Constraints on anharmonic corrections of Fuzzy Dark Matter

The cold dark matter (CDM) scenario has proved successful in cosmology. However, we lack a fundamental understanding of its microscopic nature. Moreover, the apparent disagreement between CDM predictions and subgalactic-structure observations has prompted the debate about its behaviour at small scales. These problems could be alleviated if the dark matter is composed of ultralight fields $m \sim 10^{-22}\ \text{eV}$, usually known as fuzzy dark matter (FDM). Some specific models, with axion-like potentials, have been thoroughly studied and are collectively referred to as ultralight axions (ULAs) or axion-like particles (ALPs). In this work we consider anharmonic corrections to the mass term coming from a repulsive quartic self-interaction. Whenever this anharmonic term dominates, the field behaves as radiation instead of cold matter, modifying the time of matter-radiation equality. Additionally, even for high masses, i.e. masses that reproduce the cold matter behaviour, the presence of anharmonic terms introduce a cut-off in the matter power spectrum through its contribution to the sound speed. We analyze the model and derive constraints using a modified version of CLASS and comparing with CMB and large-scale structure data.Comment: 14 pages, 7 figure

Residual enzymatic activity as a prognostic factor in patients with Gaucher disease type 1: Correlation with Zimran and GAUSS-I index and the severity of bone disease

Background: Gaucher disease (GD) is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene (GBA), causing storage of glucosylceramide in reticuloendothelial cells in multiple organs. Traditionally, the prediction of the phenotype based on the genotype has been reported to be limited.Subjects and Methods: We investigated the correlation between the enzymatic residual activity (ERA) and the phenotype at diagnosis of the disease in 45 GD Spanish patients (44 with type I and 1 with type III GD). The genotype involved two of the following previously expressed proteins: c.517A¿>¿C (T134P), 1%; c.721G¿>¿A (G202R), 17%; c.1090G¿>¿T (G325W), 13.9%; c.1208G¿>¿A (S364N), 4.1%; c.1226A¿>¿G (N370S), 17.8%; c.1246G¿>¿A (G377S), 17.6%; c.1289C¿>¿T (P391L), 8.5%; c.1448T¿>¿C (L444P), 3%; and c.1504C¿>¿T (R463C), 24.5%. Recombinant alleles, deletion of 55¿bp in exon 9 and 84GG mutation were considered as mutations with no residual enzymatic activity.Results: The ERA showed a statistically significant correlation with chitotriosidase (P¿<¿0.001), age (P¿<¿0.001), spleen size (P¿<¿0.001), ‘Zimran’s Severity Score Index’ (P¿<¿0.01) and the ‘Gaucher Disease Severity Score Index—Type I’ (P¿<¿ 0.0001) at diagnosis of the disorder. Previous to any medical intervention, a comparison between the ERA and bone involvement, demonstrated a statistically significant relationship (P¿<¿0.01) between the two variables.Conclusions: This study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis, called Protein Severity Index, which expresses the theoretical severity of the genotype presented by patients, according to the corresponding ERA

Buffered Steiner Trees for difficult instances

Buffer insertion has become an increasingly critical optimization in high performance design. The problem of finding a delay-optimal buffered Steiner tree has been an active area of research, and excellent solutions exist for most instances. However, current approaches fail to adequately solve a particular class of real-world &quot;difficult&quot; instances which are characterized by a large number of sinks, variations in sink criticalities, and varying polarity requirements. We propose a new Steiner tree construction called C-Tree for these instance types. When combined with van Ginneken style buffer insertion, C-Tree achieves higher quality solutions with fewer resources compared to traditional approaches

Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology

To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar

Air pollution and mortality in the Canary Islands: a time-series analysis

<p>Abstract</p> <p>Background</p> <p>The island factor of the cities of Las Palmas de Gran Canaria and Santa Cruz de Tenerife, along with their proximity to Africa and their meteorology, create a particular setting that influences the air quality of these cities and provides researchers an opportunity to analyze the acute effects of air-pollutants on daily mortality.</p> <p>Methods</p> <p>From 2000 to 2004, the relationship between daily changes in PM₁₀, PM_2.5, SO₂, NO₂, CO, and ozone levels and daily total mortality and mortality due to respiratory and heart diseases were assessed using Generalized Additive Poisson models controlled for potential confounders. The lag effect (up to five days) as well as the concurrent and previous day averages and distributed lag models were all estimated. Single and two pollutant models were also constructed.</p> <p>Results</p> <p>Daily levels of PM₁₀, PM_2.5, NO₂, and SO₂were found to be associated with an increase in respiratory mortality in Santa Cruz de Tenerife and with increased heart disease mortality in Las Palmas de Gran Canaria, thus indicating an association between daily ozone levels and mortality from heart diseases. The effects spread over five successive days. SO₂was the only air pollutant significantly related with total mortality (lag 0).</p> <p>Conclusions</p> <p>There is a short-term association between current exposure levels to air pollution and mortality (total as well as that due specifically to heart and respiratory diseases) in both cities. Risk coefficients were higher for respiratory and cardiovascular mortality, showing a delayed effect over several days.</p

Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.This work was supported by grants FIS-PI15/00513, FIS-PI18/00572 and RD16/0015/0001 from the Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación, Spain and FEDER: "Una manera de hacer Europa"

Desert dust outbreak in the Canary Islands (February 2020): assessment and impacts

World Weather Research Programme (WWRP 2021–1

Recommendations for ophthalmologic practice during the easing of COVID-19 control measures

In the context of the COVID-19 pandemic, this paper provides recommendations for medical eye care during the easing of control measures after lockdown. The guidelines presented are based on a literature review and consensus among all Spanish Ophthalmology Societies regarding protection measures recommended for the ophthalmologic care of patients with or without confirmed COVID-19 in outpatient, inpatient, emergency and surgery settings. We recommend that all measures be adapted to the circumstances and availability of personal protective equipment at each centre and also highlight the need to periodically update recommendations as we may need to readopt more restrictive measures depending on the local epidemiology of the virus. These guidelines are designed to avoid the transmission of SARS-CoV-2 among both patients and healthcare staff as we gradually return to normal medical practice, to prevent postoperative complications and try to reduce possible deficiencies in the diagnosis, treatment and follow-up of the ophthalmic diseases. With this update (5th) the Spanish Society of Ophthalmology is placed as one of the major ophthalmology societies providing periodic and systematized recommendations for ophthalmic care during the COVID-19 pandemic