Rebuilding marine life.

Sustainable Development Goal 14 of the United Nations aims to "conserve and sustainably use the oceans, seas and marine resources for sustainable development". Achieving this goal will require rebuilding the marine life-support systems that deliver the many benefits that society receives from a healthy ocean. Here we document the recovery of marine populations, habitats and ecosystems following past conservation interventions. Recovery rates across studies suggest that substantial recovery of the abundance, structure and function of marine life could be achieved by 2050, if major pressures-including climate change-are mitigated. Rebuilding marine life represents a doable Grand Challenge for humanity, an ethical obligation and a smart economic objective to achieve a sustainable future.

Waveguide quantum electrodynamics with superconducting artificial giant atoms.

Models of light-matter interactions in quantum electrodynamics typically invoke the dipole approximation1,2, in which atoms are treated as point-like objects when compared to the wavelength of the electromagnetic modes with which they interact. However, when the ratio between the size of the atom and the mode wavelength is increased, the dipole approximation no longer holds and the atom is referred to as a 'giant atom'2,3. So far, experimental studies with solid-state devices in the giant-atom regime have been limited to superconducting qubits that couple to short-wavelength surface acoustic waves4-10, probing the properties of the atom at only a single frequency. Here we use an alternative architecture that realizes a giant atom by coupling small atoms to a waveguide at multiple, but well separated, discrete locations. This system enables tunable atom-waveguide couplings with large on-off ratios3 and a coupling spectrum that can be engineered by the design of the device. We also demonstrate decoherence-free interactions between multiple giant atoms that are mediated by the quasi-continuous spectrum of modes in the waveguide-an effect that is not achievable using small atoms11. These features allow qubits in this architecture to switch between protected and emissive configurations in situ while retaining qubit-qubit interactions, opening up possibilities for high-fidelity quantum simulations and non-classical itinerant photon generation12,13.

Global warming impairs stock-recruitment dynamics of corals.

Changes in disturbance regimes due to climate change are increasingly challenging the capacity of ecosystems to absorb recurrent shocks and reassemble afterwards, escalating the risk of widespread ecological collapse of current ecosystems and the emergence of novel assemblages1-3. In marine systems, the production of larvae and recruitment of functionally important species are fundamental processes for rebuilding depleted adult populations, maintaining resilience and avoiding regime shifts in the face of rising environmental pressures4,5. Here we document a regional-scale shift in stock-recruitment relationships of corals along the Great Barrier Reef-the world's largest coral reef system-following unprecedented back-to-back mass bleaching events caused by global warming. As a consequence of mass mortality of adult brood stock in 2016 and 2017 owing to heat stress6, the amount of larval recruitment declined in 2018 by 89% compared to historical levels. For the first time, brooding pocilloporids replaced spawning acroporids as the dominant taxon in the depleted recruitment pool. The collapse in stock-recruitment relationships indicates that the low resistance of adult brood stocks to repeated episodes of coral bleaching is inexorably tied to an impaired capacity for recovery, which highlights the multifaceted processes that underlie the global decline of coral reefs. The extent to which the Great Barrier Reef will be able to recover from the collapse in stock-recruitment relationships remains uncertain, given the projected increased frequency of extreme climate events over the next two decades7.

Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

A Decade of Efforts to Add Value to Child Health Research Practices.

OBJECTIVE: To identify practices that add value to improve the design, conduct, and reporting of child health research and reduce research waste. STUDY DESIGN: In order to categorize the contributions of members of Standards for Research (StaR) in Child Health network, we developed a novel Child Health Improving Research Practices (CHIRP) framework comprised of 5 domains meant to counteract avoidable child health research waste and improve quality: 1) address research questions relevant to children, their families, clinicians, and researchers; 2) apply appropriate research design, conduct and analysis; 3) ensure efficient research oversight and regulation; 4) Provide accessible research protocols and reports; and 5) develop unbiased and usable research reports, including 17 responsible research practice recommendations. All child health research relevant publications by the 48 original StaR standards' authors over the last decade were identified, and main topic areas were categorized using this framework. RESULTS: A total of 247 publications were included in the final sample: 100 publications (41%) in domain 1 (3 recommendations), 77 publications (31%) in domain 2 (3), 35 publications (14%) in domain 3 (4), 20 publications (8%) in domain 4 (4), and 15 publications (6%) in domain 5 (3). We identified readily implementable "responsible" research practices to counter child health research waste and improve quality, especially in the areas of patients and families' engagement throughout the research process, developing Core Outcome Sets, and addressing ethics and regulatory oversight issues. CONCLUSION: While most of the practices are readily implementable, increased awareness of methodological issues and wider guideline uptake is needed to improve child health research. The CHIRP Framework can be used to guide responsible research practices that add value to child health research.

Assessment of Usefulness of Randomized Control Trials in Child Health Research Published in 2007 and 2017.

OBJECTIVE: To examine how clinical usefulness in pediatric research with randomized controlled trials (RCTs) has changed over a 10-year period via a research usefulness tool composed of unique clinical usefulness criteria. STUDY DESIGN: We leveraged a pre-existing sample of child health RCTs published in 2007, used by our team in a previous study. Using the same methods, a research librarian executed a literature search in the Cochrane Central Register of Controlled Trials for the 2017 cohort. We included the first 300 eligible citations from the randomly ordered list for each year, creating two cohorts of 300 publications each, 1 in 2007 and 1 in 2017. Each publication was analyzed and data regarding primary and secondary outcomes, as well as 11 unique criteria of clinical usefulness, were extracted. Each publication was then graded using a tool created by our research team. After quality review, statistical analysis was then performed. RESULTS: Six hundred pediatric RCT publications were included in this review. The mean score increased from 6.07 in 2007 to 9.20 in 2017 (P < .001). Usefulness factors that saw the largest increase in reporting were context placement, funding statements, and conflict of interest statements, while patient centeredness, value for money, and raw data availability remained infrequently reported. CONCLUSION: Our results demonstrate that clinical usefulness of pediatric research improved over this 10-year period, but there are still areas that need a great deal of improvement in order to maximize clinical usefulness and reduce research waste.

Evolving Economics: The Erosion of Medicare Reimbursement in Breast Surgery (2003-2023).

INTRODUCTION: Medicare significantly influences reimbursement rates, setting a standard that impacts private insurance policies. Despite declining rates in various specialties, the magnitude of these trends has not been examined in breast surgery. This study examines Medicare reimbursement trends for breast surgery operations. METHODS: Data for 10 breast operations from 2003 to 2023 were collected from the Medicare Physician Fee Look-Up Tool and yearly reimbursement was computed using the conversion factor. The year-to-year percentage change in reimbursement was calculated, and the overall median change was compared with the consumer price index (CPI) for inflation evaluation. All data were adjusted to 2023 United States dollars. The compound annual growth rate (CAGR) was calculated using inflation-adjusted data. RESULTS: Over the study period, reimbursement for the 10 breast operations had a mean unadjusted percentage increase of + 25.17%, while the CPI increased by 69.15% (p < 0.001). However, after adjustment, overall reimbursement decreased by - 20.70%. Only two operations (lumpectomy and simple mastectomy) saw increased inflation-adjusted Medicare reimbursement (+ 0.37% and + 3.58%, respectively). The CAGR was - 1.54% overall but remained positive for the same two operations (+ 0.02% and + 0.18%, respectively). Based on these findings, breast surgeons were estimated to be reimbursed $107,605,444 less in 2023 than if rates had kept pace with inflation over the past decade. CONCLUSION: Inflation-adjusted Medicare reimbursement rates for breast surgeries have declined from 2003 to 2023. This downward trend may strain resources, potentially leading to compromises in care quality. Surgeons, administrators, and policymakers must take proactive measures to address these issues and ensure the ongoing accessibility and quality of breast surgery.

Autophagy in mesenchymal progenitors protects mice against bone marrow failure after severe intermittent stress.

The cellular mechanisms required to ensure homeostasis of the hematopoietic niche and the ability of this niche to support hematopoiesis upon stress remain elusive. We here identify Wnt5a in Osterix+ mesenchymal progenitor and stem cells (MSPCs) as a critical factor for niche-dependent hematopoiesis. Mice lacking Wnt5a in MSPCs suffer from stress-related bone marrow (BM) failure and increased mortality. Niche cells devoid of Wnt5a show defective actin stress fiber orientation due to an elevated activity of the small GTPase CDC42. This results in incorrect positioning of autophagosomes and lysosomes, thus reducing autophagy and increasing oxidative stress. In MSPCs from patients from BM failure states which share features of peripheral cytopenia and hypocellular BM, we find similar defects in actin stress fiber orientation, reduced and incorrect colocalization of autophagosomes and lysosomes, and CDC42 activation. Strikingly, a short pharmacological intervention to attenuate elevated CDC42 activation in vivo in mice prevents defective actin-anchored autophagy in MSPCs, salvages hematopoiesis and protects against lethal cytopenia upon stress. In summary, our study identifies Wnt5a as a restriction factor for niche homeostasis by affecting CDC42-regulated actin stress-fiber orientation and autophagy upon stress. Our data further imply a critical role for autophagy in MSPCs for adequate support of hematopoiesis by the niche upon stress and in human diseases characterized by peripheral cytopenias and hypocellular BM.

Consolidation trends in vascular surgery.

BACKGROUND: Practice consolidation by vertical and horizontal integration is a growing trend in surgery. Practice consolidation has not been previously examined in vascular surgery. METHODS: The Medicare Provider Enrollment, Chain, and Ownership System data were used to identify vascular providers and vascular surgery practices in the United States in 2015 and 2020. Practices were categorized as solo (1 surgeon), small (2), medium (3-5), and large (≥6). The number of providers and the number of practices in each size group were determined. The Hirfendahl-Hirshman index (HHI), a measure of market consolidation, was calculated. Provider count, practice size, and HHI were additionally analyzed by urban and rural regions. All values were calculated for each time point and compared. RESULTS: Vascular providers increased in number from 2929 to 3154 (7.7%) from 2015 to 2020. The number of practices decreased from 1351 to 1090 (19.3%). The number of large practices increased by 49.4%; the number of small or solo practices decreased by 42.1%. The mean HHI increased from 0.486 in 2015 to 0.498 in 2020. Both urban and rural regions had a decrease in solo practices (43.3% and 2.3%, respectively) and an increase in HHI (from 0.499 to 0.509 and 0.793 to 0.818, respectively). All changes were statistically significant. CONCLUSIONS: From 2015 to 2020, there is a trend toward vascular providers working in larger practice groups and a corresponding increase in measures of market consolidation.

Development of opioid-induced hyperalgesia depends on reactive astrocytes controlled by Wnt5a signaling.

Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in both male and female mice. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1ß. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.

Adrenalectomy Outcome Variations Across Different Functional Adrenal Tumors.

INTRODUCTION: Adrenalectomy generally has favorable outcomes. It is unknown if patients with functional adrenal tumors experience different clinical outcomes than those with benign adrenal tumors, due to the presence of comorbid conditions secondary to the functional tumor. We investigated outcomes following open and laparoscopic adrenalectomy for benign nonfunctional (BNF) versus functional adrenal masses. METHODS: Patients undergoing adrenalectomy were identified in the 2015-2020 National Surgical Quality Improvement Program database, then categorized as BNF, hyperaldosteronism, hypercortisolism, and pheochromocytoma. The primary outcome of interest was 30-d morbidity and secondary outcomes included 30-d mortality, 30-d readmission, and postoperative length of stay (LOS). Subgroup analysis was performed based upon surgical approach. Univariate analysis was performed, followed by multivariable logistic regression for individual outcomes that differed significantly between patients with BNF and functional neoplasm, factoring in patient demographics and operative approach with statistical significance on univariate analysis. Descriptive statistics and outcomes were analyzed using Pearson's χ2 test and Mann-Whitney U-test as appropriate. RESULTS: There were 3291 patients with BNF while 484 had hyperaldosteronism, 263 hypercortisolism, and 46 pheochromocytomas. Within the laparoscopic group of 3615 (88.5%) of adrenalectomy patients, compared to BNF patients, patients with hyperaldosteronism had lower rates of postoperative morbidity (1.9% versus 5.2%, P < 0.001) and shorter LOS (1 d, interquartile range (IQR) [1-1] versus 1d IQR [1-2], P = 0.003); these persisted on multivariate analysis (OR 0.32, 95% confidence interval [CI] 0.14-0.74 and odds ratio 0.47, 95% CI 0.36-0.60, P < 0.001). Patients with hypercortisolism had higher morbidity (7.3% versus 5.2%, P < 0.001), 30-d readmission rates (5.3% versus 2.9%, P = 0.042) and longer LOS (2d, IQR [1-3] versus 1d, IQR [1-2, P < 0.001). On multivariate analysis, presence of hypercortisolism was independently associated with increased likelihood of readmission within 30 d (OR 2.20, 95% CI 1.11-2.99, P = 0.012) and longer LOS (>1 d) (OR 1.79, 95% CI 1.33-2.40, P < 0.001). Compared to BNF patients, patients with pheochromocytoma had higher rates of postoperative morbidity (6.2% versus 5.2%, P < 0.001). Within the open group of 469 (11.5% of adrenalectomy patients), there were no statistically significant differences in outcomes between patients with BNF and functional adrenal masses. CONCLUSIONS: Outcomes after adrenalectomy performed for functional neoplasms differ based on surgical indication.

Perioperative Outcomes After Adrenalectomy for Secondary Adrenal Malignancy.

INTRODUCTION: The risk of adverse outcomes after adrenal metastasectomy is not well defined. Knowledge of these risks is essential to guide patient counseling. METHODS: The 2015-2020 National Surgical Quality Improvement Program datasets were combined. Patients who underwent adrenalectomy for secondary adrenal malignancy (SM) and benign nonfunctional (BNF) adrenal neoplasms were identified; BNF neoplasms were chosen as a comparison as functional neoplasms can contribute to comorbidity. Patients who had additional surgery at the time of adrenalectomy were excluded. Patient demographics, comorbidities, perioperative factors, and outcomes were compared between groups. Multivariable logistic regression analysis was performed. RESULTS: Of 3496 adrenalectomy patients, 332 had SM and 3164 had BNF neoplasms. Patients with SM were older (65 versus 54 y) and more often had chronic obstructive pulmonary disease (7.5% versus 4.4%), chronic steroid use (10.5% versus 3.8%), and bleeding disorders (4.5% versus 2.2%) than patients with BNF, respectively (P < 0.01 for all). Laparoscopic adrenalectomy was the most common operative approach for both groups (74.7% versus 88.3%). Rates of mortality, morbidity, reoperation, readmission, and nonhome discharge did not differ significantly between groups. Patients with SM had higher rates of postoperative bleeding than patients with BNF (6.3% versus 2.6%, P < 0.001). This persisted on multivariable regression analysis that adjusted for demographics, comorbidities, and operative approach (odds ratio 2.34, 95% confidence interval 1.19-4.64). CONCLUSIONS: Adrenalectomy for SM is associated with an increased risk of postoperative bleeding compared to adrenalectomy for BNF adrenal neoplasms. Patients with SM that meet criteria for adrenal metastasectomy should be counseled appropriately.

Evaluating Health Literacy Resources for Secondary Hyperparathyroidism in End-Stage Kidney Disease.

INTRODUCTION: Parathyroidectomy is recommended for severe secondary hyperparathyroidism (SHPT) due to end-stage kidney disease (ESKD), but surgery is underutilized. High quality and accessible online health information, recommended to be at a 6th-grade reading level, is vital to improve patient health literacy. This study evaluated available online resources for SHPT from ESKD based on information quality and readability. METHODS: Three search engines were queried using the terms "parathyroidectomy for secondary hyperparathyroidism," "parathyroidectomy kidney/renal failure," "parathyroidectomy dialysis patients," "should I have surgery for hyperparathyroidism due to kidney failure?," and "do I need surgery for hyperparathyroidism due to kidney failure if I do not have symptoms?" Websites were categorized by source and origin. Two independent reviewers determined information quality using JAMA (0-4) and DISCERN (1-5) frameworks, and scores were averaged. Cohen's kappa evaluated inter-rater reliability. Readability was determined using the Flesch Kincaid Reading Ease, Flesch Kincaid Grade Level, and Simple Measure of Gobbledygook tools. Median readability scores were calculated, and corresponding grade level determined. Websites with reading difficulties >6th grade level were calculated. RESULTS: Thirty one (86.1%) websites originated from the U.S., with most from hospital-associated (63.9%) and foundation/advocacy sources (30.6%). The mean JAMA and DISCERN scores for all websites were 1.3 ± 1.4 and 2.6 ± 0.7, respectively. Readability scores ranged from grade level 5-college level, and most websites scored above the recommended 6th grade level. CONCLUSIONS: Patient-oriented websites tailoring SHPT from ESKD are at a reading level higher than recommended, and the quality of information is low. Efforts must be made to improve the accessibility and quality of information for all patients.

A Bilingual Readability Assessment of Online Breast Cancer Screening and Treatment Information.

INTRODUCTION: Presenting health information at a sixth-grade reading level is advised to accommodate the general public's abilities. Breast cancer (BC) is the second-most common malignancy in women, but the readability of online BC information in English and Spanish, the two most commonly spoken languages in the United States, is uncertain. METHODS: Three search engines were queried using: "how to do a breast examination," "when do I need a mammogram," and "what are the treatment options for breast cancer" in English and Spanish. Sixty websites in each language were studied and classified by source type and origin. Three readability frameworks in each language were applied: Flesch Kincaid Reading Ease, Flesch Kincaid Grade Level, and Simple Measure of Gobbledygook (SMOG) for English, and Fernández-Huerta, Spaulding, and Spanish adaptation of SMOG for Spanish. Median readability scores were calculated, and corresponding grade level determined. The percentage of websites requiring reading abilities >sixth grade level was calculated. RESULTS: English-language websites were predominantly hospital-affiliated (43.3%), while Spanish websites predominantly originated from foundation/advocacy sources (43.3%). Reading difficulty varied across languages: English websites ranged from 5th-12th grade (Flesch Kincaid Grade Level/Flesch Kincaid Reading Ease: 78.3%/98.3% above sixth grade), while Spanish websites spanned 4th-10th grade (Spaulding/Fernández-Huerta: 95%/100% above sixth grade). SMOG/Spanish adaptation of SMOG scores showed lower reading difficulty for Spanish, with few websites exceeding sixth grade (1.7% and 0% for English and Spanish, respectively). CONCLUSIONS: Online BC resources have reading difficulty levels that exceed the recommended sixth grade, although these results vary depending on readability framework. Efforts should be made to establish readability standards that can be translated into Spanish to enhance accessibility for this patient population.

Lost in Translation: Multilingual Analysis of Online Breast Cancer Information.

INTRODUCTION: Patients use the internet to learn more about health conditions. Non-English-speaking patients may face additional challenges. The quality of online breast cancer information, the most common cancer in women, is uncertain. This study aims to examine the quality of online breast cancer information for English and non-English-speaking patients. METHODS: Three search engines were queried using the terms: "how to do a breast examination," "when do I need a mammogram," and "what are the treatment options for breast cancer" in English, Spanish, and Chinese. For each language, 60 unique websites were included and classified by type and information source. Two language-fluent reviewers evaluated website quality using the Journal of American Medical Association benchmark criteria (0-4) and the DISCERN tool (1-5), with higher scores representing higher quality. Scores were averaged for each language. Health On the Net code presence was noted. Inter-rater reliability between reviewers was assessed. RESULTS: English and Spanish websites most commonly originated from US sources (92% and 80%, respectively) compared to Chinese websites (33%, P < 0.001). The most common website type was hospital-affiliated for English (43%) and foundation/advocacy for Spanish and Chinese (43% and 45%, respectively). English websites had the highest and Chinese websites the lowest mean the Journal of American Medical Association (2.2 ± 1.4 versus 1.0 ± 0.8, P = 0.002) and DISCERN scores (3.5 ± 0.9 versus 2.3 ± 0.6, P < 0.001). Health On the Net code was present on 16 (8.9%) websites. Inter-rater reliability ranged from moderate to substantial agreement. CONCLUSIONS: The quality of online information on breast cancer across all three languages is poor. Information quality was poorest for Chinese websites. Improvements to enhance the reliability of breast cancer information across languages are needed.

Global warming transforms coral reef assemblages.

Global warming is rapidly emerging as a universal threat to ecological integrity and function, highlighting the urgent need for a better understanding of the impact of heat exposure on the resilience of ecosystems and the people who depend on them 1 . Here we show that in the aftermath of the record-breaking marine heatwave on the Great Barrier Reef in 2016 2 , corals began to die immediately on reefs where the accumulated heat exposure exceeded a critical threshold of degree heating weeks, which was 3-4 °C-weeks. After eight months, an exposure of 6 °C-weeks or more drove an unprecedented, regional-scale shift in the composition of coral assemblages, reflecting markedly divergent responses to heat stress by different taxa. Fast-growing staghorn and tabular corals suffered a catastrophic die-off, transforming the three-dimensionality and ecological functioning of 29% of the 3,863 reefs comprising the world's largest coral reef system. Our study bridges the gap between the theory and practice of assessing the risk of ecosystem collapse, under the emerging framework for the International Union for Conservation of Nature (IUCN) Red List of Ecosystems 3 , by rigorously defining both the initial and collapsed states, identifying the major driver of change, and establishing quantitative collapse thresholds. The increasing prevalence of post-bleaching mass mortality of corals represents a radical shift in the disturbance regimes of tropical reefs, both adding to and far exceeding the influence of recurrent cyclones and other local pulse events, presenting a fundamental challenge to the long-term future of these iconic ecosystems.

Cryo neutron crystallography demonstrates influence of RNA 2'-OH orientation on conformation, sugar pucker and water structure.

The ribose 2'-hydroxyl is the key chemical difference between RNA and DNA and primary source of their divergent structural and functional characteristics. Macromolecular X-ray diffraction experiments typically do not reveal the positions of hydrogen atoms. Thus, standard crystallography cannot determine 2'-OH orientation (H2'-C2'-O2'-HO2' torsion angle) and its potential roles in sculpting the RNA backbone and the expansive fold space. Here, we report the first neutron crystal structure of an RNA, the Escherichia coli rRNA Sarcin-Ricin Loop (SRL). 2'-OD orientations were established for all 27 residues and revealed O-D bonds pointing toward backbone (O3', 13 observations), nucleobase (11) or sugar (3). Most riboses in the SRL stem region show a 2'-OD backbone-orientation. GAGA-tetraloop riboses display a 2'-OD base-orientation. An atypical C2'-endo sugar pucker is strictly correlated with a 2'-OD sugar-orientation. Neutrons reveal the strong preference of the 2'-OH to donate in H-bonds and that 2'-OH orientation affects both backbone geometry and ribose pucker. We discuss 2'-OH and water molecule orientations in the SRL neutron structure and compare with results from a solution phase 10 µs MD simulation. We demonstrate that joint cryo-neutron/X-ray crystallography offers an all-in-one approach to determine the complete structural properties of RNA, i.e. geometry, conformation, protonation state and hydration structure.

Practice variation in urine collection methods among pre-toilet trained children with suspected urinary tract infection: a systematic review.

BACKGROUND: Urinary tract infections (UTIs) are a common cause of acute illness among infants and young children. There are numerous methods for collecting urine in children who are not toilet trained. This review examined practice variation in the urine collection methods for diagnosing UTI in non-toilet-trained children. METHODS: A systematic review was completed by searching MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), PsycInfo (Ovid), CINAHL (EBSCO), and JBI (Ovid) from January 1, 2000 until October 9, 2021 and updated on May 24, 2023. Studies were included if they were conducted in an acute care facility, examined pre-toilet trained children, and compared one urine collection method with another for relevant health care outcomes (such as length of stay in an ED, or re-visits or readmissions to the ED) or provider satisfaction. Two independent reviewers screened the identified articles independently, and those included in the final analysis were assessed for quality and bias using the Newcastle-Ottawa Scale. RESULTS: Overall, 2535 articles were reviewed and 8 studies with a total of 728 children were included in the final analysis. Seven studies investigated the primary outcome of interest, practice variation in urine collection methods to diagnose a UTI. The seven studies that investigated novel methods of urine collection concluded that there were improved health care outcomes compared to conventional methods. Novel methods include emerging methods that are not captured yet captured in clinical practice guidelines including the use of ultrasound guidance to aid existing techniques. Three studies which investigated healthcare provider satisfaction found preference to novel methods of urine collection. CONCLUSIONS: There is significant practice variation in the urine collection methods within and between countries. Further research is needed to better examine practice variation among clinicians and adherence to national organizations and societies guidelines. PROSPERO registration number CRD42021267754.

Variations in definitions used for describing restrictive care practices (seclusion and restraint) in adult mental health inpatient units: a systematic review and content analysis.

PURPOSE: The main purpose of this review was to (1) identify thematic elements within definitions used by recently published literature to describe the constructs of physical/mechanical restraint, seclusion and chemical restraint in adult mental health inpatient units. METHODS: We conducted a comprehensive literature search of six databases (Scopus, MEDLINE, PsycINFO, Web of Science, Embase, and CINAHL-Plus). In this review, we conducted content analysis to synthesize evidence to understand and compare the commonalities and discrepancies in conceptual elements that were incorporated within the definitions of different forms of restrictive care practices. RESULTS: A total of 95 studies that provided definitions for different forms of restrictive care practices [physical/mechanical restraint (n = 72), seclusion (n = 65) and chemical restraint (n = 19)] were included in this review. Significant variations existed in the conceptual domains presented within the applied definitions of physical/mechanical restraint, seclusion, and chemical restraint. Conceptual themes identified in this review were methods of restrictive care practice, reasons and desired outcomes, the extent of patient restriction during restrictive care practice episodes, timing (duration, frequency, and time of the day), the level of patient autonomy, and the personnel implementing these practices. CONCLUSIONS: Inconsistencies in the terminologies and conceptual boundaries used to describe the constructs of different forms of restrictive care practices underscore the need to move forward in endorsing consensus definitions that reflect the diverse perspectives, ensuring clarity and consistency in practice and research. This will assist in validly measuring and comparing the actual trends of restrictive care practice use across different healthcare institutions and jurisdictions.

Prevalence and variability of restrictive care practice use (physical restraint, seclusion and chemical restraint) in adult mental health inpatient settings: A systematic review and meta-analysis.

BACKGROUND: There is a growing consensus to reduce the use of restrictive care practices in mental health settings to minimise the physical and psychological complications for patients. However, data regarding restrictive care practice use and factors contributing to variations in the proportion estimates has not previously been synthesised. AIMS: This study aimed to synthesise evidence on (1) the pooled proportions of physical restraint, seclusion or chemical restraint in adult mental health inpatients and (2) sources of variability in these proportion estimates. METHODS: Studies were identified from Scopus, MEDLINE, PsycINFO, Web of Science, Embase and CINAHL databases following the PRISMA 2020 guidelines. We conducted a meta-analysis of studies published in English language from 1 January 2010 to 15 August 2022. Binomial data were pooled using a random effect model, with 95% confidence intervals. Meta-regression was also computed to identify factors that may contribute to variations in the proportion estimates. RESULTS: A total of 77 studies were included in this meta-analysis. The pooled prevalence of physical restraint, seclusion and chemical restraint was 14.4%, 15.8% and 25.7%, respectively. Data were heterogeneous across studies (I2 > 99%). Reporting practices and geographical locations contributed to the variability in the reported estimates of restrictive care practices, with studies from Asian countries reporting higher proportions. CONCLUSION: There appear differences between geographical locations in the proportion of restrictive practices in mental health inpatients; however, this is complicated by how these prevalence data have been measured and defined. Consistency in the reporting of restrictive care practices in mental health is required to make valid comparisons between geographical regions, policy settings and practice innovations. RELEVANCE TO CLINICAL PRACTICE: Efforts are needed to develop training programmes and policy changes to ensure consistency in defining and reporting of restrictive care practices in mental health facilities. PATIENT/PUBLIC CONTRIBUTION: This is a systematic review that analysed data from previously published studies, and there was no patient/public contribution in this study. PROTOCOL REGISTRATION: The protocol for this review has been registered to PROSPERO: CRD42022335167.