Static and Dynamic Portfolio Methods for Optimal Planning: An Empirical Analysis

Combining the complementary strengths of several algorithms through portfolio approaches has been demonstrated to be effective in solving a wide range of AI problems. Notably, portfolio techniques have been prominently applied to suboptimal (satisficing) AI planning. Here, we consider the construction of sequential planner portfolios for domainindependent optimal planning. Specifically, we introduce four techniques (three of which are dynamic) for per-instance planner schedule generation using problem instance features, and investigate the usefulness of a range of static and dynamic techniques for combining planners. Our extensive empirical analysis demonstrates the benefits of using static and dynamic sequential portfolios for optimal planning, and provides insights on the most suitable conditions for their fruitful exploitation

Exploiting Macro-actions and Predicting Plan Length in Planning as Satisfiability

The use of automatically learned knowledge for a planning domain can significantly improve the performance of a generic planner when solving a problem in this domain. In this work, we focus on the well-known SAT-based approach to planning and investigate two types of learned knowledge that have not been studied in this planning framework before: macro-actions and planning horizon. Macro-actions are sequences of actions that typically occur in the solution plans, while a planning horizon of a problem is the length of a (possibly optimal) plan solving it. We propose a method that uses a machine learning tool for building a predictive model of the optimal planning horizon, and variants of the well-known planner SatPlan and solver MiniSat that can exploit macro actions and learned planning horizons to improve their performance. An experimental analysis illustrates the effectiveness of the proposed techniques

Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients

Background: Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. Methods: This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible. We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography–mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. Results: HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. Conclusions: CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification

Extending Qualitative Spatial Theories with Emergent Spatial Concepts: An Automated Reasoning Approach

Qualitative Spatial Reasoning is an exciting research field of the Knowledge Representation and Reasoning paradigm whose application often requires the extension, refinement or combination of existent theories (as well as the associated calculus). This paper addresses the issue of the sound spatial interpretation of formal extensions of such theories; particularly the interpretation of the extension and the desired representational features. The paper shows how to interpret certain kinds of extensions of Region Connection Calculus (RCC) theory. We also show how to rebuild the qualitative calculus of these extensions.Junta de Andalucía TIC-606

Robotic ubiquitous cognitive ecology for smart homes

Robotic ecologies are networks of heterogeneous robotic devices pervasively embedded in everyday environments, where they cooperate to perform complex tasks. While their potential makes them increasingly popular, one fundamental problem is how to make them both autonomous and adaptive, so as to reduce the amount of preparation, pre-programming and human supervision that they require in real world applications. The project RUBICON develops learning solutions which yield cheaper, adaptive and efficient coordination of robotic ecologies. The approach we pursue builds upon a unique combination of methods from cognitive robotics, machine learning, planning and agent- based control, and wireless sensor networks. This paper illustrates the innovations advanced by RUBICON in each of these fronts before describing how the resulting techniques have been integrated and applied to a smart home scenario. The resulting system is able to provide useful services and pro-actively assist the users in their activities. RUBICON learns through an incremental and progressive approach driven by the feed- back received from its own activities and from the user, while also self-organizing the manner in which it uses available sensors, actuators and other functional components in the process. This paper summarises some of the lessons learned by adopting such an approach and outlines promising directions for future work

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR &lt;0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted &lt;4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (&lt;10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR&gt;6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS &lt;50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR&lt;0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

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Abstract:&nbsp; Studies show that patients with type 2 diabetes (DM2) have a higher risk of developing some type of cancer. Objective:&nbsp;to analyze the incidence and association between DM2 and cancer in patients from the “San Ricardo Pampuri” health center in Villa Carlos Paz. A retrospective observational study was carried out analyzing the medical records of 42,948 patients (years 2000-2018), 17,109 (39.8%) had DM2 and 332 had cancer (186M and 146H). The data analyzed were age, sex, type of cancer and suffering from DM2. Incidence ratios between sexes (RS = incidence in Men / incidence in Women) were calculated for some types of cancer. The work has ethical approval and corresponding confidentiality. Data were statistically analyzed with Infostat. Average age was 72 (DS 11) years for men and 68.5 (DS 12) for women (56% of the patients). 162 patients who developed cancer had DM2 (93M and 69H). In women with DM2 the incidences were: breast (51.6%), endometrium (7.5%), colon, pancreas and cervix (all with 6.5%). In women without DM2: breast (41.1%), colon (14.4%), cervix (7.8%), ovary and thyroid (both with 5.6%). In men with DM2 the incidences: prostate (27.9%), colon (19.1%), pancreas (8.8%), kidney (7.4%), Non-Hodgkin\u27s Lymphoma and bladder (both with 5.9 %). In those without DM2 they were: prostate (40%), colon (18.8%), bladder (12.5%) and melanoma (5%). The highest incidence rates between sexes (SR) for patients with DM2 were: lung (4.1), colon (3), Non-Hodgkin\u27s Lymphoma (2.7), kidney (2.3) and myeloma (2); in patients without DM2 they were bladder (3.8) and leukemia (2.3). It was observed that diabetic patients have a higher risk for pancreatic cancer (OR = 6.96; p = 0.01) and kidney (OR = 4.96; p = 0.01). Men showed a slightly increased risk for: colon (OR = 0.49; p = 0.02), bladder (OR = 0.16; p = 0.05) and kidney (OR = 0.29; p = 0 , 05). It was observed that patients without DM2 showed a slightly elevated risk for bladder cancer (OR = 0.33; p = 0.05) and melanoma (OR = 0.13; p = 0.05). Conclusions: Positive correlations were observed between cancer and age, for some tumors it could also be established with sex and DM2. Patients with DM2 showed an increased risk for pancreatic and kidney cancer and a small decrease in risk for bladder and melanoma.Resumen:&nbsp; Numerosos estudios demuestran que pacientes con diabetes tipo 2 (DM2) tienen mayor riesgo de desarrollar algún tipo&nbsp;de cáncer. Objetivo del estudio:&nbsp;analizar la incidencia y asociación entre DM2 y cáncer en pacientes del centro de salud “San Ricardo Pampuri” de Villa Carlos Paz.&nbsp; Se realizó un estudio observacional retrospectivo analizando historias clínicas de 42948 pacientes &nbsp;(años 2000-2018), 17109 (39,8%) padecían DM2 y 332 &nbsp;presentaron &nbsp;cáncer (186M y 146H). Los datos analizados fueron edad, sexo, tipo de cáncer y padecer DM2. Se calcularon ratios de incidencia entre sexos (RS=incidencia Hombres/incidencia Mujeres) para algunos tipos de cáncer.&nbsp; El trabajo cuenta con&nbsp; aprobación ética y confidencialidad correspondiente. Se analizaron los datos estadísticamente con Infostat. Edad promedio fue 72(DS 11)&nbsp;años hombres y 68,5 (DS 12) mujeres (56% de los pacientes). 162 pacientes que desarrollaron cáncer tenían DM2 (93M y 69H). En mujeres con DM2&nbsp; incidencias fueron: mama (51,6%), endometrio (7,5%), colon, páncreas y cuello de útero (todos con 6,5%). En mujeres sin DM2: mama (41,1%), colon (14,4%), cuello de útero (7,8%) ovario y tiroides (ambos con 5,6%). En hombres con DM2 las incidencias: próstata (27,9%), colon (19,1%), páncreas (8,8%), riñón (7,4%), Linfoma No Hodgkin y vejiga (ambos con 5,9%). En aquellos sin DM2 fueron: próstata (40%), colon (18,8%), vejiga (12,5%) y melanoma (5%). Las ratios de incidencia entre sexos (RS) más altos para pacientes con DM2 fueron: pulmón (4,1), colon (3), Linfoma No Hodgkin (2,7), riñón (2,3) y mieloma (2); en pacientes sin DM2 fueron vejiga (3,8) y leucemia (2,3). Se observó que pacientes diabéticos tienen un riesgo mayor para cáncer de páncreas (OR=6,96; p=0,01) y riñón (OR=4,96; p=0,01). Los hombres mostraron un riesgo levemente aumentado para: colon (OR=0,49; p=0,02), vejiga (OR=0,16; p=0,05) y riñón (OR=0,29; p=0,05). Se observó que pacientes sin DM2 mostraron un riesgo ligeramente elevado para cáncer de vejiga (OR=0,33; p=0,05) y melanoma (OR=0,13; p=0,05).&nbsp; Conclusiones:&nbsp; Se observaron correlaciones positivas entre cáncer y edad, para algunos tumores también se pudieron establecer con sexo y DM2.&nbsp; Los pacientes con DM2 mostraron un riesgo mayor para cáncer de páncreas y riñón y una pequeña disminución del riesgo para vejiga y melanoma.

Bipolar disorder integrative staging: incorporating biomarkers into progression across stages (BOARDING-PASS) – rationale and design

Bipolar disorder (BD) is a lifelong, recurrent condition with growing evidence supporting a neuroprogressive course, entailing the need to adopt staging models to guide stage-specific interventions. Although different approaches have been proposed, their application remains limited and largely based on clinical features. BOARDING-PASS is an Italian government-funded, multicenter, prospective, and observational study aimed at advancing current knowledge of BD progression through the integration of clinical, biological, neuroimaging data, alongside machine learning (ML) methodologies. The study enrolled 97 subjects (age 18–70 years), classified according to the Kupka & Hillegers’ staging model, and recruited from three secondary-level psychiatric services in Italy. The primary outcome is the longitudinal assessment of clinical stage progression over an 18-month period, with evaluations conducted at baseline (T0), T1 (6 months), T2 (12 months), and T3 (18 months after baseline). At each time point, clinical variables will be collected, as well as clinical stages assigned. Additionally, at T0, T2, and T3, peripheral blood and unstimulated saliva samples will be collected to assess epigenetic regulation of gene expression - including DNA methylation, histone modifications, and exosomal miRNAs - with a focus on key biomarkers such as C-reactive protein, proinflammatory cytokines, and BDNF, as well as microbial signatures of major oral bacterial phyla. Structural and resting-state functional MRI scans will also be acquired at the same time points: structural data will be used to compute the structural connectome based on gyrification-based covariance networks, while resting-state data will be used to assess functional connectome alterations via graph theory metrics. Finally, all multimodal data will be integrated within a supervised ML algorithm based on Support Vector Machine, with the goal of developing a refined, data-driven staging model for BD. BOARDING PASS project aligns with the growing need for a standardized, biologically informed staging framework that integrates clinical, inflammatory, epigenetic, and neuroimaging profiles to enhance prognostic accuracy and support tailored therapeutic interventions in BD

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Abstract:&nbsp; Type 2 diabetes (DBT2) affects the central nervous system (CNS) and vision. Environmental enrichment (EA), allows to develop greater physical activity and neurocognitive stimulation, being able to help in experimental animals in the treatment of CNS pathologies.&nbsp;Objective: To study the effect of exposure to EA&nbsp;on the ultrastructure of the optic nerve and metabolic markers in diabetic animals. We used 24 12-month-old male Wistar rats, divided into 6 groups, 4 with a diet with 30% saturated fat (HFD) and / or moderate consumption (0.42 g / kg weight / day) of alcohol (Alc). The 2 non-diabetic control groups (C), consumed a standard chow diet. The EA groups were housed in large cages, with treadmills and ramps, the other groups in standard animal cages. The trial lasted 16 months. Metabolic markers (lipidemia, glycemia and weight) were measured. At the end of the test, the optic nerves were extracted, fixed and processed for electron microscopy. The data obtained were analyzed by ANOVA, p≤0.05. The animals presented DBT2 at 7 months of the test, in groups HFD, Alc, HFD + Alc, hypertriglyceridemia and hypercholesterolemia and obesity were observed. Animals with EA at the end of the trial decreased their glycemic values ​​(118 ± 5 mg / dl) and had a normal weight. In the optic nerves, signs of atrophy, alteration of the shape of mitochondria and their crests were observed in the animals on the HFD and / or Alcohol diet, compared with the control groups (C and C + AE). The HFD, Alc, HFD + Alc and HFD + Alc + AE groups showed thickening of the myelin sheaths (between 39 and 233%, p = 0.01). In the animals with the HFD diet, more intracytoplasmic electrodense deposits were found, in HFD + Alc and HFD + Alc + AE the myelin sheath was observed with a greater separation of the axon (75 and 50% more, p = 0.05) than in the group C. In the Alc group, larger mitochondria were observed (119 vs 107 nm, p = 0.05) than in C. Diet and lack of physical activity led the animals to develop DBT2. This condition affected the ultrastructure of the optic nerve. Exposure to an enriched environment partially improved metabolic and ultrastructural alterations.Resumen:&nbsp; La diabetes tipo 2 (DBT2) afecta el sistema nervioso central (SNC) y la visión. El enriquecimiento ambiental (AE), permite desarrollar mayor actividad física y estímulo neurocognitivo, pudiendo ayudar en animales experimentales en el tratamiento de patologías del SNC.&nbsp;Objetivo: Estudiar el efecto de la exposición a un AE sobre la ultraestructura del nervio óptico y marcadores metabólicos en animales diabéticos. Utilizamos 24 ratas Wistar macho de 12 meses, divididas en 6 grupos, 4 con una dieta con 30% de grasas saturadas (HFD) y/o consumo moderado (0,42 g/kg peso/día) de alcohol (Alc). Los 2 grupos controles no diabéticos (C), consumieron una dieta chow estándar. Los grupos con AE se alojaron en&nbsp;jaulas grandes, con ruedas de correr y rampas, los otros grupos en jaulas estándar de bioterio.&nbsp;El ensayo duró 16 meses. Se midieron marcadores metabólicos (lipidemia, glucemia y peso). Al finalizar el ensayo los nervios ópticos fueron extraídos, fijados y procesados para microscopía electrónica. Los datos obtenidos se analizaron mediante ANOVA, p≤0,05. Los animales presentaron DBT2 a los 7 meses del ensayo, en grupos HFD, Alc, HFD+Alc se observó hipertrigliceridemia e hipercolesterolemia y obesidad. Los animales con AE al final del ensayo disminuyeron sus valores glucémicos (118 ±5 mg/dl) y tuvieron un peso normal. &nbsp;En los nervios ópticos se observaron signos de atrofia, alteración de la forma de mitocondrias y sus crestas en los animales con dieta HFD y/o Alcohol, comparados con los grupos control (C y C+AE). Los grupos HFD, Alc, HFD+Alc y HFD+Alc+AE mostraron engrosamientos de las vainas de mielina (entre 39 y 233%, p=0.01). En los animales con dieta HFD se hallaron más depósitos electrodensos intracitoplasmáticos, en HFD+Alc y HFD+Alc+AE la vaina de mielina se observó con una mayor separación del axón (75 y 50% más,&nbsp;p=0.05) que en el grupo C. En el grupo Alc se observaron mitocondrias de mayor tamaño (119 vs 107 nm,&nbsp;p=0.05) que en C.&nbsp; La dieta y falta de actividad física llevaron a los animales a desarrollar DBT2. Esta condición afectó la ultraestructura del nervio óptico. La exposición a un ambiente enriquecido logró mejorar parcialmente las alteraciones metabólicas y ultraestructurales.