Search

To assess the learning efficacy of self-directed virtual reality ultrasound simulators as an alternative to traditional physician-led teaching for cardiac point-of-care ultrasound (POCUS) training. Single blinded (observer), noninferiority, parallel group, randomized controlled study. Tertiary university hospital in Singapore. Forty-three medical students with no prior formal ultrasound training. Participants first completed an e-learning module on basic ultrasonography. Participants' baseline knowledge was subsequently assessed using a multiple-choice question (MCQ) test. Participants were then randomized to either physician-led (PL) teaching or independent learning with a virtual-reality (VR) simulator to learn the 4 cardiac POCUS views. A post-training MCQ test and a practical skills test scored by 2 blinded assessors were conducted. Students repeated the MCQ test and skills test 1 month later. The VR group had higher baseline MCQ scores compared to the PL group (mean, 13.4 v 10.7). Immediately post-training, the PL group had a greater improvement in mean MCQ scores (from baseline) and higher total practical scores compared to the VR group (p = 0.03 and p < 0.01, respectively). At 1 month post-training, the PL group similarly had a greater mean change from baseline MCQ scores, but this difference was not statistically significant (p = 0.12). For practical scores, the VR group scored higher than the PL group, although this difference was not statistically significant (p = 0.06). Our study demonstrates that at 1 month post-training, self-directed VR training was noninferior to PL training. Although differences observed were not significant, there were trends to suggest enhanced retention of knowledge and skills with VR learning. [ABSTRACT FROM AUTHOR]

[Display omitted] The evolution of arterial biomechanics and microstructure with age and disease plays a critical role in understanding the health and function of the cardiovascular system. Accurately capturing these adaptative processes and their effects on the mechanical environment is critical for predicting arterial responses. This challenge is exacerbated by the significant differences between elastic and muscular arteries, which have different structural organizations and functional demands. In this study, we aim to shed light to these adaptive processes by comparing the viscoelastic mechanics of autologous thoracic aortas (TA) and femoropopliteal arteries (FPA) in different age groups. We have extended our fractional viscoelastic framework, originally developed for FPA, to both types of arteries. To evaluate this framework, we analyzed experimental mechanical data from TA and FPA specimens from 21 individuals aged 13 to 73 years. Each specimen was subjected to a multi-ratio biaxial mechanical extension and relaxation test complemented by bidirectional histology to quantify the structural density and microstructural orientations. Our new constitutive model accurately captured the mechanical responses and microstructural differences of the tissues and closely matched the experimentally measured densities. It was found that the viscoelastic properties of collagen and smooth muscle cells (SMCs) in both the FPA and TA remained consistent with age, but the viscoelasticity of the SMCs in the FPA was twice that of the TA. Additionally, changes in collagen nonlinearity with age were similar in both TA and FPA. This model provides valuable insights into arterial mechanophysiology and the effects of pathological conditions on vascular biomechanics. Developing durable treatments for arterial diseases necessitates a deeper understanding of how mechanical properties evolve with age in response to mechanical environments. In this work, we developed a generalized viscoelastic constitutive model for both elastic and muscular arteries and analyzed both the thoracic aorta (TA) and the femoropopliteal artery (FPA) from 21 donors aged 13 to 73. The derived parameters correlate well with histology, allowing further examination of how viscoelasticity evolves with age. Correlation between the TA and FPA of the same donors suggest that the viscoelasticity of the FPA may be influenced by the TA, necessitating more detailed analysis. In summary, our new model proves to be a valuable tool for studying arterial mechanophysiology and exploring pathological impacts. [ABSTRACT FROM AUTHOR]

Total hip arthroplasty (THA) is a common procedure that requires consideration of preexisting comorbidities. Factor V Leiden (FVL), an inherited thrombophilia, is one such condition that predisposes patients to venous thromboembolism (VTE, deep vein thrombosis, and pulmonary embolism). The present study aimed to characterize the risks associated with FVL patients undergoing THA and evaluate the effect of VTE chemoprophylactic agents on these risks. A total of 544,022 adult patients who underwent primary THA for osteoarthritis indications between 2010 and October 2021 were identified in an administrative claims database. Of these, FVL was identified in 1,138 (0.21%). Patients who had and did not have FVL were matched at a 1:4 ratio (1,131 with FVL and 4,519 without FVL) based on age, sex, and Elixhauser comorbidity index. Univariable and multivariable analyses were assessed for 90-day complications. Implant survival at 5 years was assessed and compared with log-rank tests. The relative use of different chemoprophylactic agents, including aspirin, warfarin, heparin, or direct oral anticoagulant (DOAC), was assessed. Bleeding events and VTE were compared for those prescribed either aspirin or warfarin, heparin, or DOAC. A Bonferroni correction was applied. On multivariable analysis, FVL patients were found to have increased odds of 90-day deep vein thrombosis (odds ratio (OR) = 9.20), pulmonary embolism (OR = 6.89), and aggregated severe and all adverse events (OR = 4.74 and 1.98, respectively), but not elevated risk of other perioperative adverse events or 5-year reoperations. More potent chemoprophylactic agents (warfarin, heparin, DOAC) reduced, but did not completely eliminate, the increased VTE risks (without increasing bleeding events). This study quantified the significantly elevated VTE risk associated with FVL patients undergoing THA. The lack of difference in other specific adverse events and 5-year reoperations is reassuring. Clearly, chemoprophylactic agents are important in this population and may need further attention. [ABSTRACT FROM AUTHOR]

Lymphedema microsurgery is an emerging treatment modality, with dissimilar long-term outcomes. One of the main technical challenges in lymphatic microsurgery is the identification and availability of suitable donor vessels for anastomosis. Tissue engineering using biomaterials has demonstrated promise in addressing vessel quality issues in other fields, but its application in microsurgery is still limited. Decellularized cellulose tubes were developed and bioengineered by decellularizing stems of Taraxacum-Ruderalia. The microscopic structure, mechanical properties, and residual DNA content of the cellulose tubes were evaluated. Human and murine skin fibroblasts and dermal lymphatic endothelial cells were isolated and cultured for recellularization studies. Biocompatibility, proliferative capacity, and ex-vivo endothelialization of the cellulose tubes were assessed as potential interposition grafts. Finally, the engineered cellulose tubes were assessed as interposing xenografts for lymphovenous anastomoses (LVA) in an ex-vivo swine limb model. The decellularized cellulose tubes exhibited a suitable microscopic structure, mechanical properties, and low residual DNA content. The tubes showed adequate biocompatibility, supported cell proliferation, and facilitated spontaneous ex-vivo endothelialization of lymphatic endothelial cells. In the swine limb model, LVA using the engineered cellulose tubes was successfully performed. This translational study presents the use of decellularized cellulose tubes as an adjunct for micro and supermicrosurgical reconstruction. The developed tubes demonstrated favorable structural, mechanical, and biocompatible properties, making them a potential candidate for improving long-term outcomes in lymphedema surgical treatment. The next translational step would be trialing the obtained tubes in a microsurgical in-vivo model. [ABSTRACT FROM AUTHOR]

The immune system plays an important role in fracture healing, by modulating the pro-inflammatory and anti-inflammatory responses occurring instantly upon injury. An imbalance in these responses can lead to adverse outcomes, such as non-union of fractures. Implants are used to support and stabilize complex fractures. Biodegradable metallic implants offer the potential to avoid a second surgery for implant removal, unlike non-degradable implants. However, considering our dynamic immune system it is important to conduct in-depth studies on the immune response to these implants in living systems. In this study, we investigated the immune response to Mg and Mg-10Gd in vivo in a rat femur fracture model with external fixation. In vivo imaging using liposomal formulations was used to monitor the fluorescence-related inflammation over time. We combine ex vivo methods with our in vivo study to evaluate and understand the systemic and local effects of the implants on the immune response. We observed no significant local or systemic effects in the Mg-10Gd implanted group compared to the SHAM and Mg implanted groups over time. Our findings suggest that Mg-10Gd is a more compatible implant material than Mg, with no adverse effects observed in the early phase of fracture healing during our 4-week study. Degradable metallic implants in form of Mg and Mg-10Gd intramedullary pins were assessed in a rat femur fracture model, alongside a non-implanted SHAM group with special respect to the potential to induce an inflammatory response. This pre-clinical study combines innovative non-invasive in vivo imaging techniques associated with multimodal, ex vivo cellular and molecular analytics. The study contributes to the development and evaluation of degradable biometals and their clinical application potential. The study results indicate that Mg-10Gd did not exhibit any significant harmful effects compared to the SHAM and Mg groups. [Display omitted] [ABSTRACT FROM AUTHOR]

Von Willebrand disease (VWD) is the most common congenital bleeding disorder. This autosomal dominant condition arises from quantitative or qualitative defects of Von Willebrand factor. To our knowledge, this study leveraged a national database to characterize the largest VWD cohort of total hip arthroplasty (THA) patients to date, assessing 90-day postoperative adverse events and 5-year revision-free survival. Adult patients who underwent primary THA for osteoarthritis were identified from January 2010 to October 2021 in a nationwide database. Patients who had and did not have VWD were matched (4:1) on age, sex, and Elixhauser Comorbidity Index and compared with multivariable logistic regression. Patients were then categorized based upon venous thromboembolism (VTE) chemoprophylaxis prescription patterns to compare bleeding and thrombotic adverse events. Of 544,851 THA patients, VWD was identified in 309 patients (0.06%). The matched cohorts contained 1,221 patients who did not have VWD and 306 patients who have VWD. On multivariable analysis, VWD patients had increased odds of 90-day VTE (odds ratio [OR] = 1.86) and hematoma (OR = 3.40) (P <.05 for all). No difference in 5-year revision-free survival was found. The VWD patients receiving aspirin or no prescriptions had greater odds of VTE (OR = 2.39, P =.048). Those on other chemoprophylaxis agents had greater odds of hematoma (OR = 4.84, P =.006). Patients with VWD undergoing THA had increased odds of 90-day VTE if using aspirin or no prescriptions, or hematoma if using other chemoprophylaxis. There is a delicate balancing act of clotting versus bleeding that must be considered in managing such patients, but it was reassuring that no difference in overall 5-year revision-free survival was found. [ABSTRACT FROM AUTHOR]

Cauda equina syndrome (CES) is a surgical emergency that often leads to debilitating chronic neuropathic pain, lower limb paralysis, loss of both faecal and urinary continence, and loss of sexual function; all of which cause a large degree of morbidity often causing psychological issues in the patient and a strain on family and their personal relationships. It is usually caused by a space occupying lesion in the lumbrosacral spinal canal causing a compressive mass effect on the peripheral nerve fibres of the cauda equina. This causes a syndrome of lower back pain, sciatica type symptoms, sensory and motor power loss of the lower limbs and perineum including loss of bladder or bowel control. Fortunately, it is relatively uncommon – affecting 1–3 per 100,000 people in England. Suspected CES as a presentation is vastly more common with about 8000 cases a year in England. It is a time-sensitive condition and as such early diagnosis and management of CES is a priority to prevent disability. When CES is diagnosed, it requires an emergency operation to decompress the cauda and prevent long-term disability. [ABSTRACT FROM AUTHOR]

Neonatal anaemia is a prevalent challenge in neonatal intensive care units. This arises from an interplay of physiological and non-physiological processes. Blood loss, diminished red blood cell production and increased erythrocyte breakdown are the primary contributors. Effective preventive and treatment strategies require an understanding of the likely underlying cause. Management of anaemia in premature infants involves additional complexities. This article provides an overview of the more important aspects of neonatal anaemia. It considers the various contributing factors and pathophysiology in term and preterm infants. We suggest an approach to the diagnosis and management of neonatal anaemia, highlighting the value of the various diagnostic tests within the neonatal intensive care unit. Crucial aspects addressed include the preventive measures that clinicians need to focus on and evidence-based treatment strategies. [ABSTRACT FROM AUTHOR]

The effective management of older patients with fragility fractures of the femur remains central to modern trauma care. Processes of assessment and communication alongside means of identifying poor performance are vital to improving care in this population. The National Hip Fracture Database (NHFD) now contains around 1 million cases and has evolved over time to reflect contemporary practices in the care of older injured patients. The NHFD is in a unique position to inform hip fracture care and the wider global management of injured older patients. This report provides an update and details the processes within the NHFD, the scope, lessons learned and highlights future direction. [ABSTRACT FROM AUTHOR]

This paper presents a new analytical model for prediction of cutting forces in binary materials such as metal matrix composites (MMC) based on the cutting power. The model considers the effect of matrix shearing, reinforcement particles fracture and debonding as well as frictional contact between the tool and the particles to predict cutting forces required to form free surfaces. Linear orthogonal cutting on Al2124-SiC MMC with different cutting speed and depth of cuts were performed. The developed model shows a better performance compared with other available models in the literature to predict cutting forces while the experimental results reveal shearing and fracture as the main chip formation mechanism. [ABSTRACT FROM AUTHOR]

[Display omitted] High failure rates present challenges for surgical and interventional therapies for peripheral artery disease of the femoropopliteal artery (FPA). The FPA's demanding biomechanical environment necessitates complex interactions with repair devices and materials. While a comprehensive understanding of the FPA's mechanical characteristics could improve medical treatments, the viscoelastic properties of these muscular arteries remain poorly understood, and the constitutive model describing their time-dependent behavior is absent. We introduce a new viscoelastic constitutive model for the human FPA grounded in its microstructural composition. The model is capable of detailing the contributions of each intramural component to the overall viscoelastic response. Our model was developed utilizing fractional viscoelasticity and tested using biaxial experimental data with hysteresis and relaxation collected from 10 healthy human subjects aged 57 to 65 and further optimized for high throughput and automation. The model accurately described the experimental data, capturing significant nonlinearity and hysteresis that were particularly pronounced circumferentially, and tracked the contribution of passive smooth muscle cells to viscoelasticity that was twice that of the collagen fibers. The high-throughput parameter estimation procedure we developed included a specialized objective function and modifications to enhance convergence for the common exponential-type fiber laws, facilitating computational implementation. Our new model delineates the time-dependent behavior of human FPAs, which will improve the fidelity of computational simulations investigating device-artery interactions and contribute to their greater physical accuracy. Moreover, it serves as a useful tool to investigate the contribution of arterial constituents to overall tissue viscoelasticity, thereby expanding our knowledge of arterial mechanophysiology. The demanding biomechanical environment of the femoropopliteal artery (FPA) necessitates complex interactions with repair devices and materials, but the viscoelastic properties of these muscular arteries remain poorly understood with the constitutive model describing their time-dependent behavior being absent. We hereby introduce the first viscoelastic constitutive model for the human FPA grounded in its microstructures. This model was tested using biaxial mechanical data collected from 10 healthy human subjects between the ages of 57 to 65. It can detail the contributions of each intramural component to the overall viscoelastic response, showing that the contribution of passive smooth muscle cells to viscoelasticity is twice that of collagen fibers. The usefulness of this model as tool to better understand arterial mechanophysiology was demonstrated. [ABSTRACT FROM AUTHOR]

The growth of the sphenoethmoidal and sphenofrontal suture in the anterior cranial base (ACB) terminates around 7 years old; therefore, ACB is used as a reference structure for superimposing radiographs in 2-dimensions (2D) and 3-dimensions (3D). The data in the literature regarding the cessation of growth of ACB in 3D is insufficient. The study aimed to evaluate the volumetric changes of ACB in growing patients on cone-beam computed tomography (CBCT) data in 3D. The CBCT sample was obtained from a repository of scans of subjects (n = 30) aged 6-11 years with no craniofacial anomalies or growth-related disorders. CBCTs were taken at 2 time points (approximately 12 months apart). The mean age at the initial scan (T1) was 8.4 ± 0.89 years, and the follow-up scan (T2) was 9.6 ± 0.99 years. The bones of the ACB were segmented, and 3D models of the bones were generated using Mimics software. The volumetric measurement was performed on the 3D-rendered model. Linear measurements were performed on the slices. The volumetric analysis of the ACB between T1 and T2 showed a significant change (P <0.0001). There were no significant differences in volumetric changes of the ACB between the male and female subjects. The linear measurements on the right side of the cranial base showed continued growth between T1 and T2. In the studied sample, growth-related changes of ACB were observed through volumetric analysis after 7 years old. • Changes in the anterior cranial base (ACB) continue after 6 years old. • Measurements on the right side of the ACB show more growth than on the left side. • The volume of the region that includes the ACB increases. [ABSTRACT FROM AUTHOR]

The planning and coordination of an orthopaedic trauma list is a core skill. It is applicable to all grades of trainee and senior staff, as to be successful, it requires input and coordination by all members of the clinical team. There are several, predictable domains of patient care that must be considered and balanced when constructing a trauma list. These are broad and are only in part clinical, as logistical and philosophical elements also play a role. We outline the issues impacting on trauma list construction and coordination and provide a framework to base decision making on. [ABSTRACT FROM AUTHOR]

• Lay people living in different countries have varying profile preferences. • Sex and racial identity influence profile preferences. • Upturned nose is less desired in all the assessed locations. This study aimed to assess the facial profile preferences of lay people in seven locations from different countries and whether their place of residence, sex, age, race, education, or income influenced the decision. After altering the lip and nose in 1 mm increments in the sagittal and sagittal/vertical directions, 50 profile silhouettes with white-like facial features were rated by evaluators. The soft tissue values were integrated into the profiles, and profile preferences were identified for each location. An ANOVA with post hoc Tukey test was used to compare the differences in mean preference in each location. A multivariable regression model was used to assess the effect of the demographics of the evaluator on preference. Thirteen profiles were ultimately analyzed. The mean for profile preference was significantly different across locations (P < 0.0001). For evaluators in the United States and Lebanon, the most preferred profile had the original lip and original nose. In Switzerland and South Africa, retrusive lips, and a small and less upturned nose was most preferred. In Japan and Saudi Arabia, the most preferred profile had the original lip and a protrusive nose that was less upturned. A protrusive lip with a small, upturned nose was preferred in Turkey. Profile change (P < 0.0001), location (P < 0.0001), sex (P < 0.0001), and race (P = 0.02) were significant confounders; in contrast, age, education, and income were not significant. Profile preference is different among the seven locations. For the most part, lay people prefer profiles within one SD from white norms. Also, an upturned nose is the least favored in most of the locations. Sex and race are also significant confounders. An orthodontic treatment plan decision is affected by an individual's preference for their facial appearance. This study helps clinicians understand how racial and regional differences may affect patients' preferences and, therefore, their expectations for orthodontic treatment results. [ABSTRACT FROM AUTHOR]

Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE. Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199. [ABSTRACT FROM AUTHOR]

• The straight-wire appliance is an individualized, fully-programmed appliance system. • The Six Keys to Normal (Optimal) Occlusion laid the foundation for straight-wire appliance. • Recent advances include the customization of orthodontic bracket systems using computer-aided design/computer-aided manufacturing and three-dimensional printing technologies. • Parameters of an optimal arch are defined by individual tooth positions and collective tooth positions. • A bracket set is assigned to an arch based on its interim core discrepancy. The straight-wire appliance is an individualized, fully-programmed appliance system that has been in clinical use since the early 1970s. A study of tooth positions in individuals with naturally occurring harmonious occlusions led to the discovery of the Six Keys to Normal (Optimal) Occlusion which provided data for bracket features and prescription values incorporated into the straight-wire appliance. It was based on the notion that tooth anatomy, morphology, and optimal positions were alike enough among individuals, regardless of age, sex, or race to justify using prefabricated brackets with average prescription values. New technologies have led to advancements in appliance customization. Customized brackets can be made-to-order with one-of-a-kind prescription values and bracket base contours that fit precisely to the morphologic characteristics of the teeth. If costs and material qualities were comparable, would treatment efficiency or treatment outcomes be superior when using a customized appliance compared with a prefabricated straight-wire appliance? If not, why not? [ABSTRACT FROM AUTHOR]

• This study characterized natural forearm and wrist behavior during daily activities • Subjects spent 50% of time in the central 20% of their functional range of motion • Most movements were slow, and movement speed dropped off exponentially • Subjects often merged dart-thrower's motion with twist from pronation to supination • Importance of dart-thrower's motion may derive from the hand-to-mouth movement During activities of daily living, the main degrees of freedom of the forearm and wrist—forearm pronation-supination (PS), wrist flexion-extension (FE), and wrist radial-ulnar deviation (RUD)—combine seamlessly to allow the hand to engage with and manipulate objects in our environment. Yet the combined behavior of these three degrees of freedom is relatively unknown. To provide a characterization of natural forearm and wrist kinematics (joint configuration, movement direction, and speed) during activities of daily living. This is a descriptive cross-sectional study. Ten healthy subjects performed 24 activities of daily living chosen to represent a wide variety of activities, while we measured their PS, FE, and RUD angles using electromagnetic motion capture. The orientation of the forearm and wrist was represented in the three-dimensional "configuration space" spanned by PS, FE, and RUD. From the time course of forearm and wrist orientation in configuration space, we extracted three-dimensional distributions of joint configuration, movement direction, and speed. Most joint configurations were focused in a relatively small area: subjects spent roughly 50% of the time in the central 20% of their functional range of motion. Some movement directions were significantly more common than others (p < 0.001); in particular, the direction of the dart-thrower's motion (DTM) was about three times more common than motion perpendicular to it. Most movements were slow: the likelihood of moving at increasing speeds dropped off exponentially. Interestingly, the most common high-speed motion combined the DTM with a twist from pronation to supination. As this motion allows one to pick up an object in front of one's body and bring it to the head, it is essential for self-care. Thus, although many activities of daily living follow the DTM without significant forearm rotation, the greatest importance of the DTM may lie in its combination with forearm rotation. Despite the wide variety of activities, we found evidence of preferred movement behavior, and this behavior showed significant coupling between the wrist and forearm. [ABSTRACT FROM AUTHOR]

Though a circulation-airway-breathing (CAB) resuscitation sequence is now widely accepted in administering CPR over the airway-breathing-circulation (ABC) sequence following cardiac arrest, current evidence and guidelines vary considerably for complex polytraumas, with some prioritizing management of the airway and others advocating for initial treatment of hemorrhage. This review aims to evaluate existing literature comparing ABC and CAB resuscitation sequences in adult trauma patients in-hospital to direct future research and guide evidence-based recommendations for management. A literature search was conducted on PubMed, Embase, and Google Scholar until September 29, 2022. Articles were assessed for comparison between CAB and ABC resuscitation sequences, adult trauma patients, in-hospital treatment, patient volume status, and clinical outcomes. Four studies met the inclusion criteria. Two studies compared the CAB and ABC sequences specifically in hypotensive trauma patients, one study evaluated the sequences in trauma patients with hypovolemic shock, and one study in patients with all types of shock. Hypotensive trauma patients who underwent rapid sequence intubation before blood transfusion had a significantly higher mortality rate than those who had blood transfusion initiated first (50 vs 78% P < 0.05) and a significant drop in blood pressure. Patients who subsequently experienced post-intubation hypotension (PIH) had increased mortality over those without PIH. overall mortality was higher in patients that developed PIH (mortality, n (%): PIH = 250/753 (33.2%) vs 253/1291 (19.6%), p < 0.001). This study found that hypotensive trauma patients, especially those with active hemorrhage, may benefit more from a CAB approach to resuscitation, as early intubation may increase mortality secondary to PIH. However, patients with critical hypoxia or airway injury may still benefit more from the ABC sequence and prioritization of the airway. Future prospective studies are needed to understand the benefits of CAB with trauma patients and identify which patient subgroups are most affected by prioritizing circulation before airway management. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the MYBPC3 gene are the leading genetic cause of hypertrophic cardiomyopathy (HCM) resulting in reduced functional myosin-binding protein C (MyBP-C) levels. Studies have shown that adult patients with pathogenic sarcomere variant-HCM exhibit higher incidence of major clinical events than genotype-negative HCM patients. With the emergence of gene replacement therapies, characterizing the natural history of MYBPC3 + HCM is essential to inform future development of this class of targeted therapies. We conducted an analysis of all adult MYBPC3 + HCM patients enrolled in SHaRe (Sarcomeric Human Cardiomyopathy Registry) based on their primary diagnosis at the age of 18-39, 40-59, and ≥60 years. As of September 2023, 1493 adult HCM patients with a pathogenic or likely pathogenic variant in MYBPC3 had enrolled in SHaRe, a multicenter registry involving 12 cardiac centers in the US, EU, and Australia. This analysis included 635 patients (42.5%) diagnosed at 18–39 years, 659 (44.1%) at 40–59 years, and 199 (13.3%) at ≥60 years. Duration of follow-up in the three cohorts was 8.4, 6.6, and 4.5 years, respectively. Demographics, genotype, first echocardiographic metrics, and time to major clinical events were compared across the three groups. Most patients diagnosed at 18–39 and 40–59 years were males (67.0% and 56.3% respectively), while those diagnosed at ≥60 years were primarily female (59.5%). Family history of HCM and proband status were comparable across cohorts (range of 56.3 – 65.7% and 88.0 – 91.5%, respectively). Patients in the youngest cohort presented with the greatest left ventricular maximal wall thickness (median of 19 mm, 18 mm, and 17 mm for the 18 – 39, 40 – 59, and ≥60 years cohorts, respectively). Symptom burden was comparable across cohorts, as the proportion of patients with NYHA III/IV was 13.1%, 10.5%, and 11.4%, respectively. The prevalence of patients having SRT, syncope and need for transplant or left ventricular assist device (LVAD) were highest in the youngest cohort (see Table). Across all three cohorts, patients experienced atrial fibrillation (AF) at 13.7%, the ventricular arrhythmia (VA) composite at 5.3%, and the heart failure (HF) composite at 9.1%. Adult MYBPC3 + HCM patients of all ages are at risk for serious clinical manifestations including heart failure, arrhythmias, and sudden cardiac death (SCD). These findings underscore the importance of genetic diagnosis and development of targeted therapies to restore MyBP-C levels, which could potentially modify the natural history of the disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Palaeogeography of Kalahari and Río de la Plata cratons and Arachania microplate. • Neoproterozoic subduction reversal. • Transition from Ediacaran subduction-related to intraplate and collisional magmatism. • Differentiation of mantle-derived basaltic melts. • Remnants of the Cape Granite occur in Uruguay. We present new zircon U-Pb geochronological and Hf-O isotope data as well as whole rock geochemical and Sr-Nd-Pb isotope geochemical data of Ediacaran magmatic rocks from the Cuchilla Dionisio (CDT), Nico Pérez (NPT) and Tandilia (TT) terranes in Uruguay. Three different rock suites are recognized in the NPT. The Group 1 rocks are high Ba-Sr granodiorite, monzonite and syenite that formed from a subduction-related mafic source between 610 ± 3 and 593 ± 5 Ma, most likely in an extensional setting. The Group 2 plutons, syenite, formed from a mafic source between 573 ± 8 and 563 ± 7 Ma and were emplaced in an intraplate setting at the extended eastern Rio de la Plata cratonic margin. The Group 3 rocks as well as the La Paz Granite in the TT are intraplate granites that formed by crustal melting and/or by the incorporation of crustal melts at c. 557 ± 4 Ma. The Early Ediacaran Valdivia Pluton in the CDT is a subduction-related granite that formed from a mafic melt at an active continental margin. The 571 ± 3 and 566 ± 6 Ma subduction-related CDT José Ignacio and Florencia granites were emplaced at or close to an active margin. They, like the Valdivia Granite provide only little evidence of incorporating crustal rocks and/or melts. The coeval Maldonado and Rocha granites in the CDT are subduction-related but were emplaced in a distal position to the arc. The Early Cambrian Santa Teresa Granite is a collision-related pluton that formed during the final assembly of SW Gondwana at 532 ± 6 Ma. It is evident that the Ediacaran to Early Cambrian igneous rocks in the southern Dom Feliciano Belt in Uruguay originated from dissimilar source regions and were emplaced in different tectonic settings at different times. The data indicate a transition from Early Ediacaran subduction-related, arc-type magmatism to intraplate and, finally to Late Ediacaran/Early Cambrian collision-related igneous activity in the Uruguayan sector of the southern Dom Feliciano Belt. [ABSTRACT FROM AUTHOR]

Treatment strategies for paratesticular rhabdomyosarcoma (PT RMS) are based on stage, which requires accurate lymph node (LN) evaluation. Previous methodology for determining quantity of LN for negative nodal status is based on LN positivity rates, without accounting for the relationship between LNs or amongst patients. This study aims to quantify the chance of missing involved LNs based on LN yield (LNY) using a previously established methodology in comparison to current recommendations. Using the National Cancer Database, patients with a diagnosis of PT RMS were queried from 2004 to 2018. Patients >10 years and those ≤10 years with cN1 disease were included, based on COG guidelines for who should undergo retroperitoneal LN sampling (RPLNS). The beta-binomial model was used to calculate the rate of false negative RPLNS and identified the LNY threshold to reduce the risk of a missing an involved LN node to <10 %. Sixty-two patients were included for analysis over the study period. Median LNY was 17 (IQR 9–28.75), and the median number of involved LNs was 2.5 (IQR 2–5). The median LN density was 0.27 (IQR 0.10–0.34). Application of the beta-binomial model identified that a LNY of 26 LNs corresponds to a <10 % chance of missing occult disease (Fig. 3). Previous models estimate that sampling of 7–12 LN is adequate for accurate staging. However, the beta binomial model quantifies sampling at least 26 LNs to reduce the chance of missing occult metastatic disease to <10 % in the majority of patients. Surgeons should consider this false negative rate during RPLNS for patients with PT RMS. III. • LN sampling is important in PT RMS for staging purposes. • Based on the beta-binomial model, 26 LNs need to be removed for a <10 % chance of missing occult metastatic disease. • Surgeons should consider this when performing RPLND for men and boys with PT RMS. [ABSTRACT FROM AUTHOR]

Tenaya Therapeutics is developing TN-201, the first AAV9-mediated gene therapy for the leading cause of genetic HCM, MYBPC3 -associated hypertrophic cardiomyopathy (MYBPC3 + HCM). Patients with high levels of preexisting neutralizing antibodies (NAbs) to AAVs may fail to achieve desired transgene expression and/or be at risk of an inflammatory response. There have been no studies assessing AAV9 seroprevalence in MYBPC3 + HCM patients. Tenaya initiated the first observational seroprevalence study of MYBPC3+ HCM patients at US HCM clinics, enrolling participants 18-65 years of age with HCM and with one or more MYBPC3 mutation. Demographics, medical histories, symptom burden, and a single blood draw were collected. NAb titers were assessed via assay. Participants with preexisting NAb titers <1:40 were classified as seronegative to AAV9. Total antibody (TAb) titer to AAV9 was also assessed to compare with NAb titers. By March 2024, 104 participants had enrolled in this study. Median age was 48 years (IQR: 35-56 years) and 65% were male. The majority of participants (57%) had nonobstructive HCM, which included patients post-myectomy. Available data indicate that 78% (69/88) of participants with MYBPC3 + HCM were AAV9 seronegative. Preexisting AAV9 TAb titer strongly correlated with AAV9 NAb. AAV9 serostatus did not vary by gender, age, race, geography, clinical state, or medical history. Results suggest that MYBPC3 + HCM patients in the US have low levels of pre-existing AAV9 NAbs and that most would meet current NAb eligibility for clinical studies of TN-201 gene therapy. Tenaya is enrolling patients in MyPEAK-1, a Phase 1b/2a trial evaluating the safety, tolerability, and exploratory efficacy measures of TN-201 in MYBPC3 + HCM. [ABSTRACT FROM AUTHOR]

Esophageal cancers that invade the submucosa (T1b) have increased risk for occult lymph node metastases. To avoid the morbidity and recovery from esophagectomy, patients with cT1bN0 tumors have been increasingly managed endoscopically. We hypothesized that tumor attributes could predict upstaging and outcome associated with surgical and endoscopic treatment. Our objective was to evaluate the comparative effectiveness of esophagectomy across different cT1bN0 tumor attributes. Treatment-naïve patients who underwent endoscopic management or esophagectomy for a clinical stage cT1bN0 esophageal cancer diagnosed between 2010 and 2018 in the National Cancer Database were identified. Factors associated with upstaging were assessed by logistic regression. Adjusted survival was assessed by Kaplan-Meier analysis of 528 propensity-matched pairs and accelerated time failure models, stratified across tumor attributes. Overall, 1469 patients classified as cT1bN0 were identified; 926 underwent esophagectomy and 543 were managed endoscopically. In general, patients who were managed endoscopically were older (median, 71; interquartile range, 63-78; vs 66; interquartile range, 60-72; P <.0001) with smaller tumors compared with the patients who were managed with esophagectomy. Nodal upstaging was associated with lymphovascular invasion (odds ratio [OR], 6.88; confidence interval [CI], 4.39-10.77; P <.0001), poor tumor differentiation (OR, 2.77; CI, 1.30-5.88; P =.0081), and tumor size >1 cm (OR, 3.19; CI, 1.49-6.83, P =.0028). Overall survival was better among propensity-matched patients who underwent esophagectomy (5-year 68.4% vs 59.7% endoscopic, P <.001). However, accelerated time failure models suggested similar outcomes among patients with well-differentiated tumors managed surgically or endoscopically. Esophagectomy was associated with improved survival for cT1bN0 esophageal cancer; however, endoscopic treatment may achieve similar survival in patients with favorable tumor attributes. Further study is warranted. A, Propensity-matched Kaplan-Meier curve comparing 5-year survival in patients who received esophagectomy versus endoscopic treatment for cT1bN0 esophageal cancer. B, Kaplan-Meier curve comparing 5-year survival in patients with well-differentiated tumors that received esophagectomy versus endoscopic treatment for cT1bN0 esophageal cancer. Blue line shows endoscopic intervention and red line shows esophagectomy. OR , Odds ratio; CI , confidence interval; HR , hazard ratio. [Display omitted] [ABSTRACT FROM AUTHOR]

Dynamic yet accurate species lists for protected areas are essential for conservation and biodiversity research. Even when such lists exist, changing taxonomy, ongoing species migrations and invasions, and new discoveries of historically overlooked species mean static lists can become rapidly outdated. Biodiversity databases such as the Global Biodiversity Information Facility, and citizen science platforms such as iNaturalist, offer rapidly accessible, georeferenced data, but their accuracy is rarely tested. Here we compare species lists generated for two of the world's oldest, more famous protected areas – Yosemite National Park in California, United States and Royal National Park in New South Wales, Australia – using both automated data extraction techniques and extensive manual curation steps. We show that automated list creation without manual curation offers inflated measures of species diversity. Lists generated from herbarium vouchers required more curation than lists generated from iNaturalist, with both incorrect coordinates attached to vouchers and long-outdated names inflating voucher-based species lists. In comparison, iNaturalist data had relatively few errors, in part due to continual curation by a large community, including many botanical experts, and the frequent and automatic implementation of taxonomic updates. As such, iNaturalist will become an increasingly accurate supplementary source for automated biodiversity lists over time, but currently offers poor coverage of graminoid species and introduced species relative to showier, native taxa, and relies on continued expert contributions to identifications. At this point, researchers must manually curate lists extracted from herbarium vouchers or static park lists, and integrate these data with records from iNaturalist, to produce the most robust and taxonomically up-to-date species lists for protected areas. • Accurate species lists are crucial for conservation and research in protected areas. • Most lists based on herbarium vouchers but iNaturalist data is valuable supplement. • Integrating multiple data streams provides most robust species lists. • Lists need curation and updating to account for errors and taxonomic changes. • Data flow issues are biggest barrier to data synthesis. [ABSTRACT FROM AUTHOR]

The family of nanomagnetic arrays termed artificial spin ice (ASI) possess a vast range of metastable microstates. These states exhibit both exotic fundamental physics and more recently applied functionality, garnering attention as reconfigurable magnonic circuits and neuromorphic computing platforms. However, open questions remain on the role of microstate imperfections or angular disorder – particularly in the GHz response of the system. We report a study on the GHz dynamics of a series of five carefully prepared microstates in the same ASI sample, with both coexistence of vortex and uniformly magnetized macrospins, and disorder in the orientation of the macrospins at different vertices. We observe microstate-specific mode frequency shifting, mode creation and mode crossing. This versatility of characteristic spin-wave (SW) peaks for specific magnetic microstates in ASI enables identification of microstate configurations via SW spectral characterization. The wide reconfigurability of microstate-specific SW dynamics also opens avenues for developing rich magnonic devices operating in the GHz frequency regime and advances the understanding of ASI physics. [Display omitted] • Experimental and numerical study of reconfigurable magnonics in nanoscale artificial spin ice. • External field controlled magnetic microstate origami leads to rich magnon spectra. • BLS spectral fingerprinting of magnetic microstates leads to advancement of ASI physics. • Potential for on-chip data communication and processing using magnons in ASI systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • We report a global systematic review of wetland Cultural Ecosystem Services (CES), synthesizing 861 papers. • We found published evidence of CES provided by wetlands in 175 countries and territories. • Recreation/tourism was the most frequently reported CES, with 63 different leisure activities identified. • Probabilities that a paper was open access and had ≥ 1 in-country author varied among continents and years. • Synthesis of published economic values yield a mean of £57262 ha−1 yr−1 for the cultural benefits of wetlands. Wetlands make a disproportionately large contribution to global biodiversity and provide critical ecosystem services for humanity. Yet, our understanding of the cultural ecosystem services (CES) provided by wetlands remains limited, with benefits often only recognised at local scales. To address this knowledge gap, we conducted a global systematic review of wetland CES. Our synthesis addressed key questions related to the provision of CES by different types of wetlands, their economic value, their co-occurrence and associations with other ecosystem services, threats to the provision of CES by wetlands, as well as the availability and use of CES information. Based on 861 published papers (1968–2022) in 17 languages, we found evidence of CES provided by wetlands in 175 countries and territories, highlighting that wetlands are globally important for the provision of CES. Recreation/tourism was the most frequently reported CES (40 %), with cultural identity/heritage (16 %) and education/learning/knowledge (13 %) also well-represented. In contrast, examples of sense of place (4 %) and bequest (4 %) were least frequent. Our synthesis of published estimates yielded a mean of £57262 ha−1 yr−1 for the cultural benefits of wetlands; however, this mean should be interpreted with caution given that we documented a very wide range of estimates for each CES type of <£1–£1065205 ha−1 yr−1. Threats to wetland CES were documented in 45 % of papers, and included wetland destruction, pollution, and climate change. The probability that a CES paper would be available open access, and the probability that a published paper featured at least one author affiliated with the country where the study was conducted, both varied significantly among continents and publication years. Conservation outcomes related to CES featured in 13 % of papers, whilst 10 % made policy/management recommendations. Our study highlights the links between wetlands and human culture, emphasising their importance in motivating future wetland creation and restoration. [ABSTRACT FROM AUTHOR]

Large vessel occlusion-acute ischemic stroke (LVO-AIS) is infrequent in young adults and exhibits distinct stroke mechanisms compared to older adults. This study sought to evaluate the impact of varying stroke etiologies on treatment-related outcomes in young adults with LVO-AIS, an aspect that remains unclear. This retrospective cohort study included patients aged 18-50 presenting with AIS from January 2017 to December 2021 within our multi-center stroke network. Patients with LVO on CTA/MRA at presentation were included. We assessed demographics, stroke etiology (TOAST classification), and treatment-related outcomes. Based on intervention received, patients were divided into 5 groups [IV-thrombolysis (IVT) only, Mechanical Thrombectomy (MT) only, IVT+MT, no treatment, unsuccessful MT]. Among 1210 AIS patients, 220 with LVO were included. The median age was 42 (36, 46). 75 (34.1 %) patients underwent successful MT (46.7 % received IVT+MT). 26 (11.8 %) received IVT only, 110 (50 %) received neither intervention, and 9 (4.1 %) underwent unsuccessful MT. Per TOAST, 17.4 % had large artery atherosclerosis (LAA), 19.2 % cardio-embolism, 28.6 % stroke of other etiology, and 34.7 % had undetermined etiology. Favorable thrombectomy outcomes (TICI 2b/2c/3) were observed in 87.2 %. Discharge NIH Stroke Scale (NIHSS) scores improved for patients with IVT+MT in all TOAST categories except LAA. Young adults with LVO-AIS had good outcomes irrespective of stroke etiology, except LAA, which was associated with a higher discharge NIHSS. Moreover, 50 % of young adults in our study received no intervention, a quarter of those owing to delayed presentation. Further studies are needed to identify barriers in seeking acute treatment in young adults with LVO-AIS. [ABSTRACT FROM AUTHOR]

[Display omitted] • US residents only showed a relatively small difference in plasma/serum Se. • Se concentration in alfalfa leaves in US states modelled environmental Se exposure. • States with low alfalfa Se had a higher death rate from COVID-19 than other states. • Atmospheric dimethyldiselenide may reflect Se concentration in alfalfa leaves. • Lung exposure to dimethyldiselenide which activates Nrf2 may explain our results. Environmental selenium (Se) distribution in the US is uneven, yet US residents appear to have a relatively narrow range of serum Se concentrations, according to the NHANES III survey data; this is probably due to the modern food-distribution system. In the US, Se concentration in alfalfa leaves has been used as a proxy for regional Se exposure (low, medium or high, corresponding to ≤ 0.05, 0.06–0.10 and ≥ 0.11 ppm respectively). Se in plants, soil, water, and bacteria can be transformed into volatile dimethyldiselenide, which can be inhaled and excreted via the lung. Hence, pulmonary Se exposure may be different in states with different atmospheric Se levels. We found a significantly higher death rate from COVID-19 in low-Se states than in medium-Se or high-Se states, though the case densities of these states were not significantly different. Because inhaled dimethyldiselenide is a potent inducer of nuclear-factor erythroid 2 p45-related factor 2 (Nrf2), exposure to higher atmospheric dimethyldiselenide may increase Nrf2-dependent antioxidant defences, reducing the activation of NFκB by SARS-CoV-2 in the lung, thereby decreasing cytokine activation and COVID-19 severity. Atmospheric dimethyldiselenide may thereby play a role in COVID-19 mortality, although the extent of its involvement is unclear. [ABSTRACT FROM AUTHOR]

Introduction: The iodinated contrast material (ICM) shortage of 2022 has affected healthcare systems worldwide, forcing institutions to adapt by implementing interventions to conserve ICM without compromising patient care. We aim to present the practices proven to be effective in reducing ICM consumption to improve resource allocation in trauma patients.Methods: A literature search of PubMed, Google Scholar, and Cochrane was conducted. Studies investigating the utility of ICM in the management of trauma & emergency surgery patients, as well as institutional interventions that were implicated as a response to the ICM shortage of 2022 were included for review.Results: Eight articles were selected and reviewed. The use of alternative, non-contrast-enhanced imaging modalities, particularly non-contrast-enhanced CT (NECT), was found to be effective in reducing ICM consumption. Other institutions have implemented strategies to reduce the ICM dose for each imaging study performed, including decreasing ICM dose itself as well as reducing tube voltage, which was shown to reduce ICM use by 50%. Waste minimization by splitting single-dose contrast vials into smaller aliquots utilized for multiple imaging studies has also been an effective method. Additionally, assembling a Radiology Command Center Team, responsible for monitoring ICM supplies while offering 24/7 consults regarding options for alternative imaging, has resulted in an overall reduction in contrast consumption of 50% in 7 days.Conclusion: In response to the ICM shortage of 2022, most healthcare institutions have found the use of alternative imaging modalities to be effective in reducing ICM consumption. Other effective measures include ICM dose reduction and ICM waste minimization. [ABSTRACT FROM AUTHOR]

Glenoid reconstruction is indicated for recurrent glenohumeral instability with significant glenoid bone deficiency. Coracoid autograft (Latarjet) and distal tibial osteochondral allograft (DTA) reconstructions have been used to successfully restore glenohumeral stability. Relative advantages and disadvantages associated with each reconstruction technique have been described. However, direct comparisons of functional glenohumeral biomechanics associated with Latarjet vs. DTA reconstruction are lacking. This study was designed to compare these 2 glenoid reconstruction techniques with respect to joint kinematics and cartilage pressure mapping using a robotic testing system. In accordance with institutional review board policies, human cadaveric shoulders (n = 8) were cyclically tested in the neutral position and 90° of external rotation with 60° and 90° of abduction under a 45-N joint-compression load to measure clinically relevant translations, loads, and torques. Joint contact pressure maps were obtained under a 120-N joint-compression load using pressure mapping sensors. After confirming that a 25% anterior glenoid defect resulted in glenohumeral dislocation, testing was performed to compare 3 conditions: native intact glenoid, 25% anterior glenoid defect with Latarjet reconstruction, and 25% anterior glenoid defect with DTA reconstruction. Analyses of variance and t tests were used to analyze data with statistical significance set at P <.05. Significant differences in anterior translation, inferior drawer, anterior drawer, compression loads, horizontal abduction, negative elevation (adduction), and external rotation torques during cyclical testing in 90° of external rotation with 60° and/or 90° of abduction were noted when comparing the 2 different glenoid bone reconstruction techniques to native, intact shoulders. The only significant difference between Latarjet and DTA reconstructions for measured translations, loads, and torques was a significantly higher absolute maximum compressive load for Latarjet compared to DTA at 60° of abduction. Latarjet coracoid osseous autograft and distal tibial osteochondral allograft reconstructions of large (25%) glenoid bone defects prevent failure (dislocation) and are associated with significant glenohumeral kinematic differences that largely confer less translation, load, and torque on the joint in abduction when compared to the native state. These findings suggest that these 2 surgical techniques exhibit similar glenohumeral kinematics such that each provides adequate functional stability following anterior glenoid bone reconstruction. Joint compression load and articular contact pressure distribution may favor distal tibial osteochondral allograft reconstruction for treatment of large (25%) anterior glenoid bone defects associated with shoulder instability. [ABSTRACT FROM AUTHOR]

The direct coupling of solid-phase microextraction (SPME) to mass spectrometry (MS) (SPME-MS) has proven to be an effective method for the fast screening and quantitative analysis of compounds in complex matrices such as blood and plasma. In recent years, our lab has developed three novel SPME-MS techniques: SPME-microfluidic open interface-MS (SPME-MOI-MS), coated blade spray-MS (CBS-MS), and SPME-probe electrospray ionization-MS (SPME-PESI-MS). The fast and high-throughput nature of these SPME-MS technologies makes them attractive options for point-of-care analysis and anti-doping testing. However, all these three techniques utilize different SPME geometries and were tested with different MS instruments. Lack of comparative data makes it difficult to determine which of these methodologies is the best option for any given application. This work fills this gap by making a comprehensive comparison of these three technologies with different SPME devices including SPME fibers, CBS blades, and SPME-PESI probes and SPME-liquid chromatography-MS (SPME-LC-MS) for the analysis of drugs of abuse using the same MS instrument. Furthermore, for the first time, we developed different desorption chambers for MOI-MS for coupling with SPME fibers, CBS blades, and SPME-PESI probes, thus illustrating the universality of this approach. In total, eight analytical methods were developed, with the experimental data showing that all the SPME-based methods provided good analytical performance with R 2 of linearities larger than 0.9925, accuracies between 81% and 118%, and good precision with an RSD% ≤ 13%. [Display omitted] • Rapid screening and quantitative analysis were achieved by SPME-MS direct coupling. • SPME with different geometries including fiber, blade and probe were studied. • Three SPME-MS techniques including MOI-MS, CBS-MS and PESI-MS has been investigated. • High throughput SPME were achieved by automated 96 Concept system. • The methods showed good analytical performance for drugs of abuse analysis. [ABSTRACT FROM AUTHOR]

Submucous cleft palate (SMCP) is an uncommon subtype of cleft palate that is associated with symptoms of velopharyngeal insufficiency (VPI), the most common being hypernasal speech. A high proportion of patients also suffer from conductive hearing loss, which is thought to be due to eustachian tube dysfunction. A number of surgical techniques have been proposed to correct the anatomical defect that is responsible for VPI. This exploratory study aims to describe surgical techniques and clinical outcomes in a series of patients who underwent surgical repair of SMCP at a single regional specialist cleft centre between 1999 and 2018. Through a retrospective case note review, records of 57 patients who underwent SMCP repair between the ages of 6 months and 16 years were examined. Patients underwent one of the three surgical techniques: Intravelar Veloplasty, Furlow or a novel technique we have termed as "Hemi-Furlow". Hypernasality, measured on the Great Ormond Street Speech Assessment, showed evidence of improvement post-operatively in all three surgical groups (P <0.005), with no evidence to favour any specific approach. Post-operative complications, including wound dehiscence and fistulae, occurred in nine patients (15.8%). Nine patients (15.8%) required revisional surgery, either due to post-operative complications or persistent speech problems. Otological disease was present in 54.4% of patients, comprising conductive hearing loss due to otitis media with effusion (52.6%) and sensorineural hearing loss (1.8%). There is now a need for large, multi-centre studies with robust outcomes measures to further examine relationships between surgical techniques and clinical outcomes in people born with SMCP. [ABSTRACT FROM AUTHOR]

Improved analytical methods for the metabolomic profiling of tissue samples are constantly needed. Currently, conventional sample preparation methods often involve tissue biopsy and/or homogenization, which disrupts the endogenous metabolome. In this study, solid-phase microextraction (SPME) fibers were used to monitor changes in endogenous compounds in homogenized and intact ovine lung tissue. Following SPME, a Biocrates AbsoluteIDQ assay was applied to make a downstream targeted metabolomics analysis and confirm the advantages of in vivo SPME metabolomics. The AbsoluteIDQ kit enabled the targeted analysis of over 100 metabolites via solid-liquid extraction and SPME. Statistical analysis revealed significant differences between conventional liquid extractions from homogenized tissue and SPME results for both homogenized and intact tissue samples. In addition, principal component analysis revealed separated clustering among all the three sample groups, indicating changes in the metabolome due to tissue homogenization and the chosen sample preparation method. Furthermore, clear differences in free metabolites were observed when extractions were performed on the intact and homogenized tissue using identical SPME procedures. Specifically, a direct comparison showed that 47 statistically distinct metabolites were detected between the homogenized and intact lung tissue samples (P < 0.05) using mixed-mode SPME fibers. These changes were probably due to the disruptive homogenization of the tissue. This study's findings highlight both the importance of sample preparation in tissue-based metabolomics studies and SPME's unique ability to perform minimally invasive extractions without tissue biopsy or homogenization while providing broad metabolite coverage. [Display omitted] • A Proof-of-concept study demonstrating SPME coupled to a Biocrates targeted metabolomics kit is presented for the first time. • SPME coupled to the Biocrates bioassay reveals drastic metabolome changes between intact and homogenized tissues. • SPME offers coverage of a great variety of analytes. • SPME is a desirable approach for delicate in vivo metabolomics studies. [ABSTRACT FROM AUTHOR]

Oncoplastic reconstruction can optimize breast conserving therapy. Nipple loss is a concern in patients with significant ptosis and breast hypertrophy particularly with pedicle undermining during tumor resection. The modified Robertson technique (No-Vertical Scar reduction) has been previously described for breast reduction in large, ptotic patients using a wide, bell-shaped inferior pedicle with only inframammary fold and peri‑areolar incisions. The purpose of this study was to evaluate the No-Vertical Scar (NVS) technique applied to oncoplastic reconstruction. Women undergoing oncoplastic breast reduction using a NVS, Wise, or Vertical method were assessed. Predictive variables included patient demographics, comorbidities, and sternal notch to nipple (SNN) distance. Outcome variables were delayed wound healing, surgical site infection, seroma, fat necrosis, nipple necrosis, use of a free nipple graft, and time between surgery and adjuvant radiation. Fifty patients met inclusion criteria using NVS (N = 15), Wise (N = 16), and Vertical (N = 19) methods. The NVS group had a significantly higher BMI (p =.009), greater sternal notch to nipple distance (p =<0.001) and increased resection volume (p =<0.001) as compared to Wise and Vertical groups. There was no significant difference in complications (p =.25). No nipple necrosis occurred, and no free nipple grafts were required. The NVS approach is a useful technique for oncoplastic reconstruction in select patients with macromastia and severe Grade II or Grade III ptosis. The wide, bell-shaped pedicle is versatile for obliterating a lumpectomy cavity and optimizing nipple perfusion if pedicle undermining occurs during resection. [ABSTRACT FROM AUTHOR]

Describe use of drowning prevention strategies among diverse adolescents. We analyzed 47,051 responses to 2012–2018 Washington statewide surveys of 8th–12th grade students, regarding formal swimming lessons, comfort in deep water (a measure of perceived water competency), and life jacket use in small watercraft. Using survey-weighted Poisson regression, we measured these strategies in relation to race/ethnicity, primary language, maternal education, and urbanicity. 78.6% of students spoke English at home. Most students reported having had formal swimming lessons (62.2%), being comfortable in deep water (65.8%), and wearing life jackets (58.5%). Students primarily speaking Spanish (11.2%) reported formal swimming lessons (PR: 0.72; 95%CI: 0.67–0.78) and perceived water competency (PR: 0.75; 95%CI: 0.70–0.80) less often than primarily English-speaking. All prevention strategies were associated with higher maternal education. Drowning prevention strategies, access to swimming lessons, life jackets, and water competency should be promoted among low-income children and those whose primary language is not English. [ABSTRACT FROM AUTHOR]