Patient advice regarding participation in sport in children with disorders of cerebrospinal fluid (CSF) circulation: a national survey of British paediatric neurosurgeons

Background Management of children with disorders of cerebrospinal fluid (CSF) circulation is a common aspect of paediatric neurosurgical practice. Sport and physical activity play an integral role in the lives of patients in this age group. However, there is little evidence to support the dissemination of appropriate advice to children regarding such activities. The aim of this study was to evaluate the perspectives of clinicians across the UK regarding the participation of children with disorders of CSF circulation in sports. Methods Questionnaires were distributed to Consultant Paediatric Neurosurgeons practising across the UK via the Society of British Neurological Surgeons (SBNS). Five different patient scenarios were supplied, and participants were asked to choose whether they would advise participation in the following sports: Taekwondo, rugby, skiing, and football. Results An overall response rate of 66.7% (36 out of 54 paediatric neurosurgeons) was achieved. The following percentages of clinicians advocated football, rugby, Taekwondo, and skiing across all scenarios: 96%, 75%, 77%, and 97%, respectively. The majority of responders (91.2%) relied on personal experience when providing advice, whilst 50% used available literature and 19.4% used available guidelines. Conclusions There is a paucity of evidence in the literature to support the dissemination of appropriate advice to children with disorders of CSF circulation regarding participation in sports. Our findings demonstrate that the majority of clinicians rely on personal experience to make such decisions, emphasizing the necessity of larger scale studies to inform evidence-based guidelines

Failures in Reflective Functioning and Reported Symptoms of Anxiety and Depression in Bereaved Individuals: A Study on a Sample of Family Caregivers of Palliative Care Patients

Introduction. This study aims at examining the role of failures in reflective functioning in predicting anxiety and depression among family caregivers of palliative care patients deceased for at least one year. Methods. A sample of 157 bereaved participants (77.1% females, mean age = 43.50 ± 14.04 years) completed the Hospital Anxiety and Depression Scale (HADS) and the Reflective Functioning Questionnaire (RFQ). Results. Results of the correlational analysis showed that anxiety was positively correlated with uncertainty about mental states, indicating one type of impairment in reflective functioning. Anxiety was also negatively correlated with the certainty about mental states. Depression was negatively correlated with certainty but not with uncertainty about mental states. The results of regression analysis indicated that gender and certainty about mental states were statistically significant predictors of anxiety, with the final model explaining 23% of the variance. The results also showed that gender, the condition of being the main caregiver, and the certainty about mental states were significant predictors of depression, with the final model predicting 14% of the variance. Conclusions. Overall, the results of this study point out that the bereaved individuals who scored low on certainty about mental states reported more symptoms of anxiety and depression. Psychological interventions to prevent mental disorders and to promote psychological health in the context of palliative care should carefully consider these findings

Clinical and neurocognitive predictors of functional outcome in depressed patients with partial response to treatment: one year follow-up study

Background: Cognitive dysfunction represents a distinct biological and clinical dimension in major depression disorders (MDD) and cognitive performance strongly affects psychosocial functioning in patients diagnosed with MDD. Objective: To assess which neurocognitive variables at baseline predict the functional outcome of MDD patients in a 1-year follow-up study as assessed by Functioning Assessment Short Test (FAST) and whether the improvement observed on affective and cognitive symptoms in our 12 week-prospective observational study after treatment with selective serotonin reuptake inhibitors (SSRIs) and selective noradrenalin reuptake inhibitors (SNRIs) can affect the following long-term psychosocial functional outcome at 1 year in the same MDD patients. Methods: We recruited a total of 31 patients (8 males; 23 females) with MDD who had previously completed a pharmacological treatment with SSRIs (n = 22) or SNRIs (n = 9) for 12 weeks, and then continued the same pharmacological treatment for 1 year. After an average 1-year follow-up, they were interviewed with the FAST to assess functional outcome. Multivariate analyses were applied to identify clinical and neurocognitive predictors of functional outcome. Results: Total Montreal Cognitive Assessment (MoCA), Digit Span forward (Span F) and backward (Span B), and 15 Rey words immediate recall (Rey I) scores significantly correlated with FAST. However, after performing regression models only Rey immediate recall score was useful to predict long-term functional outcome (Pearson correlation coefficient R= -0.68, p < 0.001) in four specific subdomains of FAST. When considering changes in affective and cognitive symptoms at the end of the 12 weeks of pharmacological treatment with SSRI or SNRIs (T1-T0) by multiple regression analysis, we found that Span F-test predicted scores in the FAST leisure domain, whereas, changes in Span F, Frontal Assessment Battery (FAB) and Rey I predicted psychosocial functioning in the specific 'cognitive' subdomains of FAST. Conclusion: Our data suggest that long-term psychosocial functioning can be influenced by neurocognitive performance at baseline, with verbal memory playing a key role in overall functioning. Furthermore, improvement in verbal memory can predict functional outcome at one year in MDD patients with a recent history of partial response to antidepressants

A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut. There is growing evidence in Crohn’s disease (CD) of the existence of a preclinical period characterized by immunological changes preceding symptom onset that starts years before diagnosis. Gaining insight into this preclinical phase will allow disease prediction and prevention. Analysis of preclinical serum samples, up to 6 years before IBD diagnosis (from the PREDICTS cohort), revealed the identification of a unique glycosylation signature on circulating antibodies (IgGs) characterized by lower galactosylation levels of the IgG fragment crystallizable (Fc) domain that remained stable until disease diagnosis. This specific IgG2 Fc glycan trait correlated with increased levels of antimicrobial antibodies, specifically anti-Saccharomyces cerevisiae (ASCA), pinpointing a glycome–ASCA hub detected in serum that predates by years the development of CD. Mechanistically, we demonstrated that this agalactosylated glycoform of ASCA IgG, detected in the preclinical phase, elicits a proinflammatory immune pathway through the activation and reprogramming of innate immune cells, such as dendritic cells and natural killer cells, via an FcγR-dependent mechanism, triggering NF-κB and CARD9 signaling and leading to inflammasome activation. This proinflammatory role of ASCA was demonstrated to be dependent on mannose glycan recognition and galactosylation levels in the IgG Fc domain. The pathogenic properties of (anti-mannose) ASCA IgG were validated in vivo. Adoptive transfer of antibodies to mannan (ASCA) to recipient wild-type mice resulted in increased susceptibility to intestinal inflammation that was recovered in recipient FcγR-deficient mice. Here we identify a glycosylation signature in circulating IgGs that precedes CD onset and pinpoint a specific glycome–ASCA pathway as a central player in the initiation of inflammation many years before CD diagnosis. This pathogenic glyco-hub may constitute a promising new serum biomarker for CD prediction and a potential target for disease prevention.We wish to acknowledge the Gastroenterology Department of Centro Hospitalar Universitário de Santo António, in particular P. Lago, for providing samples from individuals with established CD. We kindly thank J. Rojo from the Instituto de Investigaciones Químicas (Universidad de Sevilla) for providing us with the di-GlcNAc glycodendrimer. We would also like to acknowledge J. V. Ravetch (Rockefeller University) and M. S. Cragg (University of Southampton) for kindly providing us with the FcγR-deficient mice used in the in vivo studies. S.S.P. acknowledges funding from the US Department of Defense, US Army Medical Research Acquisition Activity and FY18Peer-Reviewed Medical Research Program Investigator-Initiated Research Award (award number W81XWH1920053). S.S.P. also acknowledges funding from the European Crohn’s and Colitis Organisation (ECCO) Pioneer Award 2021, the International Organization for the study of Inflammatory Bowel Disease (IOIBD) and the Portuguese Foundation for Science and Technology (FCT; EXPL/MED-ONC/0496/2021). J.G. acknowledges funding from European Society of Clinical Microbiology and Infectious Diseases (ESCMID ResearchGrant 2022), European Crohn’s and Colitis Organisation (ECCO Grant 2023) and FCT (2020.00088.CEECIND). C.S.R. thanks FCT forfunding (2020.08422.BD). I.A. acknowledges funding from FCT (2022.00337.CEECIND) and the BIAL Foundation and PortugueseMedical Association (Maria de Sousa Award 2023). E.L.-G. thanks FCT for funding (UI/BD/152866/2022). F.P. and Z.H.G. were partially supported by the Kenneth-Rainin Foundation (20210021). B.C. acknowledges funding from FCT(CEECINST/00123/2021/CP1772/CT0001). J.T. acknowledges funding from the Portuguese Society of Gastroenterology and from Luz Saúde (Grupo dE iNvestIgação em Patologia Digestiva LUz Saúde LH.INV.F2019015). This study was also cofunded by the EuropeanUnion (GlycanTrigger, grant agreement number 101093997). The views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. This study was conducted under support of Peer-Reviewed Medical Research Program (PR180831P1). The views expressed in this article reflect the results of the research conducted by the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, the Henry M. Jackson Foundation for the Advancement of Military Medicine or the US Government. There are no restrictions on its use. This article was prepared while R.M.L. was employed at Henry M. Jackson Foundation for the Advancement of Military Medicine. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services or the US Government. C.K.P. is an employee of the US Government. This work was prepared as part of official duties. Title 17 U.S.C. §105provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties

HADES RV Programme with HARPS-N at TNG XII. The abundance signature of M dwarf stars with planets

Most of our current knowledge on planet formation is still based on the analysis of main-sequence, solar-type stars. Conversely, detailed chemical studies of large samples of M-dwarf planet hosts are still missing. We develop for the first time a methodology to determine stellar abundances of elements others than iron for M dwarf stars from high-resolution, optical spectra. Our methodology is based on the use of principal component analysis and sparse Bayesian's methods. We made use of a set of M dwarfs orbiting around an FGK primary with known abundances to train our methods. We applied our methods to derive stellar metalliticies and abundances of a large sample of M dwarfs observed within the framework of current radial velocity surveys. We then used a sample of nearby FGK stars to cross-validate our technique by comparing the derived abundance trends in the M dwarf sample with those found on the FGK stars. The metallicity distribution of the different subsamples shows that M dwarfs hosting giant planets show a planet-metallicity correlation as well as a correlation with the stellar mass. M dwarfs hosting low-mass planets do not seem to follow the planet-metallicity correlation. We also found that the frequency of low-mass planets does not depend on the mass of the stellar host. These results seem in agreement with previous works. However, we note that for giant planet hosts our metallicities predict a weaker planet metallicity correlation but a stronger mass-dependency than photometric values. We show, for the first time, that there seems to be no differences in the abundance distribution of elements different from iron between M dwarfs with and without known planets. Our data shows that low-mass stars with planets follow the same metallicity, mass, and abundance trends than their FGK counterparts.Comment: Accepted for publication by Astronomy & Astrophysic

HADES RV Programme with HARPS-N at TNG XIII. A sub-Neptune around the M dwarf GJ 720 A

Context. The high number of super-Earth and Earth-like planets in the habitable zone (HZ) detected around M-dwarf stars in the last years has revealed these stellar objects to be the key for planetary radial velocity (RV) searches. Aims. Using the HARPS-N spectrograph within The HArps-n red Dwarf Exoplanet Survey (HADES) we reach the precision needed to detect small planets with a few Earth masses using the RV technique. Methods. We obtained 138 HARPS-N RV measurements between 2013 May and 2020 September of GJ 720 A, classified as an M0.5V star located at a distance of 15.56 pc. To characterize the stellar variability and to discern the periodic variation due to the Keplerian signals from those related to stellar activity, the HARPS-N spectroscopic activity indicators and the simultaneous photometric observations were analyzed. The combined analysis of HARPS-N RVs and activity indicators let us to address the nature of the periodic signals. The final model and the orbital planetary parameters were obtained by fitting simultaneously the stellar variability and the Keplerian signal using a Gaussian process regression and following a Bayesian criterion. Results. The HARPS-N RV periodic signals around 40 d and 100 d have counterparts at the same frequencies in HARPS-N activity indicators and photometric light curves. Then we attribute these periodicities to stellar activity the former period being likely associated with the stellar rotation. GJ 720 A shows the most significant signal at 19.466$\pm$0.005 d with no counterparts in any stellar activity indices. We hence ascribe this RV signal, having a semiamplitude of 4.72$\pm$0.27 m/s , to the presence of a sub-Neptune mass planet. The planet GJ 720 Ab has a minimum mass of 13.64$\pm$0.79 M$_{\oplus}$, it is in circular orbit at 0.119$\pm$0.002 AU from its parent star, and lies inside the inner boundary of the HZ around its parent star

Probing the Physics of the Solar Atmosphere with the Multi-slit Solar Explorer (MUSE). I. Coronal Heating

The Multi-slit Solar Explorer (MUSE) is a proposed mission composed of a multislit extreme ultraviolet (EUV) spectrograph (in three spectral bands around 171 Å, 284 Å, and 108 Å) and an EUV context imager (in two passbands around 195 Å and 304 Å). MUSE will provide unprecedented spectral and imaging diagnostics of the solar corona at high spatial (≤0.″5) and temporal resolution (down to ∼0.5 s for sit-and-stare observations), thanks to its innovative multislit design. By obtaining spectra in four bright EUV lines (Fe ix 171 Å, Fe xv 284 Å, Fe xix-Fe xxi 108 Å) covering a wide range of transition regions and coronal temperatures along 37 slits simultaneously, MUSE will, for the first time, "freeze"(at a cadence as short as 10 s) with a spectroscopic raster the evolution of the dynamic coronal plasma over a wide range of scales: from the spatial scales on which energy is released (≤0.″5) to the large-scale (∼170″ × 170″) atmospheric response. We use numerical modeling to showcase how MUSE will constrain the properties of the solar atmosphere on spatiotemporal scales (≤0.″5, ≤20 s) and the large field of view on which state-of-the-art models of the physical processes that drive coronal heating, flares, and coronal mass ejections (CMEs) make distinguishing and testable predictions. We describe the synergy between MUSE, the single-slit, high-resolution Solar-C EUVST spectrograph, and ground-based observatories (DKIST and others), and the critical role MUSE plays because of the multiscale nature of the physical processes involved. In this first paper, we focus on coronal heating mechanisms. An accompanying paper focuses on flares and CMEs

The GAPS programme at TNG: XLIII. A massive brown dwarf orbiting the active M dwarf TOI-5375

Context. Massive substellar companions orbiting active low-mass stars are rare. They, however, offer an excellent opportunity to study the main mechanisms involved in the formation and evolution of substellar objects. Aims: We aim to unravel the physical nature of the transit signal observed by the TESS space mission on the active M dwarf TOI-5375. Methods: We analysed the available TESS photometric data as well as high-resolution (R ~ 115 000) HARPS-N spectra. We combined these data to characterise the star TOI-5375 and to disentangle signals related to stellar activity from the companion transit signal in the light-curve data. We ran a Markov chain Monte Carlo analysis to derive the orbital solution and applied state-of-the-art Gaussian process regression to deal with the stellar activity signal. Results: We reveal the presence of a companion in the boundary between the brown dwarfs and the very-low-mass stars orbiting around the star TOI-5375. The best-fit model corresponds to a companion with an orbital period of 1.721564 ± 10−6 d, a mass of 77 ± 8 MJ, and a radius of 0.99 ± 0.16 RJ. Conclusions: We derive a rotation period for the host star of 1.9692 ± 0.0004 d, and we conclude that the star is very close to synchronising its rotation with the orbital period of the companion

The GAPS programme at TNG XLV. A massive brown dwarf orbiting the active M dwarf TOI-5375

Context. Massive substellar companions orbiting active low-mass stars are rare. They, however, offer an excellent opportunity to study the main mechanisms involved in the formation and evolution of substellar objects. Aims. We aim to unravel the physical nature of the transit signal observed by the TESS space mission on the active M dwarf TOI-5375. Methods. We analysed the available TESS photometric data as well as high-resolution (R $\sim$ 115000) HARPS-N spectra. We combined these data to characterise the star TOI-5375 and to disentangle signals related to stellar activity from the companion transit signal in the light-curve data. We ran an MCMC analysis to derive the orbital solution and apply state-of-the-art Gaussian process regression to deal with the stellar activity signal. Results. We reveal the presence of a companion in the brown dwarf / very-low-mass star boundary orbiting around the star TOI-5375. The best-fit model corresponds to a companion with an orbital period of 1.721564 $\pm$ 10$^{\rm -6}$ d, a mass of 77 $\pm$ 8 $M_{\rm J}$ and a radius of 0.99 $\pm$ 0.16 $R_{\rm J}$. We derive a rotation period for the host star of 1.9692 $\pm$ 0.0004 d, and we conclude that the star is very close to synchronising its rotation with the orbital period of the companion.Comment: Submitted to Astronomy & Astrophysics (under review

Antithrombotic therapy and survival in patients with malignant disease

A broad range of studies suggest a two-way relationship between cancer and venous thromboembolism (VTE). Patients with cancer have consistently been shown to be at elevated risk for VTE; this risk is partly driven by an intrinsic hypercoagulable state elicited by the tumour itself. Conversely, thromboembolic events in patients without obvious risk factors are often the first clinical manifestation of an undiagnosed malignancy. The relationship between VTE and cancer is further supported by a number of trials and meta-analyses which, when taken together, strongly suggest that antithrombotic therapy can extend survival in patients with cancer by a mechanism that extends beyond its effect in preventing VTE. Moreover, accumulating evidence from in vitro and in vivo studies has shown that tumour growth, invasion, and metastasis are governed, in part, by elements of the coagulation system. On 22 May 2009, a group of health-care providers based in the United Kingdom met in London, England, to examine recent advances in cancer-associated thrombosis and its implications for UK clinical practice. As part of the discussion, attendees evaluated evidence for and against an effect of antithrombotic therapy on survival in cancer. This paper includes a summary of the data presented at the meeting and explores potential mechanisms by which antithrombotic agents might exert antitumour effects. The summary is followed by a consensus statement developed by the group