. This includes 5.20 Bha where only one of the studied strategies is suitable, typically the strategy that involves maintaining the current ecosystem and the carbon it stores. The other 3.36 Bha is suitable for more than one LBMS, framing the choices society has among which LBMS to implement. The majority of these regions of overlapping LBMS include strategies that conflict with one another, such as the conflict between better management of existing land cover types and restoration-based strategies such as reforestation. At the same time, we identified several agricultural management LBMS that were geographically compatible over large areas, including for example, enhanced chemical weathering and improved plantation rotations. Our analysis presents local stakeholders, communities, and governments with the range of LBMS options, and the opportunity costs associated with scaling up any given LBMS to reduce global climate change.

Gender Differences in Defibrillator Practices in Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Disparities remain in survival after out-of-hospital cardiac arrest (OHCA) for women compared to men. Our objective was to evaluate differences in automated external defibrillator (AED) use before Emergency Medical Services (EMS) arrival and time from arrival to initial EMS defibrillation by EMS-assessed gender (women or men). METHODS: This was a secondary analysis of adult non-traumatic, EMS-treated OHCA cases in the Portland Cardiac Arrest Epidemiologic Registry from 2018 to 2021. Emergency Medical Services-witnessed cardiac arrests were excluded and the primary outcomes were pre-EMS AED application and the time from EMS arrival to first defibrillation among patients in a shockable rhythm at first rhythm assessment without pre-EMS AED application. We examined pre-EMS AED application rates overall and separately for law enforcement, in cases where they were on-scene before EMS without a lay bystander AED applied, and lay responders, in cases where law enforcement had not applied an AED. We used multivariable logistic and linear regressions to adjust for potential confounders, including age, arrest location, witness status, bystander CPR, year, and time from dispatch to EMS arrival. We accounted for clustering by county of arrest using a mixed-effects approach. RESULTS: Of the 3,135 adult, EMS-treated non-traumatic OHCAs that were not witnessed by EMS, 3,049 had all variables for analysis, of which 1,011 (33.2%) were women. The adjusted odds (adjusted odds ratio [95% CI]) for any pre-EMS placement of an AED was significantly higher for men compared to women (1.40 [1.05-1.86]). These odds favoring men remained when examining law enforcement AED application (1.89 [1.16-3.07]), but not lay bystander AED application (1.19 [0.83-1.71]). Among patients still in arrest on EMS arrival, with a shockable initial EMS rhythm, and without pre-EMS AED application, the time from EMS arrival on-scene to initial defibrillation was significantly longer for women compared to men (+0.81 min [0.22-1.41 min]). CONCLUSIONS: Women with OHCA received lower rates of pre-EMS AED application and delays in initial EMS defibrillation compared to men.

Utility of end-tidal carbon dioxide to guide resuscitation termination in prolonged out-of-hospital cardiac arrest.

STUDY OBJECTIVE: To evaluate if the change in end-tidal carbon dioxide (ETCO2) over time has improved discriminatory value for determining resuscitation futility compared to a single ETCO2 value in prolonged, refractory non-shockable out-of-hospital cardiac arrest (OHCA). METHODS: This is a retrospective analysis of adult refractory non-shockable, non-traumatic OHCA patients in the Portland Cardiac Arrest Epidemiologic Registry (PDX Epistry) from 2018 to 2021. We defined refractory non-shockable OHCA cases as patients with lack of a shockable rhythm at any time or return of spontaneous circulation at any time prior to 30-min of on-scene resuscitation. We abstracted ETCO2 values first recorded after advanced airway placement and nearest to the 30-min mark of on-scene resuscitation (30 min-ETCO2) from EMS charts. The primary outcome was survival to hospital discharge. We compared 30 min-ETCO2 cutoffs of 10 mmHg and 20 mmHg to the trend (increasing or not) from initial to 30 min-ETCO2 (delta-ETCO2) using sensitivity, specificity, and area under the receiver operating curves (AUROC). RESULTS: Of 3837 adult OHCA, 2850 were initially non-shockable, and there were 617 (16.1%) cases of refractory non-shockable OHCA at 30-min. We excluded 320 cases without at least two ETCO2 recordings in the EMS chart, leaving 297 cases that met inclusion criteria. Of these, 176 (59.3%) were transported and 2 (0.7%) survived to discharge. Using absolute 30 min-ETCO2 cutoffs, both survivors were in the >10 mmHg group (sensitivity 100.0%, specificity 12.5%), whereas only one survivor was identified in the >20 mmHg group (sensitivity 50.0%, specificity 32.5%). Using delta-ETCO2, both survivors were in the increasing ETCO2 group (sensitivity 100.0%, specificity 60.7%). In comparing the two tests that did not misclassify survivors, the AUROC [95% CI] was higher when using delta-ETCO2 (0.803 [0.775-0.831]) compared to an absolute cutoff of 10 mmHg (0.563 [0.544-0.582]). CONCLUSIONS: Nearly one-sixth of EMS-treated adult OHCA patients had refractory non-shockable arrests after at least 30 min of ongoing resuscitation. In this group, the ETCO2 trend following advanced airway placement may be more accurate in guiding termination of resuscitation than an absolute ETCO2 cutoff of 10 or 20 mmHg.

Expression of IL-4 in Tumors: A Safety Surrogate to Predict Cancer Survival Associated With Biologic Therapies.

Interleukin (IL)-4-targeted therapies have revolutionized management of inflammatory dermatoses.

Beyond medical errors: exploring the interpersonal dynamics in physician-patient relationships linked to medico-legal complaints.

BACKGROUND: Previous research suggests that medico-legal complaints often arise from various factors influencing patient dissatisfaction, including medical errors, physician-patient relationships, communication, trust, informed consent, perceived quality of care, and continuity of care. However, these findings are not typically derived from actual patients' cases. This study aims to identify factors impacting the interpersonal dynamics between physicians and patients using real patient cases to understand how patients perceive doctor-patient relational problems that can lead to dissatisfaction and subsequent medico-legal complaints. METHODS: We conducted a retrospective study using data from closed medical regulatory authority complaint cases from the Canadian Medical Protective Association (CMPA) between January 1, 2015, and December 31, 2020. The study population included patients who experienced sepsis and survived, with complaints written by the patients themselves. A multi-stage standardized thematic analysis using Braun and Clarke's approach was employed. Two researchers independently coded the files to ensure the reliability of the identified codes and themes. RESULTS: Thematic analysis of 50 patient cases revealed four broad themes: (1) Ethics in physician's work, (2) Quality of care, (3) Communication, and (4) Healthcare system/policy impacting patient satisfaction. Key sub-themes included confidentiality, honesty, patient involvement, perceived negligence, perceived lack of concern, active engagement and empathy, transparency and clarity, informed consent, respect and demeanor, lack of resources, long wait times, and insufficient time with physicians. CONCLUSIONS: This study identifies and categorizes various factors impacting relational issues between physicians and patients, aiming to increase patient satisfaction and reduce medico-legal cases. Improving physicians' skills in areas such as communication, ethical practices, and patient involvement, as well as addressing systemic problems like long wait times, can enhance the quality of care and reduce medico-legal complaints. Additional training in communication and other skills may help promote stronger relationships between physicians and patients.

From pre-test and post-test probabilities to medical decision making.

BACKGROUND: A central goal of modern evidence-based medicine is the development of simple and easy to use tools that help clinicians integrate quantitative information into medical decision-making. The Bayesian Pre-test/Post-test Probability (BPP) framework is arguably the most well known of such tools and provides a formal approach to quantify diagnostic uncertainty given the result of a medical test or the presence of a clinical sign. Yet, clinical decision-making goes beyond quantifying diagnostic uncertainty and requires that that uncertainty be balanced against the various costs and benefits associated with each possible decision. Despite increasing attention in recent years, simple and flexible approaches to quantitative clinical decision-making have remained elusive. METHODS: We extend the BPP framework using concepts of Bayesian Decision Theory. By integrating cost, we can expand the BPP framework to allow for clinical decision-making. RESULTS: We develop a simple quantitative framework for binary clinical decisions (e.g., action/inaction, treat/no-treat, test/no-test). Let p be the pre-test or post-test probability that a patient has disease. We show that r ∗ = ( 1 - p ) / p represents a critical value called a decision boundary. In terms of the relative cost of under- to over-acting, r ∗ represents the critical value at which action and inaction are equally optimal. We demonstrate how this decision boundary can be used at the bedside through case studies and as a research tool through a reanalysis of a recent study which found widespread misestimation of pre-test and post-test probabilities among clinicians. CONCLUSIONS: Our approach is so simple that it should be thought of as a core, yet previously overlooked, part of the BPP framework. Unlike prior approaches to quantitative clinical decision-making, our approach requires little more than a hand-held calculator, is applicable in almost any setting where the BPP framework can be used, and excels in situations where the costs and benefits associated with a particular decision are patient-specific and difficult to quantify.

Free labial mucocutaneous graft for eyelid reconstruction in four dogs.

PURPOSE: To describe a technique for eyelid margin reconstruction following large mass resection utilizing a free labial mucocutaneous graft. METHODS: Four dogs (4 eyes) underwent en bloc eyelid mass excision under general anesthesia. Measurements were made of the mass followed by free labial mucocutaneous graft retrieval, resection of the mass, and then transplantation of retrieved region of labial mucocutaneous tissue into the resulting defect. RESULTS: Three patients underwent eyelid margin reconstruction with a free labial mucocutaneous graft. One patient received a pedicle advancement graft combined with a free labial mucocutaneous graft. In all cases, a length of 120%-150% of the eyelid defect was retrieved from the oral labia. Postoperative follow-up ranged from 6 weeks to 4 months. All cases had superficial graft necrosis and depigmentation of the donor tissue with total healing time taking up to 8 weeks. All cases had an esthetic and functional reconstruction. CONCLUSIONS: This technique allows reconstruction of the majority of the eyelid margin, greater than that which can be closed primarily. Due to tissue sloughing, the healing time can be extended but cosmetic outcomes are good. Eyelid reconstruction utilizing a free labial graft restored a mucocutaneous margin and recreated a functional eyelid, thus avoiding trichiasis or secondary keratitis.

Modulation of inspiratory burst duration and frequency by bombesin in vitro.

Mammalian respiratory rhythm-generating circuits in the brainstem are subject to neuromodulation by multiple peptidergic afferent inputs controlling circuit behavior and outputs. Although functionally important, actions of neuropeptide modulators have not been fully characterized. We analyzed at cellular and circuit levels two inspiratory patterns intrinsically generated by the preBötzinger complex (preBötC) and their modulation by the neuropeptides bombesin and substance P (SP) in neonatal rat medullary slices in vitro. We found that, in recordings of hypoglossal nerve and preBötC neuron inspiratory activity, some inspiratory bursts occurring spontaneously under basal conditions have a biphasic shape with longer duration than normal inspiratory bursts and occur at a lower frequency. This biphasic burst pattern has been proposed to represent inspiratory activity underling periodic sighs. Bath-applied bombesin or SP decreased the period and increased the duration of both normal inspiratory and biphasic bursts and their underlying synaptic drives. The ratio of the biphasic long-duration burst period to the normal inspiratory burst period and the ratio of their burst durations remained the same before and after peptidergic modulation. Bombesin increased the frequency of the inspiratory rhythm in a Ca2+-independent manner and the frequency of long-duration bursts in a Ca2+-dependent manner. This finding suggests that period and burst duration coupling are due to intrinsic mechanisms controlling simultaneously timing and burst termination within the inspiratory rhythm-generating network. We propose a model in which signaling cascades activated by bombesin and SP modulate mechanisms controlling inspiratory burst frequency and duration to coordinate preBötC circuit behavioral outputs.

Diagnostic and antibiotic stewardship lessons: an outpatient assessment of symptomatic reflex urinalysis ordering accuracy using an electronic best-practice alert.

BACKGROUND: It is not well known how reliably clinicians order reflex urinalysis to microscopy and culture (rUA-cx) for outpatient urinary tract infection (UTI) workup. Antibiotic appropriateness cannot be fully appreciated until the prevalence of UTIs and asymptomatic bacteriuria (ASB) are realized. OBJECTIVE: This quality improvement study has two major aims, first to determine UTI symptom accuracy for rUA-cx ordering and second, to confirm UTI and ASB cases by integrating rUA-cx and cascaded urinalysis results. Antibiotic utilization and diagnostic coding were secondarily linked to UTIs and ASB. METHODS: An electronic best-practice alert informed the ordering of two rUA-cx options: symptomatic- rUA-cx specifically for dysuria, frequency, urgency, costovertebral pain, suprapubic pain or fever versus non-specific-rUA-cx for vague complaints. UTI symptoms were verified by chart review. Confirmed UTI was defined as a significant culture with UTI symptoms and ASB as a significant culture without UTI symptoms. RESULTS: rUA-cx (2065) were prospectively collected over 6 months from female patients at risk for uncomplicated UTIs. Symptomatic-rUA-cx and non-specific-rUA-cx were associated with UTI symptoms for 53% (809/1527) and 20% (107/538), respectively. Overall, 44% (916/2065) of all rUA-cx had UTI symptoms. rUA-cx were overordered by a factor of 9 (2065/225) for every confirmed UTI. The UTI-to-ASB relative ratio was 2.6 (225/86). Regarding UTI-relevant antibiotics, 39% (214/553) were appropriately associated with UTI whereas only 22% (74/339) of inappropriate antibiotics were captured by the ASB definition, underestimating the problem 4-fold. CONCLUSIONS: UTI and ASB remain challenging to categorize despite a meticulous method that applied acceptable criteria.

Diversity, distribution, and expression of opsin genes in freshwater lakes.

Microbial rhodopsins are widely distributed in aquatic environments and may significantly contribute to phototrophy and energy budgets in global oceans. However, the study of freshwater rhodopsins has been largely limited. Here, we explored the diversity, ecological distribution, and expression of opsin genes that encode the apoproteins of type I rhodopsins in humic and clearwater lakes with contrasting physicochemical and optical characteristics. Using metagenomes and metagenome-assembled genomes, we recovered opsin genes from a wide range of taxa, mostly predicted to encode green light-absorbing proton pumps. Viral opsin and novel bacterial opsin clades were recovered. Opsin genes occurred more frequently in taxa from clearwater than from humic water, and opsins in some taxa have nontypical ion-pumping motifs that might be associated with physicochemical conditions of these two freshwater types. Analyses of the surface layer of 33 freshwater systems revealed an inverse correlation between opsin gene abundance and lake dissolved organic carbon (DOC). In humic water with high terrestrial DOC and light-absorbing humic substances, opsin gene abundance was low and dramatically declined within the first few meters, whereas the abundance remained relatively high along the bulk water column in clearwater lakes with low DOC, suggesting opsin gene distribution is influenced by lake optical properties and DOC. Gene expression analysis confirmed the significance of rhodopsin-based phototrophy in clearwater lakes and revealed different diel expressional patterns among major phyla. Overall, our analyses revealed freshwater opsin diversity, distribution and expression patterns, and suggested the significance of rhodopsin-based phototrophy in freshwater energy budgets, especially in clearwater lakes.

Highly cascaded first-order sapphire optical fiber Bragg gratings fabricated by a femtosecond laser.

This Letter reports an innovative technique for fabricating large-scale, highly cascaded first-order sapphire optical fiber Bragg gratings (FBGs) using a femtosecond laser-assisted point-by-point inscription method. For the first time, to the best of our knowledge, this study successfully demonstrates a distributed array of 10 FBGs within highly multimode sapphire crystal fiber, made possible by employing a high-power laser technique to generate larger reflectors with a Gaussian intensity profile. These first-order FBGs offer advantages such as enhanced reflectivity, shorter fabrication time, and simplified spectral characteristics, making them easier to interpret compared with high-order FBGs. The FBGs' resilience and effectiveness are analyzed by subjecting them to temperature tests, proving their capacity for accurate temperature monitoring up to 1500°C-a testament to their suitability for harsh environments. This novel approach broadens the scope for sensing and communication applications in sapphire fibers, particularly under challenging conditions. The novelty of our work lies in successfully overcoming the limitations of previous designs by integrating a cascade of 10 FBGs in sapphire fibers, thereby enhancing multiplexing capabilities, minimizing overlapping of FBG peaks, and ensuring reliable temperature monitoring in industries and applications with thermal gradients.