Leptomeningeal metastasis from solid tumours: EANO–ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Central nervous system; Clinical practice guideline; NeurologicalSistema nerviós central; Guia de pràctica clínica; NeurològicSistema nervioso central; Guía de práctica clínica; NeurológicoThis Clinical Practice Guideline provides recommendations for managing leptomeningeal metastases from solid tumours

Evolution of AANAT: expansion of the gene family in the cephalochordate amphioxus

<p>Abstract</p> <p>Background</p> <p>The arylalkylamine <it>N</it>-acetyltransferase (AANAT) family is divided into structurally distinct vertebrate and non-vertebrate groups. Expression of vertebrate AANATs is limited primarily to the pineal gland and retina, where it plays a role in controlling the circadian rhythm in melatonin synthesis. Based on the role melatonin plays in biological timing, AANAT has been given the moniker "the Timezyme". Non-vertebrate AANATs, which occur in fungi and protists, are thought to play a role in detoxification and are not known to be associated with a specific tissue.</p> <p>Results</p> <p>We have found that the amphioxus genome contains seven <it>AANAT</it>s, all having non-vertebrate type features. This and the absence of <it>AANATs </it>from the genomes of Hemichordates and Urochordates support the view that a major transition in the evolution of the <it>AANATs </it>may have occurred at the onset of vertebrate evolution. Analysis of the expression pattern of the two most structurally divergent <it>AANAT</it>s in <it>Branchiostoma lanceolatum </it>(<it>bl</it>) revealed that they are expressed early in development and also in the adult at low levels throughout the body, possibly associated with the neural tube. Expression is clearly not exclusively associated with the proposed analogs of the pineal gland and retina. blAANAT activity is influenced by environmental lighting, but light/dark differences do not persist under constant light or constant dark conditions, indicating they are not circadian in nature. bfAANATα and bfAANATδ' have unusually alkaline (> 9.0) optimal pH, more than two pH units higher than that of vertebrate AANATs.</p> <p>Conclusions</p> <p>The substrate selectivity profiles of bfAANATα and δ' are relatively broad, including alkylamines, arylalkylamines and diamines, in contrast to vertebrate forms, which selectively acetylate serotonin and other arylalkylamines. Based on these features, it appears that amphioxus AANATs could play several roles, including detoxification and biogenic amine inactivation. The presence of seven AANATs in amphioxus genome supports the view that arylalkylamine and polyamine acetylation is important to the biology of this organism and that these genes evolved in response to specific pressures related to requirements for amine acetylation.</p

What factors promote student resilience on a level 1 distance learning module?

Resilience is understood to be the ability to adapt positively in the face of adversity. In relation to new students on a distance learning module, this can mean how they adapt and make sense of the demands of their chosen study to enable them to persist in their studies. This article reports a small-scale study involving semistructured telephone interviews with students on a level 1 distance learning module at the UK Open University. Students identified the challenges they experienced such as carving out time to study alongside other commitments, as well as developing their academic writing. Students also identified factors that enabled them to adapt to these challenges and be successful in continuing to study. Students rated highly the support they received from tutors in the form of tailored, detailed feedback on their assignments. Other factors that enabled students to persist in their studies were time management, self-belief and motivation

Testing the running of the cosmological constant with Type Ia Supernovae at high z

Within the Quantum Field Theory context the idea of a "cosmological constant" (CC) evolving with time looks quite natural as it just reflects the change of the vacuum energy with the typical energy of the universe. In the particular frame of Ref.[30], a "running CC" at low energies may arise from generic quantum effects near the Planck scale, M_P, provided there is a smooth decoupling of all massive particles below M_P. In this work we further develop the cosmological consequences of a "running CC" by addressing the accelerated evolution of the universe within that model. The rate of change of the CC stays slow, without fine-tuning, and is comparable to H^2 M_P^2. It can be described by a single parameter, \nu, that can be determined from already planned experiments using SNe Ia at high z. The range of allowed values for \nu follow mainly from nucleosynthesis restrictions. Present samples of SNe Ia can not yet distinguish between a "constant" CC or a "running" one. The numerical simulations presented in this work show that SNAP can probe the predicted variation of the CC either ruling out this idea or confirming the evolution hereafter expected.Comment: LaTeX, 51 pages, 13 figures, 1 table, references added, typos corrected, version accepted in JCA

The Effort of Increasing Reynolds Number in Projection-Based Reduced Order Methods: From Laminar to Turbulent Flows

We present in this double contribution two different reduced order strategies for incompressible parameterized Navier-Stokes equations characterized by varying Reynolds numbers. The first strategy deals with low Reynolds number (laminar flow) and is based on a stabilized finite element method during the offline stage followed by a Galerkin projection on reduced basis spaces generated by a greedy algorithm. The second methodology is based on a full order finite volume discretization. The latter methodology will be used for flows with moderate to high Reynolds number characterized by turbulent patterns. For the treatment of the mentioned turbulent flows at the reduced order level, a new POD-Galerkin approach is proposed. The new approach takes into consideration the contribution of the eddy viscosity also during the online stage and is based on the use of interpolation. The two methodologies are tested on classic benchmark test cases

Knowledge and attitudes of primary healthcare patients regarding population-based screening for colorectal cancer

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the extent of knowledge of primary health care (PHC) patients about colorectal cancer (CRC), their attitudes toward population-based screening for this disease and gender differences in these respects.</p> <p>Methods</p> <p>A questionnaire-based survey of PHC patients in the Balearic Islands and some districts of the metropolitan area of Barcelona was conducted. Individuals between 50 and 69 years of age with no history of CRC were interviewed at their PHC centers.</p> <p>Results</p> <p>We analyzed the results of 625 questionnaires, 58% of which were completed by women. Most patients believed that cancer diagnosis before symptom onset improved the chance of survival. More women than men knew the main symptoms of CRC. A total of 88.8% of patients reported that they would perform the fecal occult blood test (FOBT) for CRC screening if so requested by PHC doctors or nurses. If the FOBT was positive and a colonoscopy was offered, 84.9% of participants indicated that they would undergo the procedure, and no significant difference by gender was apparent. Fear of having cancer was the main reason for performance of an FOBT, and also for not performing the FOBT, especially in women. Fear of pain was the main reason for not wishing to undergo colonoscopy. Factors associated with reluctance to perform the FOBT were: <b><it>(i) </it></b>the idea that that many forms of cancer can be prevented by exercise and, <b><it>(ii) </it></b>a reluctance to undergo colonoscopy if an FOBT was positive. Factors associated with reluctance to undergo colonoscopy were: <b><it>(i) </it></b>residence in Barcelona, <b><it>(ii) </it></b>ignorance of the fact that early diagnosis of CRC is associated with better prognosis, <b><it>(iii) </it></b>no previous history of colonoscopy, and <b><it>(iv) </it></b>no intention to perform the FOBT for CRC screening.</p> <p>Conclusion</p> <p>We identified gaps in knowledge about CRC and prevention thereof in PHC patients from the Balearic Islands and the Barcelona region of Spain. If fears about CRC screening, and CRC per se, are addressed, and if it is emphasized that CRC is preventable, participation in CRC screening programs may improve.</p

GEA 3162, a peroxynitrite donor, induces Bcl-2-sensitive, p53-independent apoptosis in murine bone marrow cells

AbstractApoptosis may be regulated by oxidants such as peroxynitrite (ONOO−). The tumour suppressor, p53, has been reported to play a crucial role in apoptosis induced by oxidants, therefore we assessed the ability of a ONOO− donor, GEA 3162, to activate caspases and induce mitochondrial permeability in a p53-deficient murine bone marrow cell line, Jaws II. Furthermore, these cells were stably transfected with Bcl-2, in order to investigate the impact of this survival protein on ONOO−-induced apoptosis. GEA 3162 activated caspases and induced loss of mitochondrial membrane potential in Jaws II cells. In particular, caspases 3 and 2 were activated, alongside minor activation of caspases 8 and 9, and apoptosis was partially dependent upon p38 MAP kinase activation, with little or no role for JNK. Overexpression of Bcl-2 abolished activation of all caspases and reduced the change in mitochondrial membrane potential. Thus, we have demonstrated that the ONOO− donor, GEA 3162, induces apoptosis in Jaws II murine myeloid cells despite lacking functional p53, via a pathway that principally involves caspases 2 and 3 and mitochondrial changes. This is blocked by overexpression of Bcl-2 via a mechanism that does not appear to merely reflect stabilisation of the mitochondrial membrane

A Core Outcome Set for Efficacy of Acute Treatment of Hereditary Angioedema

BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internetbased survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9 -point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The fi rst round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of fi ve key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of fi ve key outcomes. Crown Copyright (c) 2024 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). (J Allergy Clin Immunol Pract 2024;12:1614-21

The role of the urban landscape on species with contrasting dispersal ability: insights from greening plans for Barcelona

With the expansion of urban areas, promoting urban biodiversity is now a priority. Many municipalities are implementing greening strategies to improve and increase green space within city boundaries. The effectiveness of these strategies, while rarely assessed, likely depends on the landscape and on relevant species intrinsic traits such as dispersal ability. Using a spatially explicit individual-based model, we evaluated the effect of the urban landscape on the projected distribution of three butterfly species with contrasting dispersal abilities, and assessed the effectiveness of the Barcelona greening strategy as a case study. Species distribution (in terms of patch occupancy) and effectiveness (in terms of population size and number of occupied gardens) were analysed using generalised linear models. The percentage of (semi) natural source area around each urban green space (garden hereafter) was the most important variable for the distribution of all three types of species, followed by the percentage of neighbouring gardens and by the garden carrying capacity, although the effect of neighbouring gardens was negative in the early phase of colonisation. The planned Barcelona greening strategy increased the number of gardens occupied by high and medium, but not by low dispersive species. Increasing the carrying capacity of the gardens improved colonisation for all three species types. While the best strategies can be context dependent, our results indicated that increasing garden area might be more effective in the long term but it can be overridden by garden capacity in the short term, especially if there are constraints to increasing garden area