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Jockeys are unique given that they make weight daily and, therefore, often resort to fasting and dehydration. Through increasing daily food frequency (during energy deficit), we have reported short-term improvements in jockey’s body composition. While these changes were observed over 6–12 weeks with food provided, it is unclear whether such improvements can be maintained over an extended period during free-living conditions. We, therefore, assessed jockeys over 5 years using dual X-ray absorptiometry, resting metabolic rate, and hydration measurements. Following dietary and exercise advice, jockeys reduced fat mass from baseline of 7.1 ± 1.4 kg to 6.1 ± 0.7 kg and 6.1 ± 0.6 kg (p p p p = .009) and 87% (p = .003) at Years 1 and 5, alongside regular lunch from 35% to 92% (p p

Representative macroscopic images of a sample are an integral part of many material testing methods. Usually, a digital camera attached to a macro stand is used. Recurring problems include reflections from the surface of the sample or the fact that regular 2D representations of fracture surfaces, for example, do not always permit a correct interpretation at a later point. In this study, a novel objective lens from K|Lens GmbH, capable of recording the depth information of the surface with a digital camera in a single shot and enabling three-dimensional reconstruction will be used to evaluate potential applications. Furthermore, application limits in macroscopic imaging and the analysis of typical metallographic samples, with the focus being on three-dimensional imaging and quantification, will be studied.

The circuit origins of aggression in autism spectrum disorder remain undefined. Here we reportTac1-expressing glutamatergic neurons in ventrolateral division of ventromedial hypothalamus (VMHvl) drive intermale aggression. Aggression is increased due to increases ofUbe3agene dosage in the VMHvl neurons when modeling autism due to maternal 15q11-13 triplication. Targeted deletion of increasedUbe3acopies in VMHvl reverses the elevated aggression adult mice. VMHvl neurons form excitatory synapses onto hypothalamic arcuate nucleus AgRP/NPY neurons through a NRXN1-CBLN1-GluD1 transsynaptic complex and UBE3A impairs this synapse by decreasingCbln1gene expression. Exciting AgRP/NPY arcuate neurons leads to feedback inhibition of VMHvl neurons and inhibits aggression. Asymptomatic increases of UBE3A synergize with a heterozygous deficiency of presynapticNrxn1or postsynapticGrid1(both ASD genes) to increase aggression. Targeted deletions ofGrid1in arcuate AgRP neurons impairs the VMHvl to AgRP/NPY neuron excitatory synapses while increasing aggression. Chemogenetic/optogenetic activation of arcuate AgRP/NPY neurons inhibits VMHvl neurons and represses aggression. These data reveal that multiple autism genes converge to regulate the VMHvl-arcuate AgRP/NPY glutamatergic synapse. The hypothalamic circuitry implicated by these data suggest impaired excitation of AgRP/NPY feedback inhibitory neurons may explain the increased aggression behavior found in genetic forms of autism.One Sentence SummaryA feedback circuit in the hypothalamus that inhibits aggression is impaired by converging autism genetic defects.

Accurate modeling of the complex electronic structure of actinide complexes requires full inclusion of relativistic effects. In this study, we examine the effect of explicit inclusion of spin-orbit coupling (SOC) versus scalar relativistic effects on the predicted spectra for heavy-element complexes. In this study, we employ a relativistic two-component Hamiltonian in the X2C form with all of the electrons in the system being considered explicitly to compare and contrast with previous studies that included the relativistic effects by means of relativistic effective core potentials (RECPs). A few uranium complexes are chosen as model systems. Comparison of the computed Cl K-edge X-ray absorption spectra with experimental data shows significantly improved agreement when a variational relativistic treatment of SOC is performed. In particular, we note the importance of SOC terms to obtain not only correct transition energies but also correct intensities for these heavy-element complexes because of the redistribution of ligand bonding character among the valence MOs. While RECPs generally agree well with all-electron scalar relativistic calculations, there are some differences in the predicted spectra of open-shell systems. These methods are still suitable for broad application to analyze the qualitative nature of transitions in X-ray absorption spectra, but caution is recommended for quantitative analysis, as SOC can be non-negligible for both open- and closed-shell heavy-element systems.

Primary stereotactic radiosurgery for intraventricular meningiomas remains controversial owing to the potential for life-threatening peritumoral edema and lack of long-term follow-up data. We review the literature and present the largest series to assess efficacy and safety of primary stereotactic radiosurgery.A systematic review of the literature for primary stereotactic radiosurgery for intraventricular meningiomas was conducted. The retrospective series presented here comprised 33 patients who received primary stereotactic radiosurgery between 1999 and 2015 for a radiologically detected intraventricular meningioma. Demographic, diagnostic, and therapeutic data were extracted from medical records, imaging, and treatment-planning systems. Both standalone and pooled analysis were performed.The mean patient age was 53 years, and 24 patients (73%) were female. The median Karnofsky performance status pretreatment was 80 (range, 60-100). The majority of lesions were located in the lateral ventricles (n = 32; 97%). The mean tumor volume was 8.7 cmPrimary stereotactic radiosurgery for intraventricular meningiomas shows excellent treatment efficacy and low toxicity in patients with a long follow-up period. The best therapeutic algorithm remains to be established leveraging further clinical investigation.

Purpose Interstitial brachytherapy based on phosphorus-32 (P-32) has an established role as a minimally invasive treatment modality for patients with cystic craniopharyngioma. However, reporting on long-term outcomes with toxicity profiles for large cohorts is lacking in the literature. The purpose of this study is therefore to evaluate the long-term visual, endocrinal, and neurocognitive functions in what is the largest patient series having received this treatment to date. Methods and Materials We retrospectively evaluated 90 patients with cystic craniopharyngiomas who were treated with stereotactic intracavitary brachytherapy between 1998 and 2010. Colloidal activity of injected radioisotope P-32 was based on an even distribution within the tumor. After treatment, patients were followed-up for a minimum of 5 years and over a mean of 121 months (60-192 months) to assess radiographic and clinical responses. Results The 90 patients included in our study cohort underwent a total of 108 stereotactic surgical procedures for 129 craniopharyngioma-related cysts. Of the included tumors, 65 (72.2%) were associated with a single cyst, 15 (16.7%) were associated with 2 cysts, and 10 (11.1%) tumors had developed septations with 3 to 4 cysts. Stereotactic cyst puncture and content aspiration were used to drain a mean cyst fluid volume of 21.4 mL (1.0-55.0 mL). Each cyst was then instilled for interstitial brachytherapy with colloidal P-32 solution. Based on radiographic follow-up assessments, 56 cysts (43.4%) showed resolution and/or nonrecurrence, which was classified as a complete response to treatment; 47 cysts (36.4%) showed a partial response; and 5 cysts (3.9%) displayed a stable appearance. Treatment resulted in immediate and clinically significant vision improvement in 54 of 63 (86%) symptomatic patients, and this improvement was maintained. Progression-free survival rates at 5 and 10 years were 95.5% and 84.4%, respectively. Conclusions P-32–based interstitial brachytherapy can play an effective role in managing patients with cystic craniopharyngiomas. It can be considered a valid alternative to surgery in select patients with a favorable toxicity profile and long-term clinical outcomes.

Meningioma is the most common primary central nervous system tumor. Although mostly nonmalignant, meningioma can cause serious complications by mass effect and vasogenic edema. While surgery and radiation improve outcomes, not all cases can be treated due to eloquent location. Presently no medical treatment is available to slow meningioma growth owing to incomplete understanding of the underlying pathology, which in turn is due to the lack of high-fidelity tissue culture and animal models. We propose a simple and rapid method for the establishment of meningioma tumor-derived primary cultures. These cells can be maintained in culture for a limited time in serum-free media as spheres and form adherent cultures in the presence of 4% fetal calf serum. Many of the tissue samples show expression of the lineage marker PDG2S, which is typically retained in matched cultured cells, suggesting the presence of cells of arachnoid origin. Furthermore, nonarachnoid cells including vascular endothelial cells are also present in the cultures in addition to arachnoid cells, potentially providing a more accurate tumor cell microenvironment, and thus making the model more relevant for meningioma research and high-throughput drug screening.

Triggered by a recent article establishing the surprising result that within the class of bivariate Archimedean copulas 𝒞ardifferent notions of convergence - standard uniform convergence, convergence with respect to the metricD1, and so-called weak conditional convergence - coincide, in the current contribution we tackle the natural question, whether the obtained equivalence also holds in the larger class of associative copulas 𝒞a. Building upon the fact that each associative copula can be expressed as (finite or countably infinite) ordinal sum of Archimedean copulas and the minimum copulaMwe show that standard uniform convergence and convergence with respect toD1are indeed equivalent in 𝒞a. It remains an open question whether the equivalence also extends to weak conditional convergence. As by-products of some preliminary steps needed for the proof of the main result we answer two conjectures going back to Durante et al. and show that, in the language of Baire categories, when working withD1a typical associative copula is Archimedean and a typical Archimedean copula is strict.

Context. HR 8799 is a young planetary system composed of four planets and a double debris belt. Being the first multi-planetary system discovered with the direct imaging technique, it has been observed extensively since 1998. This wide baseline of astrometric measurements, counting over 50 observations in 20 years, permits a detailed orbital and dynamical analysis of the system. Aims. To explore the orbital parameters of the planets, their dynamical history, and the planet-to-disk interaction, we made follow-up observations of the system during the VLT/SPHERE guaranteed time observation program. We obtained 21 observations, most of them in favorable conditions. In addition, we observed HR 8799 with the instrument LUCI at the Large Binocular Telescope (LBT). Methods. All the observations were reduced with state-of-the-art algorithms implemented to apply the spectral and angular differential imaging method. We re-reduced the SPHERE data obtained during the commissioning of the instrument and in three open-time programs to have homogeneous astrometry. The precise position of the four planets with respect to the host star was calculated by exploiting the fake negative companions method. We obtained an astrometric precision of the order of 6 mas in the worst case and 1 mas in the best case. To improve the orbital fitting, we also took into account all of the astrometric data available in the literature. From the photometric measurements obtained in different wavelengths, we estimated the masses of the planets following the evolutionary models. Results. We obtained updated parameters for the orbits with the assumption of coplanarity, relatively small eccentricities, and periods very close to the 2:1 resonance. We also refined the dynamical mass of each planet and the parallax of the system (24.49 +/- 0.07 mas), which overlap with the recent Gaia eDR3/DR3 estimate. Hydrodynamical simulations suggest that inward migration of the planets caused by the interaction with the disk might be responsible for the planets being locked in resonance. We also conducted detailed N-body simulations indicating possible positions of a putative fifth planet with a mass below the present detection limits of similar or equal to 3 M-Jup., Astronomy & Astrophysics, 666, ISSN:0004-6361, ISSN:1432-0746

The preparation of metallographic sections from soft metals such as pure copper constitutes a particular challenge: the high degree of ductility promotes the formation of preparation artifacts and complicates the preparation of homogeneous, low-deformation surfaces. A metallographic preparation routine is therefore presented which has proven effective for pure copper and which can also be applied to additionally soft annealed samples. The subsequent removal of fine crystalline deformation layers is discussed and different setups for electropolishing and its optimization are presented.

Context. The direct imaging of potentially habitable exoplanets is one prime science case for the next generation of high contrast imaging instruments on ground-based, extremely large telescopes. To reach this demanding science goal, the instruments are equipped with eXtreme Adaptive Optics (XAO) systems which will control thousands of actuators at a framerate of kilohertz to several kilohertz. Most of the habitable exoplanets are located at small angular separations from their host stars, where the current control laws of XAO systems leave strong residuals. Aims. Current AO control strategies such as static matrix-based wavefront reconstruction and integrator control suffer from a temporal delay error and are sensitive to mis-registration, that is, to dynamic variations of the control system geometry. We aim to produce control methods that cope with these limitations, provide a significantly improved AO correction, and, therefore, reduce the residual flux in the coronagraphic point spread function (PSF). Methods. We extend previous work in reinforcement learning for AO. The improved method, called the Policy Optimization for Adaptive Optics (PO4AO), learns a dynamics model and optimizes a control neural network, called a policy. We introduce the method and study it through numerical simulations of XAO with Pyramid wavefront sensor (PWFS) for the 8-m and 40-m telescope aperture cases. We further implemented PO4AO and carried out experiments in a laboratory environment using Magellan Adaptive Optics eXtreme system (MagAO-X) at the Steward laboratory. Results. PO4AO provides the desired performance by improving the coronagraphic contrast in numerical simulations by factors of 3–5 within the control region of deformable mirror and PWFS, both in simulation and in the laboratory. The presented method is also quick to train, that is, on timescales of typically 5–10 s, and the inference time is sufficiently small (

Neuroimaging modalities such as computer tomography and magnetic resonance imaging have greatly improved in their ability to achieve higher spatial resolution of neurovascular and soft tissue neuroanatomy, allowing for increased accuracy in the diagnosis of neurological conditions. However, the use of conventional contrast agents that have short tissue retention time and associated renal toxicities, or expensive radioisotope tracers that are not widely available, continue to limit the sensitivity of these imaging modalities. Nanoparticles can potentially address these shortcomings by enhancing tissue retention and improving signal intensity in the brain and neural axis. In this review, we discuss the use of different types of nanotechnology to improve the detection, diagnosis, and treatment of a wide range of neurological diseases.

Elevated intracranial pressure due to cerebral edema is associated with very poor survival in patients with acute liver failure (ALF). Placing an intracranial pressure monitor (ICPm) aids in management of intracranial hypertension, but is associated with potentially fatal hemorrhagic complications related to the severe coagulopathy associated with ALF. An institutional Acute Liver Failure Clinical Protocol (ALF-CP) was created to correct ALF coagulopathy prior to placing parenchymal ICP monitoring bolts. We aimed to investigate the frequency, severity, and clinical significance of hemorrhagic complications associated with ICPm bolt placement in the setting of an ALF-CP. All assessed patients were managed with the ALF-CP and had rigorous radiologic follow-up allowing assessment of the occurrence and chronology of hemorrhagic complications. We also aimed to compare our outcomes to other studies that were identified through a comprehensive review of the literature. Fourteen ALF patients were included in our analysis. There was no symptomatic hemorrhage after ICP monitor placement though four patients were found to have minor intraparenchymal asymptomatic hemorrhages after liver transplant when the ICP monitor had been removed, making the rate of radiographically identified clinically asymptomatic hemorrhage 28.6%. These results compare favorably to those found in a comprehensive review of the literature which revealed rates as high as 17.5% for symptomatic hemorrhages and 30.4% for asymptomatic hemorrhage. This study suggests that an intraparenchymal ICPm can be placed safely in tertiary referral centers which utilize a protocol such as the ALF-CP that aggressively corrects coagulopathy. The ALF-CP led to advantageous outcomes for ICPm placement with a 0% rate of symptomatic and low rate of asymptomatic hemorrhagic complications, which compares well to results reported in other series. A strict ICPm placement protocol in this setting facilitates management of ALF patients with cerebral edema during the wait time to transplantation or spontaneous recovery.

Objective:Patients with pregnancy-associated secondary brain tumors (PASBT) are challenging to manage. Because no guidelines for the management of such patients currently exist, we performed a systematic review of the literature using PRISMA guidelines with a discussion of management from a neurosurgeon’s perspective.Method:Systematic review of the literature using PRISMA guidelines from 1999 to 2018.Results:We identified 301 studies of which 16 publications (22 patients reporting 25 pregnancies, 20 deliveries, 5 early terminations) were suitable for final analysis. The most frequent primary cancers were breast (8/22, 36.36%), skin (6/22, 27.27%), and lung (5/22, 22.73%). Four patients (18.18%) had neurosurgical procedures during their pregnancies. Five patients (22.73%) received neurosurgical resection after their pregnancies. Nine patients (40.91%) received radiation therapy and seven patients (31.82%) received chemotherapy during pregnancy while seven patients (31.82%) received chemotherapy and radiation after pregnancy. There was 1 fetal death (5%) out of 20 healthy deliveries. Five pregnancies (20%) were terminated in the first trimester due to a need for urgent neurosurgical intervention.Conclusion:Management of PASBT remains a challenging issue. Maternal and fetal risks associated with surgical resection and teratogenicity due to adjuvant therapy should be discussed in the context of a multidisciplinary team. Timing of surgery and the use of systemic chemoradiation depends on the gestational age (GA) of the fetus, extent, and control of the mother’s primary and metastatic disease. Guidelines need to be established to help neuro-oncology teams safely and effectively manage this group of patients.

Radiation therapy (RT) is a mainstay for the treatment of pediatric brain tumors. As improvements in and sophistication of this modality continue to increase the survival of patients, the long-term sequelae of RT pose significant challenges in the clinical management of this patient population as they transition into adulthood. In this special edition, we review the short- and long-term effects of RT for the treatment of pediatric brain tumors and the necessary surveillance required for follow-up.

Neuronal growth regulator 1 (NEGR1) and neurotrimin (NTM) are abundant cell-surface proteins found in the brain and form part of the IgLON (Immunoglobulin LSAMP, OBCAM, Neurotrimin) family. In humans, NEGR1 is implicated in obesity and mental disorders, while NTM is linked to intelligence and cognitive function. IgLONs dimerize homophilically and heterophilically, and they are thought to shape synaptic connections and neural circuits by acting in trans (spanning cellular junctions) and/or in cis (at the same side of a junction). Here, we reveal homodimeric structures of NEGR1 and NTM. They assemble into V-shaped complexes via their Ig1 domains, and disruption of the Ig1–Ig1 interface abolishes dimerization in solution. A hydrophobic ridge from one Ig1 domain inserts into a hydrophobic pocket from the opposing Ig1 domain producing an interaction interface that is highly conserved among IgLONs but remarkably plastic structurally. Given the high degree of sequence conservation at the interaction interface, we tested whether different IgLONs could elicit the same biological effect in vivo. In a small-scale study administering different soluble IgLONs directly into the brain and monitoring feeding, only NEGR1 altered food intake significantly. Taking NEGR1 as a prototype, our studies thus indicate that while IgLONs share a conserved mode of interaction and are able to bind each other as homomers and heteromers, they are structurally plastic and can exert unique biological action.

Rugby is characterized by frequent high-intensity collisions, resulting in muscle soreness. Players consequently seek strategies to reduce soreness and accelerate recovery, with an emerging method being cannabidiol (CBD), despite anti-doping risks. The prevalence and rationale for CBD use in rugby has not been explored; therefore, we recruited professional male players to complete a survey on CBD. Goodness of fit chi-square (χ2) was used to assess CBD use between codes and player position. Effects of age on use were determined using χ2 tests of independence. Twenty-five teams provided 517 player responses. While the majority of players had never used CBD (p V = 0.24), 26% had either used it (18%) or were still using it (8%). Significantly more CBD use was observed in rugby union compared with rugby league (p = .004, V = 0.13), but player position was not a factor (p = .760, V = 0.013). CBD use increased with players’ age (p V = 0.28), with mean use reaching 41% in the players aged 28 years and older category (p

Pediatric patients suffering from cerebral nidal arteriovenous malformations are a unique population due to the rare occurrence of the disease. Diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children is a rare event and mainly restricted to coincidental detection from screening of possibly afflicted family members. In patients with HHT, it is well known that the incidence of cerebral vascular malformations (CVMs) is higher than expected when compared with the nonafflicted population. Even though CVMs comprise a variety of different distinct anatomical and radiographic entities (e.g., capillary telangiectasia, nidal arteriovenous malformation [AVM], cavernous malformation, dural or pial as well as mixed fistula, and vein of Galen malformation), they are mostly summarized and analyzed all in one category due to the low number of individual cases identified in single centers. Nevertheless, the best treatment algorithm will likely vary significantly between different CVMs as does the clinical presentation and the natural course of the CVM. It is therefore the objective of this article to focus on nidal AVMs in pediatric patients suffering from HHT. To this end, we performed a systematic selective literature research to estimate incidence, clinical and radiological appearance, as well as classification according to established grading system, and to evaluate the necessity of treatment of these lesions in light of their respective outcomes. Our line of arguments explains why we recommend to follow these lesions expectantly and suggest to keep pediatric patients under surveillance with sequential scans until they reach adulthood.

Even though shunt surgery has been an established and widely accepted treatment for congenital hydrocephalus for five decades, long-term follow-up and functional outcome data are scarce. Based on our experience, we advocate a very rigid follow-up regimen throughout life for every hydrocephalus patient encountered with individual screening intervals not longer than 1 year in childhood and adolescence and surveillance intervals of 2 years in adulthood. A continuous treatment of the patients at the primary institution that performed hydrocephalus surgery provides an optimal setting to be prepared for the detection of adverse events of shunt malfunctioning. However, some patients may still encounter catastrophic events resulting in persistent deficits or death.

Difficult-to-treat epilepsy is defined as ongoing seizures despite adequate pharmacological treatment. This condition is affecting a significant percentage of epilepsy patients and is estimated to be as high as one-third of all patients. Epilepsy surgery, targeting the removal of the key parts of cerebral convolutions responsible for seizure generation and often including a structural lesion, can be a very successful approach. However, this necessitates careful patient selection by comprehensive investigations, proving the localization of the epileptogenic zone as well as measures to make such surgeries safe. With careful selection as a prerequisite, the percentage of patients achieving seizure freedom by neurosurgical intervention is high, approximating two-thirds of all epilepsy surgeries performed. In contrast, the average duration of a patient's pharmacoresistant focal epilepsy prior to surgery anywhere around the globe is around 20 years. Given that typical patients are ∼30 to 40 years of age at the time of surgery, many patients have been living with chronic seizures since childhood or adolescence. This means that most of these patients have been going through several stages of medical care for years or even decades, both as children and adults, without ever being fully investigated and/or selected for surgery which is concerning. Yet, there is no set standard for a timeline leading toward successful surgery in epilepsy. It is obvious that the average transit period from the moment of first seizure manifestation until the day of successful surgery takes much too long. This is the reason why we see these patients lost in transition.

Background Pediatric craniocerebral gunshot injuries (CGIs) occur both in the context of accidental and intentional trauma. The incidence and physiology of pediatric CGIs merit reexamination of prognostic factors and treatment priorities. This study characterizes the current understanding of mortality and prognostic factors in this patient population. Methods A systematic search was conducted. Selection criteria included all studies published since 2000, which described civilian isolated CGIs in pediatric patients. Data were analyzed qualitatively and quantitatively to identify factors prognostic for the primary outcome of mortality. Secondary outcomes included functional outcome status, requirement for surgery, and injury complications. Study quality was assessed with the Newcastle-Ottawa Scale. This study was registered with PROSPERO (CRD42019134231). Results Initial search revealed 349 unique studies. Forty underwent full text screening, and eight studies were included in the final synthesis. The overall mortality rate was 44.8%. Most CGIs occurred in older teenagers. Aggressive surgical treatment was recommended by one author, while remaining studies emphasized clinical judgment. Reported prognostic factors include initial Glasgow Coma Scale, pupil reactivity, involvement of multiple lobes or deep nuclei, and bihemispheric injuries. Reported complications from CGIs included seizure, meningitis, abscess, cerebrospinal fluid leak, bullet migration, focal neurological deficits, endocrine abnormalities, cognitive deficits, and neuropsychological deficits. The Glasgow Outcome Scale was the predominant measure of function and demonstrated a moderate recovery in 17.4% and a good recovery in 27.3% of patients. Conclusion This systematic review analyzed the existing evidence for prognostic factors in the context of pediatric CGIs. Significant long-term clinical improvement is possible with interventions including urgent surgical therapy. Fixed bilateral pupils and low initial Glasgow Coma Scale correlate with mortality but do not predict all patient outcomes. Patients younger than 15 years are underreported and may have differences in outcome. The literature on pediatric CGIs is limited and requires further characterization. Level of evidence Systematic Review, level IV.

The COVID-19 pandemic in 2020 has resulted in widespread training disruption in many sports. Some athletes have access to facilities and equipment, while others have limited or no access, severely limiting their training practices. A primary concern is that the maintenance of key physical qualities (e. g. strength, power, high-speed running ability, acceleration, deceleration and change of direction), game-specific contact skills (e. g. tackling) and decision-making ability, are challenged, impacting performance and injury risk on resumption of training and competition. In extended periods of reduced training, without targeted intervention, changes in body composition and function can be profound. However, there are strategies that can dramatically mitigate potential losses, including resistance training to failure with lighter loads, plyometric training, exposure to high-speed running to ensure appropriate hamstring conditioning, and nutritional intervention. Athletes may require psychological support given the challenges associated with isolation and a change in regular training routine. While training restrictions may result in a decrease in some physical and psychological qualities, athletes can return in a positive state following an enforced period of rest and recovery. On return to training, the focus should be on progression of all aspects of training, taking into account the status of individual athletes.

The optimal management of Chiari I malformation during pregnancy remains uncertain. Labor contractions, which increase intracranial pressure, and neuraxial anesthesia both carry the theoretical risk of brainstem herniation given the altered CSF dynamics inherent to the condition. Mode of delivery and planned anesthesia, therefore, require forethought to avoid potentially life-threatening complications. Since the assumed potential risks are significant, we seek to systematically review published literature regarding Chiari I malformation in pregnancy and, therefore, to establish a best practice recommendation based on available evidence. The English-language literature was systematically reviewed from 1991 to 2018 according to PRISMA guidelines to assess all pregnancies reported in patients with Chiari I malformation. After analysis, a total of 34 patients and 35 deliveries were included in this investigation. Additionally, a single case from our institutional experience is presented for illustrative purposes but not included in the statistical analysis. No instances of brain herniation during pregnancy in patients with Chiari I malformation were reported. Cesarean deliveries (51%) and vaginal deliveries (49%) under neuraxial blockade and general anesthesia were both reported as safe and suitable modes of delivery. Across all publications, only one patient experienced a worsening of neurologic symptoms, which was only later discovered to be the result of a previously undiagnosed Chiari I malformation. Several patients underwent decompressive suboccipital craniectomy to treat the Chiari I malformation during the preconception period (31%), during pregnancy (3%), and after birth (6%). Specific data regarding maternal management were not reported for a large number (21) of these patients (60%). Aside from one abortion in our own institutional experience, there was no report of any therapeutic abortion or of adverse fetal outcome. Although devastating maternal complications are frequently feared, very few adverse outcomes have ever been reported in pregnant patients with a Chiari I malformation. The available evidence is, however, rather limited. Based on our survey of available data, we recommend vaginal delivery under neuraxial blockade for truly asymptomatic patients. Furthermore, based on our own experience and physiological conceptual considerations, we recommend limiting maternal Valsalva efforts either via Cesarean delivery under regional or general anesthesia or by choosing assisted vaginal delivery under neuraxial blockade. There is no compelling reason to offer suboccipital decompression for Chiari I malformation during pregnancy. For patients with significant neurologic symptoms prior to conception, decompression prior to pregnancy should be considered.

The multiconfiguration nature of late-row (≥4th) elements and their molecular complexes, combined with significant relativistic effects, present large challenges for the accurate description of their electronic structure. To address these challenges and incorporate both relativistic and electron correlation effects, we present a two-component Kramers-unrestricted multireference configuration interaction method where relativistic effects are included variationally at the molecular orbital level via use of the "exact two-component" transformation of the solution of the one-electron modified Dirac equation. This method is developed within the restricted active space framework, allowing flexibility in both the choice of correlation space and the level of truncation of the excitation operator, as well as promoting the efficiency of generating and book-keeping unique electronic configurations. This method is applied to the study of fine structure splitting in selected p-block and d-block elements and is further applied to the study of the open-shell heavy-element uranium(V) ion.

Epstein Barr virus (EBV)-associated smooth muscle tumors (SMT) in the central nervous system are rare tumors. EBV-associated SMT mainly occur in patient with compromised immune status. We report on a case of a HIV positive patient, who developed multiple EBV-SMTs, intracranially and in the spine. We systematically review the literature on the topic. A 46 years old female with HIV was imaged for complaints of headaches for 2 years, when an intracranial lesion was found. The patient was followed with sequential MRI scans before an excision was performed 5 years later. Pathology revealed an EBV-associated SMT. Multiple other lesions appearing in the brain and in the spine over years were treated by stereotactic radiosurgery or by surgery. At the time of this report, the patient is alive under HARRT treatment without recurrence. A systematic PRISMA guided literature research was conducted on the topic reviewing multiple databases for EBV-associated SMT located in brain or spine. We identified 52 patients from the literature and performed a pooled analysis. All patients in this cohort except one were immuno-suppressed from HIV, post-transplant therapy or because of CIS. Female predominance and a median age of 35 years was identified as was frequent multifocality. Therapeutic strategies varied but were mostly multidisciplinary with surgery. Based on our results, EBV-associated SMT should be included in the differential diagnosis of intracranial lesions mimicking meningiomas in immuno-suppressed patients. Stereotactic radiosurgery can be offered as an alternate treatment option for suitable lesions. Long-term surveillance via MRI scanning is recommended for follow up.

The utility of endocervical sampling at the time of colposcopic examination after less than high-grade screening Papanicolaou smear is unknown. To address this question, we performed a retrospective review using a colposcopy patient care database maintained at our urban academic medical center. We examined the prevalence of high-grade dysplasia in endocervical samples, the prevalence of high-grade dysplasia in directed cervical biopsies, and the correlations between high-grade endocervical dysplasia and patient factors of age and time to colposcopy. A total of 3026 patient records met inclusion criteria. Mean age at the time of colposcopy was 30 ± 9 years with a range of 21-75 years. The mean time to colposcopy was 96 ± 90 days with a range of 4-1207 days. There was no difference in mean age or days to colposcopy in women who had grade 2 or greater cervical intraepithelial neoplasia on endocervical sampling compared to those who did not. The overall prevalence of high-grade dysplasia in endocervical samples in women with less than high-grade screening Pap results was 5.3%. For all entries, 4.2% (126/3026) had grade 2 or greater cervical intraepithelial neoplasia on endocervical sampling that would not otherwise have been identified. This study demonstrates that endocervical sampling has diagnostic utility in the setting of less than high-grade referral Pap smears. No benefit was demonstrated in patients with normal cytology and high-risk strains of human papillomavirus identified on referral Pap.

Golf is a sport played around the globe, with an estimated 42.6 million people playing within the United Kingdom and United States of America alone. To date, there is limited data on the energy expenditure of golf. The present study assessed the activity energy expenditure (AEE) of 16 high-standard (handicap under 5) golfers who completed three rounds of competitive golf either carrying the golf bag (BC), using a manual push trolley (MT) or an electric trolley (ET) (Stewart Golf, Gloucester, UK). Prior to each round, participants were fitted with an Actiheart® accelerometer (Camntech, Fenstanton, UK) to estimate AEE, whilst ratings of perceived exertion (RPE) and enjoyment were collected following each round. Data were analysed using a one-way repeated measures ANOVA, with Hedges

Keplerian-Stacker is an algorithm able to combine multiple observations acquired at different epochs taking into account the orbital motion of a potential planet present in the images to boost the ultimate detection limit. In 2019, a total of 100 hours of observation were allocated to VLT VISIR-NEAR, a collaboration between ESO and Breakthrough Initiatives, to search for low mass planets in the habitable zone of the Alpha Cen AB binary system. A weak signal (S/N = 3) was reported around Alpha Cen A, at a separation of 1.1 a.u. which corresponds to the habitable zone. We have re-analysed the NEAR data using K-Stacker. This algorithm is a brute-force method able to find planets in time series of observations and to constrain their orbital parameters, even if they remain undetected in a single epoch. We scanned a total of about 3.5e+5 independent orbits, among which about 15 % correspond to fast moving orbits on which planets cannot be detected without taking into account the orbital motion. We find only a single planet candidate, which matches the C1 detection reported in Wagner et al. 2021. Despite the significant amount of time spent on this target, the orbit of this candidate remains poorly constrained due to these observations being closely distributed in 34 days. We argue that future single-target deep surveys would benefit from a K-Stacker based strategy, where the observations would be split over a significant part of the expected orbital period to better constrain the orbital parameters. This application of K-Stacker on high contrast imaging data in the mid-infrared demonstrates the capability of this algorithm to aid in the search for Earth-like planets in the habitable zone of the nearest stars with future instruments of the E-ELT such as METIS., 9 pages, 11 figures, K-Stacker github link

The term “food first” has been widely accepted as the preferred strategy within sport nutrition, although there is no agreed definition of this and often limited consideration of the implications. We propose that food first should mean “where practically possible, nutrient provision should come from whole foods and drinks rather than from isolated food components or dietary supplements.” There are many reasons to commend a food first strategy, including the risk of supplement contamination resulting in anti-doping violations. However, a few supplements can enhance health and/or performance, and therefore a food only approach could be inappropriate. We propose six reasons why a food only approach may not always be optimal for athletes: (a) some nutrients are difficult to obtain in sufficient quantities in the diet, or may require excessive energy intake and/or consumption of other nutrients; (b) some nutrients are abundant only in foods athletes do not eat/like; (c) the nutrient content of some foods with established ergogenic benefits is highly variable; (d) concentrated doses of some nutrients are required to correct deficiencies and/or promote immune tolerance; (e) some foods may be difficult to consume immediately before, during or immediately after exercise; and (f) tested supplements could help where there are concerns about food hygiene or contamination. In these situations, it is acceptable for the athlete to consider sports supplements providing that a comprehensive risk minimization strategy is implemented. As a consequence, it is important to stress that the correct terminology should be “food first but not always food only.”

Correction to: Nature Communications https://doi.org/10.1038/s41467-021-21176-6, published online 10 February 2021.The original version of this Article contained an error in Fig. 1b, in which the units incorrectly read ‘AU,’ instead of the correct ‘au’. This has been corrected in both the PDF and HTML versions of the Article.

Use of functional neuroimaging capabilities such as fMRI, DTI, MRP, MRS, AS-PET-CT, SPECT, and TMS as noninvasive tools to visualize intrinsic brain and spine morphology in relation to function have developed over the past 30 years. Amongst these imaging modalities, functional magnetic resonance imaging (fMRI) is of particular interest since it follows the physiological coupling between neuronal electrical activity and metabolic structural (cellular) activity as it relates to tissue vascularity and perfusion states. This structure–function synesis (from the Greek noun, σύνεσις = being together), leads to three effects that contribute to the fMRI signal: an increase in the blood flow velocity, a change in the mean blood volume, and most importantly, alterations in the blood oxygenation level. The latter effect has lent to the development of blood-oxygenation-level-dependent or BOLD fMRI, which has been used in establishing the topographic relationship between eloquent cortex and neurosurgical planning. As an adjunct to this modality, MRI-based diffusion tensor imaging (DTI) allows further detailed radiographic assessment of fiber tracts in the brain in relationship to the surgical lesion of interest. Herein we review the roles of fMRI and DTI for presurgical mapping to allow for maximal safe resection procedures in neurosurgery with case-based illustrations.

Looking at bivariate copulas from the perspective of conditional distributions and considering weak convergence of almost all conditional distributions yields the notion of weak conditional convergence. At first glance, this notion of convergence for copulas might seem far too restrictive to be of any practical importance - in fact, given samples of a copula $C$ the corresponding empirical copulas do not converge weakly conditional to $C$ with probability one in general. Within the class of Archimedean copulas and the class of Extreme Value copulas, however, standard pointwise convergence and weak conditional convergence can even be proved to be equivalent. Moreover, it can be shown that every copula $C$ is the weak conditional limit of a sequence of checkerboard copulas. After proving these three main results and pointing out some consequences we sketch some implications for two recently introduced dependence measures and for the nonparametric estimation of Archimedean and Extreme Value copulas., Comment: 23 pages, 9 figures

Snellen, I.A.G. et al., In this White Paper, which was submitted in response to the European Space Agency (ESA) Voyage 2050 Call, we recommend the ESA plays a proactive role in developing a global collaborative effort to construct a large high-contrast imaging space telescope, e.g. as currently under study by NASA. Such a mission will be needed to characterize a sizable sample of temperate Earth-like planets in the habitable zones of nearby Sun-like stars and to search for extraterrestrial biological activity. We provide an overview of relevant European expertise, and advocate ESA to start a technology development program towards detecting life outside the Solar System., I.S. acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No 694513. A.L.M. acknowledges the financial support of the F.R.S.-FNRS through a postdoctoral researcher grant. MB acknowledges support from the UK Science and Technology Facilities Council (STFC) research grant ST/S000631/1. I.R. acknowledges support from the Spanish Ministry of Science and Innovation and the European Regional Development Fund through grant PGC2018-098153-B-C33, as well as the support of the Generalitat de Catalunya/CERCA programme. E.P. acknowledges support from the Spanish Ministry of Science through grant PGC2018-098153-B-C31. J.M.D. acknowledges funding from the European Research Council (ERC) under the European Unions Horizon 2020 research and innovation programme (grant agreement no. 679633; Exo-Atmos) Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. We acknowledge financial support from the ASI-INAF agreement n.2018-16-HH.0 We acknowledge financial support from Spanish MCIU SEV-2017-0709 and PID2019-110689RB-I00 awards. We acknowledge financial support from the ASI-INAF agreement n.2018-16-HH.0 AV acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 757561). KH acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 771620). NJM acknowledges funding from the Leverhulme Trust, and a Science and Technology Facilities Council Consolidated Grant (ST/R000395/1). PdV acknowledges funding from the Netherlands Organisation for Scientific Research NWO (Veni Grant No. 639.041.750). IP acknowledges financial support from the ASI-INAF agreements 2019-29-HH.06-HH.0 and 2015-019-R.1-2018. FS acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 678194; FALCONER). MJ acknowledges support from the Knut and Alice Wallenberg foundation (KAW). JLB acknowledges funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No 805445. T.H. acknowledges support from the European Research Council under the Horizon 2020 Framework Program via the ERC Advanced Grant Origins 83 24 28. JLG acknowledges ISSI Team 464 for useful discussion.

Cannabis is widely used for both recreational and medicinal purposes on a global scale. There is accumulating interest in the use of cannabis and its constituents for athletic recovery, and in some instances, performance. Amidst speculation of potential beneficial applications, the effects of cannabis and its two most abundant constituents, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), remain largely un-investigated. The purpose of this review is to critically evaluate the literature describing the effects of whole cannabis, THC, and CBD, on athletic performance and recovery. While investigations of whole cannabis and THC have generally shown either null or detrimental effects on exercise performance in strength and aerobic-type activities, studies of sufficient rigor and validity to conclusively declare ergogenic or ergolytic potential in athletes are lacking. The ability of cannabis and THC to perturb cardiovascular homeostasis warrants further investigation regarding mechanisms by which performance may be affected across different exercise modalities and energetic demands. In contrast to cannabis and THC, CBD has largely been scrutinized for its potential to aid in recovery. The beneficial effects of CBD on sleep quality, pain, and mild traumatic brain injury may be of particular interest to certain athletes. However, research in each of these respective areas has yet to be thoroughly investigated in athletic populations. Elucidating the effects of whole cannabis, THC, and CBD is pertinent for both researchers and practitioners given the widespread use of these products, and their potential to interact with athletes’ performance and recovery.

Feasibility, safety, and utility of brain MRI for patients with non-MRI-conditioned cardiac implantable electrical devices (CIEDs) remains controversial. While a growing number of studies have shown safe employment in select patients under strict protocols, there is an increasing clinical need for further off-label investigations. To assess the feasibility and utility of brain MRI in neurological and neurosurgical patients with non-MRI-conditioned CIEDs using off-label protocol. We retrospectively evaluated 126 patients with non-MRI-conditioned CIEDs referred to our hospital between 2014 to 2018 for MRI under an IRB-approved protocol. A total of 126 off-label brain MRI scans were performed. The mean age was 67.5 ± 13.0. Seventy percent of scans were performed on female patients. Indications for MRI are neurosurgical (45.2%), neurological (51.6%), and others (3.2%). MRI utilization for tumor cases was highest for tumor cases (68.3%), but employment was valuable for vascular (12.7%), deep brain stimulators (3.2%), and other cases (15.9%). In the tumor category, (37.2%) of the scans were performed for initial diagnosis and pre-surgical planning, (47.7%) for post-intervention evaluation/surveillance, (15.1%) for stereotactic radiosurgery treatment (CyberKnife). No clinical complications were encountered. No functional device complications of the CIED were identified during and after the MRI in 96.9% of the studies. A 49.6% of the off-label brain MRI scans performed led to a clinically significant decision and/or intervention for the patients. A 42.9% of obtained MRI studies did not change the plan of care. A 7.9% of post-scan decision-making data was not available. We demonstrate that off-label brain MRI scans performed on select patients under a strict protocol is feasible, safe, and relevant. Almost 50% of scans provided critical information resulting in clinical intervention of the patients.