Excavaciones en el Grau Vell

Noticias preliminares de la campaña de 1983

Efficient training of energy-based models via spin-glass control

[EN] We introduce a new family of energy-based probabilistic graphical models for efficient unsupervised learning. Its definition is motivated by the control of the spin-glass properties of the Ising model described by the weights of Boltzmann machines. We use it to learn the Bars and Stripes dataset of various sizes and the MNIST dataset, and show how they quickly achieve the performance offered by standard methods for unsupervised learning. Our results indicate that the standard initialization of Boltzmann machines with random weights equivalent to spin-glass models is an unnecessary bottleneck in the process of training. Furthermore, this new family allows for very easy access to low-energy configurations, which points to new, efficient training algorithms. The simplest variant of such algorithms approximates the negative phase of the log-likelihood gradient with no Markov chain Monte Carlo sampling costs at all, and with an accuracy sufficient to achieve good learning and generalization.ML and AA groups acknowledge the Spanish Ministry MINECO and State Research Agency AEI (FIDEUA PID2019-106901GBI00/10.13039/501100011033, Severo Ochoa Grant Nos. SEV-2015-0522 and CEX2019-000910-S, FPI), the European Social Fund, Fundacio Cellex, Fundacio Mir-Puig, Generalitat de Catalunya (AGAUR Grant Nos. 2017 SGR 1341 and SGR 1381, CERCA program, QuantumCAT U16-011424, co-funded by ERDF Operational Program of Catalonia 2014-2020), ERC AdG NOQIA and CERQUTE, EU FEDER, MINECO-EU QUANTERA MAQS (funded by the State Research Agency AEI PCI2019-111828-2/10.13039/501100011033), the National Science Centre, Poland-Symfonia Grant No. 2016/20/W/ST4/00314 and the AXA Chair in Quantum Information Science. A P-K acknowledges funding from Fundacio Obra Socialla Caixa' (LCF/BQ/ES15/10360001) and the European Union's Horizon 2020 research and innovation programme-Grant Agreement No. 648913. G M-G acknowledges funding from Fundacio Obra Social 'la Caixa' (LCF-ICFO grant). M A G-M acknowledges funding from the Spanish Ministry of Education and Vocational Training (MEFP) through the Beatriz Galindo program 2018 (BEAGAL18/00203).Pozas-Kerstjens, A.; Muñoz-Gil, G.; Piñol, E.; Garcia March, MA.; Acín, A.; Lewenstein, M.; Grzybowski, PR. (2021). Efficient training of energy-based models via spin-glass control. Machine Learning: Science and Technology. 2(2). https://doi.org/10.1088/2632-2153/abe8070250262

Universal representation by Boltzmann machines with Regularised Axons

It is widely known that Boltzmann machines are capable of representing arbitrary probability distributions over the values of their visible neurons, given enough hidden ones. However, sampling -- and thus training -- these models can be numerically hard. Recently we proposed a regularisation of the connections of Boltzmann machines, in order to control the energy landscape of the model, paving a way for efficient sampling and training. Here we formally prove that such regularised Boltzmann machines preserve the ability to represent arbitrary distributions. This is in conjunction with controlling the number of energy local minima, thus enabling easy \emph{guided} sampling and training. Furthermore, we explicitly show that regularised Boltzmann machines can store exponentially many arbitrarily correlated visible patterns with perfect retrieval, and we connect them to the Dense Associative Memory networks.Comment: 12 pages. Updated reference

A propensity-score-matched analysis of laparoscopic vs open surgery for rectal cancer in a population-based study

Aim: the oncological risk/benefit trade-off for laparoscopy in rectal cancer is controversial. Our aim was to compare laparoscopic vs open surgery for resection of rectal cancer, using unselected data from the public healthcare system of Catalonia. Methods: this was a multicentre retrospective cohort study of all patients who had surgery with curative intent for primary rectal cancer at Catalonian public hospitals from 2011 to 2012. We obtained follow-up data for up to 5 years. To minimize the differences between the two groups, we performed propensity score matching on baseline patient characteristics. We used multivariate Cox proportional hazards regression analyses to assess locoregional relapse at 2 years and death at 2 and 5 years. Results: of 1513 patients with Stage I-III rectal cancer, 933 (61.7%) had laparoscopy (conversion rate 13.2%). After applying our propensity score matching strategy (2:1), 842 laparoscopy patients were matched to 517 open surgery patients. Multivariate Cox analysis of death at 2 years [hazard ratio (HR) 0.65, 95% CI 0.48, 0.87; P = 0.004] and 5 years (HR 0.61, 95% CI 0.5, 0.75; P < 0.001) and of local relapse at 2 years (HR 0.44, 95% CI 0.27, 0.72; P = 0.001) showed laparoscopy to be an independent protective factor compared with open surgery. Cconclusions: laparoscopy results in lower locoregional relapse and long-term mortality in rectal cancer in unselected patients with all-risk groups included. Studies using long-term follow-up of cohorts and unselected data can provide information on clinically relevant outcomes to supplement randomized controlled trials

Awareness of Diagnosis in Persons with Early-Stage Alzheimer's Disease : An Observational Study in Spain

Limited information is available on people's experiences of living with Alzheimer's disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures. We conducted an observational, cross-sectional study in 21 memory clinics in Spain. Persons aged 50-90 years, diagnosed with prodromal or mild AD (NIA/AA criteria), a Mini Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5 or 1.0 were recruited. The Representations and Adjustment to Dementia Index (RADIX) was used to assess participants' beliefs about their condition and its consequences. A total of 149 persons with early-stage AD were studied. Mean (SD) age was 72.3 (7.0) years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a descriptive term related to specific AD symptoms (e.g., memory difficulties) when asked what they called their condition. Participants aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more depressive symptoms, and poorer life satisfaction and quality of life compared to those without awareness of their specific diagnosis. Practical and emotional consequences RADIX scores showed a significant negative correlation with Quality of Life in Alzheimer's Disease score (rho = − 0.389 and − 0.413, respectively; p < 0.0001). Years of education was the only predictor of awareness of AD diagnosis [OR = 1.04 (95% CI 1.00-1.08); p = 0.029]. Awareness of diagnosis was a common phenomenon in persons with early-stage AD negatively impacting their quality of life. Understanding illness representations in earlier stages may facilitate implementing optimized care that supports improved quality of life and well-being

BNIP3 Is Involved in Muscle Fiber Atrophy in Late-Onset Pompe Disease Patients

Late-onset Pompe disease (LOPD) is a rare genetic disorder produced by mutations in the GAA gene and is characterized by progressive muscle weakness. LOPD muscle biopsies show accumulation of glycogen along with the autophagic vacuoles associated with atrophic muscle fibers. The expression of molecules related to muscle fiber atrophy in muscle biopsies of LOPD patients was studied using immunofluorescence and real-time PCR. BCL2 and adenovirus E1B 19-kDa interacting protein 3 (BNIP3), a well-known atrogene, was identified as a potential mediator of muscle fiber atrophy in LOPD muscle biopsies. Vacuolated fibers in LOPD patient muscle biopsies were smaller than nonvacuolated fibers and expressed BNIP3. The current data suggested that BNIP3 expression is regulated by inhibition of the AKT-mammalian target of rapamycin pathway, leading to phosphorylation of Unc-51 like autophagy activating kinase 1 (ULK1) at Ser317 by AMP-activated protein kinase. Myoblasts and myotubes obtained from LOPD patients and age-matched controls were studied to confirm these results using different molecular techniques. Myotubes derived from LOPD patients were likewise smaller and expressed BNIP3. Conclusively, transfection of BNIP3 into control myotubes led to myotube atrophy. These findings suggest a cascade that starts with the inhibition of the AKT-mammalian target of rapamycin pathway and activation of BNIP3 expression, leading to progressive muscle fiber atrophy. These results open the door to potential new treatments targeting BNIP3 to reduce its deleterious effects on muscle fiber atrophy in Pompe disease.Peer reviewe

Mendelian Randomisation Confirms the Role of Y-Chromosome Loss in Alzheimer’s Disease Aetiopathogenesis in Men

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer’s disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10−20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.P.G.-G. (Pablo García-González) is supported by CIBERNED employment plan CNV-304-PRF-866. CIBERNED is integrated into ISCIII (Instituto de Salud Carlos III). I.d.R is supported by a national grant from the Instituto de Salud Carlos III FI20/00215. A.C. (Amanda Cano) acknowledges the support of the Spanish Ministry of Science, Innovation, and Universities under the grant Juan de la Cierva (FJC2018-036012-I). M.B. (Mercé Boada) and A.R. (Agustín Ruiz) are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240, and PI19/01301. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. Acción Estratégica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III)—Subdirección General de Evaluación—and the Fondo Europeo de Desarrollo Regional (FEDER—“Una manera de hacer Europa”). Genotyping of the ACE MCI-EADB samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW project number 733051061). This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND). Partial funding for open access charge: Universidad de Málag

Medical help-seeking intentions among patients with early Alzheimer’s disease

BackgroundLimited information is available on the active process of seeking medical help in patients with Alzheimer’s disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors.MethodsA multicenter, non-interventional study was conducted including patients of 50–90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer’s Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5–1.0. A multivariate logistic regression analysis was conducted.ResultsA total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016).ConclusionUnderstanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis