Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Author Correction: Variable water input controls evolution of the Lesser Antilles volcanic arc.

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

Variable water input controls evolution of the Lesser Antilles volcanic arc.

Oceanic lithosphere carries volatiles, notably water, into the mantle through subduction at convergent plate boundaries. This subducted water exercises control on the production of magma, earthquakes, formation of continental crust and mineral resources. Identifying different potential fluid sources (sediments, crust and mantle lithosphere) and tracing fluids from their release to the surface has proved challenging1. Atlantic subduction zones are a valuable endmember when studying this deep water cycle because hydration in Atlantic lithosphere, produced by slow spreading, is expected to be highly non-uniform2. Here, as part of a multi-disciplinary project in the Lesser Antilles volcanic arc3, we studied boron trace element and isotopic fingerprints of melt inclusions. These reveal that serpentine-that is, hydrated mantle rather than crust or sediments-is a dominant supplier of subducted water to the central arc. This serpentine is most likely to reside in a set of major fracture zones subducted beneath the central arc over approximately the past ten million years. The current dehydration of these fracture zones coincides with the current locations of the highest rates of earthquakes and prominent low shear velocities, whereas the preceding history of dehydration is consistent with the locations of higher volcanic productivity and thicker arc crust. These combined geochemical and geophysical data indicate that the structure and hydration of the subducted plate are directly connected to the evolution of the arc and its associated seismic and volcanic hazards.

Distinct clinical endpoints of Staphylococcus aureus bacteraemia complicate assessment of outcome.

BACKGROUND: We aimed to test the hypothesis that development of metastatic infection represents a distinct clinical endpoint from death due to SAB. METHODS: We conducted a retrospective observational study of adults with SAB between 20/12/2019 and 23/08/2022 (n=464). Simple logistic regression, odds ratios, and z-scores were used to compare host, clinical and microbiologic features. RESULTS: Co-occurrence of attributable mortality and metastatic infection was infrequent. Charlson Comorbidity Index and age were strongly associated with attributable mortality, but not metastatic infection. We compared patients with fatal SAB (without clinically-apparent metastatic complications, 14·4% of cohort), metastatic SAB (without attributable mortality, 22·2%), neither complication (56·7%), and overlapping fatal/metastatic SAB (6·7%). Compared to SAB without complications, fatal SAB was specifically associated with older age and multi-morbidity. Metastatic SAB was specifically associated with community acquisition, persistent fever, persistent bacteraemia, and recurrence. Endocarditis was over-represented in the fatal/metastatic SAB overlap group, which shared patient characteristics with fatal SAB. In contrast to other (predominantly musculoskeletal) metastatic complications, endocarditis was associated with increased mortality, with death occurring in older multi-morbid patients later after SAB onset. CONCLUSIONS: Patients with SAB experience distinct clinical endpoints: (i) early death, associated with multi-morbidity and age; (ii) metastatic (predominantly musculoskeletal) SAB; (iii) endocarditis, associated with late death occurring in older people with multi-morbidity, and (iv) bacteraemia without complications. These distinctions could be important for selecting appropriate outcomes in clinical trials: different interventions might be required to reduce mortality vs. improve clinical response in patients with metastatic SAB.

Clinical sub-phenotypes of Staphylococcus aureus bacteraemia.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is a clinically heterogeneous disease. The ability to identify sub-groups of patients with shared traits (sub-phenotypes) is an unmet need that could allow patient stratification for clinical management and research. We aimed to test the hypothesis that clinically-relevant sub-phenotypes can be reproducibly identified amongst patients with SAB. METHODS: We studied three cohorts of hospitalised adults with monomicrobial SAB: a UK retrospective observational study (Edinburgh cohort, n=458), the UK ARREST randomised trial (n=758), and the Spanish SAFO randomised trial (n=214). Latent class analysis was used to identify sub-phenotypes using routinely-collected clinical data, without considering outcomes. Mortality and microbiologic outcomes were then compared between sub-phenotypes. RESULTS: Included patients had predominantly methicillin-susceptible SAB (1366/1430,95.5%). We identified five distinct, reproducible clinical sub-phenotypes: (A) SAB associated with older age and comorbidity, (B) nosocomial intravenous catheter-associated SAB in younger people without comorbidity, (C) community-acquired metastatic SAB, (D) SAB associated with chronic kidney disease, and (E) SAB associated with injection drug use. Survival and microbiologic outcomes differed between the sub-phenotypes. 84-day mortality was highest in sub-phenotype A, and lowest in B and E. Microbiologic outcomes were worse in sub-phenotype C. In a secondary analysis of the ARREST trial, adjunctive rifampicin was associated with increased 84-day mortality in sub-phenotype B and improved microbiologic outcomes in sub-phenotype C. CONCLUSIONS: We have identified reproducible and clinically-relevant sub-phenotypes within SAB, and provide proof-of-principle of differential treatment effects. Through clinical trial enrichment and patient stratification, these sub-phenotypes could contribute to a personalised medicine approach to SAB.

NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

Sex-Specific Effects of Plastic Caging in Murine Viral Myocarditis.

BACKGROUND: Myocarditis is an inflammatory heart disease caused by viral infections that can lead to heart failure, and occurs more often in men than women. Since animal studies have shown that myocarditis is influenced by sex hormones, we hypothesized that endocrine disruptors, which interfere with natural hormones, may play a role in the progression of the disease. The human population is exposed to the endocrine disruptor bisphenol A (BPA) from plastics, such as water bottles and plastic food containers. METHODS: Male and female adult BALB/c mice were housed in plastic versus glass caging, or exposed to BPA in drinking water versus control water. Myocarditis was induced with coxsackievirus B3 on day 0, and the endpoints were assessed on day 10 post infection. RESULTS: We found that male BALB/c mice that were exposed to plastic caging had increased myocarditis due to complement activation and elevated numbers of macrophages and neutrophils, whereas females had elevated mast cell activation and fibrosis. CONCLUSIONS: These findings show that housing mice in traditional plastic caging increases viral myocarditis in males and females, but using sex-specific immune mechanisms.

Ethnic Differences in 90-Day Poststroke Medication Adherence.

Background and Purpose- We assessed ethnic differences in medication adherence 3 months poststroke in a population-based study as an initial step in investigating the increased stroke recurrence risk in Mexican Americans compared with non-Hispanic whites. Methods- Ischemic stroke cases from 2008 to 2015 from the Brain Attack Surveillance in Corpus Christi project in Texas were followed prospectively for 3 months poststroke to assess medication adherence. Medications in 5 drug classes were analyzed: statins, antiplatelets, anticoagulants, antihypertensives, and antidepressants. For each drug class, patients were considered adherent if they reported never missing a dose in a typical week. The χ2 tests or Kruskal-Wallis nonparametric tests were used for ethnic comparisons of demographics, risk factors, and medication adherence. A multivariable logistic regression model was constructed for the association of ethnicity and medication nonadherence. Results- Mexican Americans (n=692) were younger (median 65 years versus 68 years, P<0.001), had more diabetes mellitus ( P<0.001) and hypertension ( P<0.001) and less atrial fibrillation ( P=0.003), smoking ( P=0.003), and education ( P<0.001) than non-Hispanic whites (n=422). Sex, insurance status, high cholesterol, previous stroke/transient ischemic attack history, excessive alcohol use, tPA (tissue-type plasminogen activator) treatment, National Institutes of Health Stroke Scale score, and comorbidity index did not significantly differ by ethnicity. There was no significant difference in medication adherence for any of the 5 drug classes between Mexican Americans and non-Hispanic whites. Conclusions- This study did not find ethnic differences in medication adherence, thus challenging this patient-level factor as an explanation for stroke recurrence disparities. Other reasons for the excessive stroke recurrence burden in Mexican Americans, including provider and health system factors, should be explored.

Evidence from plutonic xenoliths for magma differentiation, mixing and storage in a volatile-rich crystal mush beneath St. Eustatius, Lesser Antilles.

Quantifying the storage conditions and evolution of different magmatic components within sub-volcanic plumbing systems is key to our understanding of igneous processes and products. Whereas erupted magmas represent a portion of the eruptible volcanic system, plutonic xenoliths provide a complementary record of the mushy roots of the plumbing system that cannot be mobilised easily to form lavas and consequently offer a unique record of magma diversity within the sub-volcanic plumbing system. Here, we present a detailed petrological and geochemical study of erupted plutonic xenoliths from the island of Sint Eustatius (Statia), in the northern Lesser Antilles volcanic arc. The plutonic xenoliths are predominantly gabbroic, but vary in texture, mineral assemblage and crystallisation sequence. We report major, trace and volatile (H2O and CO2) concentrations of xenolith-hosted melt inclusions (MIs) and interstitial glass. The MIs have a very large range in major element (49-78 wt% SiO2 and 0.1-6.1 wt% MgO) and trace element concentration (72-377 ppm Sr, 32-686 ppm Ba, 39-211 ppm Zr). Their chemistry varies systematically with host phase and sample type. Significantly, it shows that (1) plutonic xenoliths record a complete differentiation sequence from basalt to rhyolite (2) apatite, but not zircon, saturation was reached during crystallisation, (3) amphibole breakdown reactions play a role in the genesis of shallow gabbronorite assemblages, and (4) mixing between crystal cargos and multiple discrete bodies occurred. Residual melt volatile contents are high (≤ 9.1 wt% H2O and ≤ 1350 ppm CO2), returning volatile saturation pressures of 0-426 MPa. Multiple reaction geobarometry and experimental comparisons indicate that equilibration took place in the upper-middle crust (0-15 km). We infer that the Statia plutonic xenoliths represent portions of a large heterogeneous crystal mush within which a great diversity of melts was stored and mixed prior to eruption. Our data show that compositional variations in magmatic plumbing systems exceed those observed in volcanic products, a likely consequence of the blending that occurs prior to and during eruption.

Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites.

Biological polymers such as nucleic acids and proteins are constructed of only one-the d or l-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System's earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life's carbohydrate-related biopolymers.

Evaluation of intra-operative imaging during scarf osteotomy - an unnecessary cost or an essential prerequisite?

Scarf osteotomy is an effective surgical treatment option for hallux valgus. It can manipulate alignment in three planes, allowing accurate anatomical correction. The potential benefit of intra-operative image intensification (II) to gauge deformity correction during surgery however, has not been quantitatively reported. This study aims to compare the correction of hallux valgus by scarf osteotomy with and without intra-operative imaging. Retrospective analysis of a consecutive series of scarf osteotomy in 2 groups. Group A had intra-operative radiographic assessment and group B did not. Patient and surgical data was collected with a mean follow-up of 14 months. Of 99 scarf osteotomies there was no significant difference in age, gender or pre-operative deformity between the groups (p<0.05). No statistical difference was found between the radiographic corrections of the two groups (p<0.05), although operating time was less in group B. This series shows that intra-operative imaging does not improve accuracy of deformity correction, or implant position in scarf osteotomy. We suggest it is not required routinely during scarf osteotomy.

Severe Pulmonary Vein Stenosis Resulting From Ablation for Atrial Fibrillation: Presentation, Management, and Clinical Outcomes.

BACKGROUND: The frequency of pulmonary vein stenosis (PVS) after ablation for atrial fibrillation has decreased, but it remains a highly morbid condition. Although treatment strategies including pulmonary vein dilation and stenting have been described, the long-term impacts of these interventions are unknown. We evaluated the presentation of severe PVS, and examined the risk for restenosis after intervention using either balloon angioplasty (BA) alone or BA with stenting. METHODS: This was a prospective, observational study of 124 patients with severe PVS evaluated between 2000 and 2014. RESULTS: All 124 patients were identified as having severe PVS by computed tomography in 219 veins. One hundred two patients (82%) were symptomatic at diagnosis. The most common symptoms were dyspnea (67%), cough (45%), fatigue (45%), and decreased exercise tolerance (45%). Twenty-seven percent of patients experienced hemoptysis. Ninety-two veins were treated with BA, 86 were treated with stenting, and 41 veins were not treated. A 94% acute procedural success rate was observed and did not differ by initial management. Major procedural complications occurred in 4 of the 113 patients (3.5%) who underwent invasive assessment, and minor complications occurred in 15 patients (13.3%). Overall, 42% of veins developed restenosis including 27% of veins (n=23) treated with stenting and 57% of veins (n=52) treated with BA. The 3-year overall rate of restenosis was 37%, with 49% of BA-treated veins and 25% of stented veins developing restenosis (hazard ratio, 2.77; 95% confidence interval, 1.72-4.45; P<0.001). After adjustment for age, CHA2DS2-VASc score, hypertension, and the time period of the study, there was still a significant difference in the risk of restenosis for BA versus stenting (hazard ratio, 2.46; 95% confidence interval, 1.47-4.12; P<0.001). CONCLUSIONS: The diagnosis of PVS is challenging because of nonspecific symptoms and the need for dedicated pulmonary vein imaging. There is no difference in acute success by type of initial intervention; however, stenting significantly reduces the risk of subsequent pulmonary vein restenosis in comparison with BA.

Plutonic xenoliths from Martinique, Lesser Antilles: evidence for open system processes and reactive melt flow in island arc crust.

The Lesser Antilles Volcanic Arc is remarkable for the abundance and variety of erupted plutonic xenoliths. These samples provide a window into the deeper crust and record a more protracted crystallisation history than is observed from lavas alone. We present a detailed petrological and in situ geochemical study of xenoliths from Martinique in order to establish their petrogenesis, pre-eruptive storage conditions and their contribution to construction of the sub-volcanic arc crust. The lavas from Martinique are controlled by crystal-liquid differentiation. Amphibole is rarely present in the erupted lavas, but it is a very common component in plutonic xenoliths, allowing us to directly test the involvement of amphibole in the petrogenesis of arc magmas. The plutonic xenoliths provide both textural and geochemical evidence of open system processes and crystal 'cargos'. All xenoliths are plagioclase-bearing, with variable proportions of olivine, spinel, clinopyroxene, orthopyroxene and amphibole, commonly with interstitial melt. In Martinique, the sequence of crystallisation varies in sample type and differs from other islands of the Lesser Antilles arc. The compositional offset between plagioclase (~An90) and olivine (~Fo75), suggests crystallisation under high water contents and low pressures from an already fractionated liquid. Texturally, amphibole is either equant (crystallising early in the sequence) or interstitial (crystallising late). Interstitial amphibole is enriched in Ba and LREE compared with early crystallised amphibole and does not follow typical fractionation trends. Modelling of melt compositions indicates that a water-rich, plagioclase-undersaturated reactive melt or fluid percolated through a crystal mush, accompanied by the breakdown of clinopyroxene, and the crystallisation of amphibole. Geothermobarometry estimates and comparisons with experimental studies imply the majority of xenoliths formed in the mid-crust. Martinique cumulate xenoliths are inferred to represent crystal mushes within an open system, through which melt can both percolate and be generated.

Lower Extremity Deformity Management in MPS IVA, Morquio-Brailsford Syndrome: Preliminary Report of Hemiepiphysiodesis Correction of Genu Valgum.

BACKGROUND: Morquio-Brailsford syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an inherited metabolic disease in which skeletal deformities can be extreme. An international registry has shown that 46% of patients are unable to walk 200 m and 30% use a wheelchair. Lower limb surgery is performed to restore alignment with the expectation of maintaining mobility. We are, however, not aware of reports correlating function with alignment. This study assesses the role of orthopaedic intervention with reference to anatomic and functional outcome in MPS IV-A: specifically hemiepiphysiodesis correction of genu valgum. METHODS: Interrogation of the MPS patient database identified 63 patients. Patient demographic and radiographic data were collected along with information on deformity, correction, mobility, and genotype. Genu valgum was assessed by intermalleolar distance and mobility by a standardized 6-minute walk test. Sequential hip anatomy was assessed radiographically. RESULTS: Twenty-six surgical hemiepiphysiodesis episodes were performed on 23 patients. There were no cases of implant failure, loosening, or infection. The average intermalleolar distance reduction was 6.12 cm (paired t test, P=0.0001) (95% confidence interval, 7.6-4.7 cm) and the mean change in 6-minute walk test was +69.5 m (P=0.0339). There was no correlation between hip subluxation/dislocation and mobility (Fisher exact test, P=1.000), although hip parameters deteriorated over time. Three patients required repeat 8-plate insertion and 1 a femoral osteotomy. CONCLUSIONS: Eight-plate hemiepiphysiodesis correction of genu valgum in MPS IV-A is an effective treatment with low complication rates. The insult of surgery is minimal compared with that of osteotomy which can reduce mobility further. Our outcomes suggest that mobility is maintained or improved even in severe genotypes where mobility typically worsens. We have found hip pathology to be less debilitating, but further studies are needed to assess the effect of genu valgum correction upon femoral head subluxation and collapse.We suggest hemiepiphysiodesis should be considered as part of the treatment strategy for limb alignment in MPS IV-A patients, depending on remaining growth, mobility status, and genotype. LEVEL OF EVIDENCE: Level IV-therapeutic case series.

Can a Silver-Coated Arthrodesis Implant Provide a Viable Alternative to Above Knee Amputation in the Unsalvageable, Infected Total Knee Arthroplasty?

BACKGROUND: In the unsalvageable, infected total knee arthroplasty, knee arthrodesis is one treatment option with lower reported reinfection rates compared with repeated 2-stage revision and improved function compared with amputation. One possible method for reducing incidence of recurrent infection treated by arthrodesis is the use of a silver-coated implant. We report our experience of silver-coated arthrodesis nails used for managing infected revision arthroplasty. We primarily assess the rate of reinfection and rate of amputation and report functional outcome measures. METHODS: Retrospective analysis of all patients undergoing knee arthrodesis with a silver-coated arthrodesis nail between 2008 and 2014. Patient-reported data were recorded prearthrodesis and postarthrodesis (Oxford Knee Score and Short Form-36) as well as evidence of recurrent of infection, subsequent surgery, and the necessity for amputation. RESULTS: Eight patients underwent arthrodesis using the silver-coated arthrodesis nail. Mean duration of follow-up was 16 months (5-35 months). At the point of follow-up, there were no amputations, deaths, or implant revisions. One case of recurrent infection was successfully treated with washout and debridement. The mean prearthrodesis and postarthrodesis Oxford Knee Score difference was +8.9 points (P = .086) with significantly improved pain (P = .019), night pain (P = .021), and ease of standing (P = .003). CONCLUSION: Arthrodesis of the knee using a silver-coated intramedullary device is successful in eradicating infection and allowing limb conservation. Where infection does recur, this can be successfully treated with implant retention. The use of a silver-coated arthrodesis nail should be considered as an alternative to amputation for patients with a multiply revised and infected total knee arthroplasty.

Detection and formation scenario of citric acid, pyruvic acid, and other possible metabolism precursors in carbonaceous meteorites.

Carbonaceous meteorites deliver a variety of organic compounds to Earth that may have played a role in the origin and/or evolution of biochemical pathways. Some apparently ancient and critical metabolic processes require several compounds, some of which are relatively labile such as keto acids. Therefore, a prebiotic setting for any such individual process would have required either a continuous distant source for the entire suite of intact precursor molecules and/or an energetic and compact local synthesis, particularly of the more fragile members. To date, compounds such as pyruvic acid, oxaloacetic acid, citric acid, isocitric acid, and α-ketoglutaric acid (all members of the citric acid cycle) have not been identified in extraterrestrial sources or, as a group, as part of a "one pot" suite of compounds synthesized under plausibly prebiotic conditions. We have identified these compounds and others in carbonaceous meteorites and/or as low temperature (laboratory) reaction products of pyruvic acid. In meteorites, we observe many as part of three newly reported classes of compounds: keto acids (pyruvic acid and homologs), hydroxy tricarboxylic acids (citric acid and homologs), and tricarboxylic acids. Laboratory syntheses using (13)C-labeled reactants demonstrate that one compound alone, pyruvic acid, can produce several (nonenzymatic) members of the citric acid cycle including oxaloacetic acid. The isotopic composition of some of the meteoritic keto acids points to interstellar or presolar origins, indicating that such compounds might also exist in other planetary systems.

Ultrasound Measurement of Femoral Articular Cartilage Thickness Before and After Marathon Running.

OBJECTIVE: The purpose of this study was to use ultrasonography to measure femoral articular cartilage thickness changes during marathon running, which could support MRI studies showing that deformation of knee cartilage during long-distance running is no greater than that for other weight-bearing activities. MATERIALS AND METHODS: Participants included 38 marathon runners with no knee pain or history of knee injury, aged 18-39. Ultrasound images of the femoral articular cartilage were taken two hours before and immediately after the race. Femoral articular cartilage thickness was measured at both the medial and lateral femoral condyles. RESULTS: The maximum change in femoral articular cartilage thickness, measured at the left outer lateral femoral condyle, was 6.94% (P=.006). All other femoral articular cartilage thickness changes were not significant. CONCLUSION: A change in femoral articular cartilage thickness of 6.94% supports our hypothesis that long-distance running does not induce deformational changes greater than that of regular daily activities. This study using ultrasonography supports MRI evidence that knee cartilage tolerates marathon running well.

Sleep and the Young Athlete.

CONTEXT: Sleep plays a vital role in cognitive and physical performance. Teenage athletes (ages 13-19 years) are considered especially at risk for disordered sleep and associated negative cognitive, physical, and psychosomatic effects. However, there is a paucity of evidence-based recommendations to promote sleep quality and quantity in athletes who fall within this age range. We performed a review of the literature to reveal evidence-based findings and recommendations to help sports instructors, athletic trainers, physical therapists, physicians, and other team members caring for young athletes provide guidance on sleep optimization for peak sports performance and injury risk reduction. METHODS: PubMed, Scopus, and Cochrane CENTRAL were searched on May 11, 2016, and then again on September 1, 2020, for relevant articles published to date. STUDY DESIGN: Narrative review. LEVEL OF EVIDENCE: Level 4. RESULTS: Few studies exist on the effects disordered sleep may have on teenage athletes. By optimizing sleep patterns in young athletes during training and competitions, physical and mental performance, and overall well-being, may be optimized. Adequate sleep has been shown to improve the performance of athletes, although further studies are needed. CONCLUSION: Twenty-five percent of total sleep time should be deep sleep, with a recommended sleep time of 8 to 9 hours for most young athletes. Screen and television use during athletes' bedtime should be minimized to improve sleep quality and quantity. For young athletes who travel, jet lag can be minimized by allowing 1 day per time zone crossed for adjustment, limiting caffeine intake, planning meals and onboard sleeping to coincide with destination schedules, timing arrivals in the morning whenever possible, and using noise-canceling headphones and eyeshades. STRENGTH-OF-RECOMMENDATION TAXONOMY (SORT): B.

Slab to back-arc to arc: Fluid and melt pathways through the mantle wedge beneath the Lesser Antilles.

Volatiles expelled from subducted plates promote melting of the overlying warm mantle, feeding arc volcanism. However, debates continue over the factors controlling melt generation and transport, and how these determine the placement of volcanoes. To broaden our synoptic view of these fundamental mantle wedge processes, we image seismic attenuation beneath the Lesser Antilles arc, an end-member system that slowly subducts old, tectonized lithosphere. Punctuated anomalies with high ratios of bulk-to-shear attenuation (Qκ-1/Qµ-1 > 0.6) and VP/VS (>1.83) lie 40 km above the slab, representing expelled fluids that are retained in a cold boundary layer, transporting fluids toward the back-arc. The strongest attenuation (1000/QS ~ 20), characterizing melt in warm mantle, lies beneath the back-arc, revealing how back-arc mantle feeds arc volcanoes. Melt ponds under the upper plate and percolates toward the arc along structures from earlier back-arc spreading, demonstrating how slab dehydration, upper-plate properties, past tectonics, and resulting melt pathways collectively condition volcanism.