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Previous studies for cancer biomarker discovery based on pre-diagnostic blood DNA methylation (DNAm) profiles, either ignore the explicit modeling of the Time To Diagnosis (TTD), or provide inconsistent results. This lack of consistency is likely due to the limitations of standard EWAS approaches, that model the effect of DNAm at CpG sites on TTD independently. In this work, we aim to identify blood DNAm profiles associated with TTD, with the aim to improve the reliability of the results, as well as their biological meaningfulness. We argue that a global approach to estimate CpG sites effect profile should capture the complex (potentially non-linear) relationships interplaying between sites. To prove our concept, we develop a new Deep Learning-based approach assessing the relevance of individual CpG Islands (i.e., assigning a weight to each site) in determining TTD while modeling their combined effect in a survival analysis scenario. The algorithm combines a tailored sampling procedure with DNAm sites agglomeration, deep non-linear survival modeling and SHapley Additive exPlanations (SHAP) values estimation to aid robustness of the derived effects profile. The proposed approach deals with the common complexities arising from epidemiological studies, such as small sample size, noise, and low signal-to-noise ratio of blood-derived DNAm. We apply our approach to a prospective case-control study on breast cancer nested in the EPIC Italy cohort and we perform weighted gene-set enrichment analyses to demonstrate the biological meaningfulness of the obtained results. We compared the results of Deep Survival EWAS with those of a traditional EWAS approach, demonstrating that our method performs better than the standard approach in identifying biologically relevant pathways.

While coffee and tea consumption has been associated with risk of diseases, their mechanisms of action remain elusive. Here the authors present a large EWAS on coffee and tea consumption in cohorts of European and African-American ancestries, finding that coffee consumption is associated with differential DNA methylation levels at multiple CpGs.

Background: Although physical activity (PA) has been shown to enhance hypertension control, the impact of exercise on the potential decrease of the use of antihypertensive medications remains inadequately researched. Aim: The aim was to assess the impact of a two-year PA on the medication requirements of individuals with hypertension. Methods: A clinical trial was conducted, involving 130 participants with essential hypertension who took at least one antihypertensive medication. Participants were randomly assigned to either a control group (CG n = 65) or an experimental group (EG n = 65) that underwent a 24-month supervised PA program based on a combination of aerobic and resistance training. The antihypertensive drug load for each participant was determined by adding the ratios of the prescribed daily dose (PDD) to the defined daily dose (DDD) for all antihypertensive medications taken by the participants. The outcome measures were evaluated at 0, 6, 12, 18, and 24 months. Results: A total of 76 participants completed the 24-month assessment, and RM-ANOVA revealed a significantly lower antihypertensive drug load in the EG compared to the CG at 18 (p < 0.017) and 24 months (p < 0.003). Conclusion: A long-term PA program can decrease the antihypertensive drug load in older adults with essential hypertension. The trend of improvement regarding the EG drug load intake and the trend of CG drug load increase, although not significant over time, results in a significant difference between the groups at 18 months and an even greater difference at 24 months. This trend certifies the protective value of PA against the aging process and its related health risk factors.

Recent studies have provided evidence of interactions among the gut microbiota (GM), local host immune cells, and intestinal tissues in colon carcinogenesis. However, little is known regarding the functions exerted by the GM in colon cancer (CC), particularly with respect to tumor clinical classification and lymphocyte infiltration. In addition, stool, usually employed as a proxy of the GM, cannot fully represent the original complexity of CC microenvironment. Here, we present a pilot study aimed at characterizing the metaproteome of CC-associated colonic luminal contents and identifying its possible associations with CC clinicopathological features. Colonic luminal contents were collected from 24 CC tissue specimens immediately after surgery. Samples were analyzed by shotgun metaproteomics. Almost 30,000 microbial peptides were quantified in the samples, enabling the achievement of the taxonomic and functional profile of the tumor-associated colonic luminal metaproteome. Upon sample aggregation based on tumor stage, grade, or tumor-infiltrating lymphocytes (TILs), peptide sets enabling discrimination of sample groups were identified through discriminant analysis (DA). As a result, Bifidobacterium and Bacteroides fragilis were significantly enriched in high-stage and high-grade CC, respectively. Among metabolic functions, formate–tetrahydrofolate ligase was significantly associated with high-stage CC. Finally, based on the results of this pilot study, we assessed the optimal sample size for differential metaproteomic studies analyzing colonic luminal contents. In conclusion, we provide a detailed picture of the microbial and host components of the colonic luminal proteome and propose promising associations between GM taxonomic/functional features and CC clinicopathological features. Future studies will be needed to verify the prognostic value of these data and to fully exploit the potential of metaproteomics in enhancing our knowledge concerning CC progression.

The objective of this systematic review was to examine the effectiveness of flywheel training, which allows for the replication of specific sports movements, overloading both the concentric and eccentric phases. Inclusion criteria were injury prevention outcomes; ability in terms of strength, power, sprinting, jumping and change of direction; competitive athletes; and RCTs. Exclusion criteria were a lack of a control group and lack of baseline and/or follow-up data. The databases used were Web of Science, Scopus, PubMed, Cochrane Library, and Sage. The revised Cochrane risk-of-bias tool was used to assess the quality of the selected RCTs. The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence was used. A PICOS (participants, intervention, comparators, study outcomes, and study design) approach was used to evaluate eligibility. A total of 21 RCTs with 8 to 54 participants in each study analyzed flywheel technology and its application in nine sports. The results showed that flywheel training is a good strategy to improve sports performance, providing variation in training methodologies and athletes’ adherence. Further studies are needed to define guidelines on training modality, weekly frequency, volume, and inertia load. Only a few studies have applied the flywheel device directly to overload specific multidirectional movements at different joint angles. This method is not exempt from criticalities, such as the cost and the ability to carry out only individual training.

The COVID-19 pandemic deeply affected sports and athletes, influencing performance and psychological wellbeing. In order to provide useful guidelines for coaches, a web-based survey was conducted. Three web-based questionnaires were administered during the last phase of the Omicron wave to a total of 204 Italian athletes (age 24.96 ± 9.82): an informative questionnaire to collect sociodemographic data and infection symptoms information, the Fatigue Severity Scale (FSS) and the General Health Questionnaire-12 (GHQ-12). No differences between infection sequels of different variant typologies were found over the long term after the infection. The most frequently declared symptoms included cough (50%), muscular skeletal impairments (48%) fatigue (43%) and fever (43%). Results showed that female athletes have a higher risk of developing post-COVID-19 symptoms, GHQ-12 worse results (p = 0.005) and greater fatigue (p = 0.0002) than males. No significant difference in infection incidence between high- and low-level athletes was found. Endurance athletes showed greater perceived fatigue than anaerobic sports athletes (p = 0.045). Conclusions: These results suggested the need for specific approaches and continuous updating to differentiate training programs for different athletes during the return to play. Medical controls and daily monitoring of athletes of all levels after the infection could be advisable.

Abstract Background We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

The biological mechanisms through which adherence to Mediterranean Diet (MD) protects against colon cancer (CC) are poorly understood. Evidence suggests that chronic inflammation may be implicated in the pathway. Both diet and CC are related to epigenetic regulation. We performed a nested case-control study on 161 pairs from the Italian component of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, in which we looked for the methylation signals in DNA extracted from leucocytes associated with both CC and MD in 995 CpGs located in 48 inflammation genes. The DNA methylation signals detected in this analysis were validated in a subgroup of 47 case-control pairs and further replicated (where validated) in 95 new pairs by means of pyrosequencing. Among the CpG sites selected a-priori in inflammation-related genes, seven CpG sites were found to be associated with CC status and with MD, in line with its protective effect. Only two CpG sites (cg17968347-SERPINE1 and cg20674490-RUNX3) were validated using bisulphite pyrosequencing and, after replication, we found that DNA methylation of cg20674490-RUNX3 may be a potential molecular mediator explaining the protective effect of MD on CC onset. The use of a ‘meet-in-the-middle’ approach to identify the overlap between exposure and predictive markers of disease is innovative in studies on the relationship between diet and cancer, in which exposure assessment is difficult and the mechanisms through which the nutrients exert their protective effect is largely unknown.

Abstract Background Several observational studies have shown that exercise reduces the risk of cognitive decline; however, evidences from long-term, well-conducted, randomized controlled trials are scanty. The principal aim of this study is to verify whether a long-term program of multimodal supervised exercise improves the cognitive function and/or reduces the rate of cognitive decline in older adults at different degrees of risk for dementia. Methods/design EPD is a parallel group, double-blind, randomized controlled trial. Community-dwelling volunteers aged 50 years or more are being recruited from different community centers and screened for eligibility. Enrolled subjects are being divided in 3 groups: a) without subjective or objective cognitive impairment, b) with subjective memory complaints, and c) with mild cognitive impairments. Participants in each group (at least 180) are being randomly assigned (1:1) to an experimental group, performing a supervised training including aerobic and resistance exercises of moderate/high intensity, or to a control group. Primary outcome will be 48-months changes in Mini Mental State Examinations. Secondary outcomes will be changes in several cognitive tests including a composite cognitive score. Time points will be at baseline, and at 6, 12, 24, 36 and 48 months. Statistical analysis will be done as intention to treat, complete case and mixed model analysis. Discussion EPD is the first trial to examine the effects of a long exercise program (48 months) on cognitive performances. If successful, this trial may provide evidence for using long-term and multimodal exercise interventions for dementia prevention programs in the aging population. Trial registration The study is registered at ClinicalTrials.gov with the code NCT02236416.

The specificity of training as well as the specificity of monitoring the training process are believed to be fundamental principles to efficiently plan and carry out the preparation and performance development of athletes. The Anaerobic Intermittent Kick Test (TAIKT) is a sport-specific field test used to specifically evaluate the anaerobic profile of Taekwondo athletes. The aim of this study was to verify whether TAIKT and the ‘gold standard’ Wingate Anaerobic test (WAnT) were both efficient means to optimally determine the anaerobic power and anaerobic capacity of Greek Taekwondo athletes at a middle-high technical level. Fifteen athletes, 10 females and 5 males (mean age 23.4 ± 4.14 years), underwent the two anaerobic tests (TAIKT and WAnT). The peak of power, the anaerobic capacity, and the peak of blood lactate (BL) were recorded. The two tests showed a moderate correlation with the r value ranging between 0.353 and 0.428, if applied to a sample of middle-high technical level athletes. Regarding the peak of BL, data indicated 40% concordance between the two tests with a coefficient of variation of 12%. Consequently, the two tests were correlated even if not interchangeable due to the different type of exercise required in these assessments. In conclusion, to assess the anaerobic performances and physiological characteristics of Taekwondo athletes, independently of their technical level, the WAnT resulted suitable, while to better assess the functional performance and specific demands of Taekwondo, the TAIKT is more indicated.

The outbreak of the 2019 coronavirus disease (COVID-19) created an international public health emergency, challenging the psychological resilience of the general population. Regarding this matter, a web-based survey was performed. Data were collected from the following 1,668 self-selected volunteers: 800 athletes (28.30 ± 10.93 years old); 558 coaches (36.91 ± 11.93 years old); and 310 sports managers (42.07 ± 13.38 years old). To assess the level of psychological stress, an Impact of the Event Scale-Revised (IES-R) questionnaire was used. The results indicated that 34.4% of the participants who were interviewed were affected by subjective distress while 26.4% rated their psychological impact from the sports activity interruption as severe. Separated one-way analysis of variance (ANOVA) tests showed significant differences in the IES-R total score (TS), indicating that the level of stress in terms of gender revealed that women were more stressed than men (p = 0.000), for "sports roles" in which the manager and coaches were more stressed than the athletes (p < 0.05), and "type of sport" in which fitness and individual athletes were more stressed than team athletes (p < 0.01). The middle-level athletes showed significantly more hyperarousal levels than high-level athletes (p = 0.012). The results of this survey may raise awareness of this problem and help athletic associations to have appropriate guidelines in order to better sustain their memberships and organize an optimal resumption of their sports activities. Along these lines, social interactions, which are typical of team sports, are crucial to warrant resilience and psychological health. The athletes by managing independently the new rules and measures, thanks to a clear communication, could improve their adaptive stress reaction.

Abstract Background Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. Results Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This “epigenetic supersimilarity” apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer. Conclusions These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. In addition, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (liver, lung, kidney, small intestine terminal ileum, skin not sun-exposed, and whole blood). Among them, as expected, we confirmed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response-related genes, reinforce the need to overcome the sex bias of clinical trials.

Intergenerational physical activity could be a pleasant method to prevent elderly sedentary behaviors. The aim of this study is to provide a basis to develop an intergenerational physical activity between preschool children and elderly people. An assessing enjoyment three questionnaire survey was administered to 140 participants (aged 67.8 ± 9.1): the global physical activity questionnaire (GPAQ) assessing the sedentariness degree; the physical activity enjoyment scale (PACES-Q) assessing enjoyment for the physical activity usually practiced; the physical activity enjoyment scale (PACES-INT) assessing the enjoyment for a hypothetical intergenerational program. Successively, the sample was divided into subgroups based on age, gender, marital status, education, employment, sports background, sedentariness level and residential location. Four multichoice questions, aiming to have guidelines in organizing an intergenerational program, were used. A total of 44.3% of the sample found the physical activity practiced pleasant, whereas 81.5% enjoyed the intergenerational program (only 7.1% expressed a negative judgment). A separated one-way ANOVA showed significant differences in PACES-INT for gender, (p = 0.009), residential location, (p < 0.001) and employment (p = 0.004). About 80% of the sample would adhere to the intergenerational programs, despite the fatigue fear and logistic or family relationship problems.

Functional inertial training, a popular high-intensity training mode, provides high neuromuscular activation, developing proprioception, postural control, power, and sprint time. Aim of the study was to assess the acute effects of two types of warm-up (WU), inertial warm-up (IWU) vs. traditional warm-up (TWU), on explosive and reactive strength, sprint, and Change of Directions (COD) in young soccer players. In a randomized cross-over design study, twelve soccer players (aged 13.3 ± 0.7) performed 16 min of IWU and 16 min of TWU. IWU and TWU were spaced two weeks apart. Pre and post intervention tests, aimed at assessing explosive and reactive strength, sprint, and COD ability included: Squat Jump test (SJ), Countermovement Jump test (CMJ), Drop Jump test (DJ), Seven Repetition Hopping test (7R-HOP), 40 m-sprint test (40 m), and Illinois Agility Test (IAT). RM-ANOVA, used to compare differences between IWU and TWU effects (the level of significance set at ρ ≤ 0.05), showed enhanced performance after the IWU compared to the TWU. In addition, the effects of the IWU on performance lasted longer after the IWU than after the TWU. For IAT, the enhanced effects of IWU on performance lasted up to ten minutes after the administration of the IWU. Our results suggest that IWU affects functional changes displaying earlier adaptation in explosive and reactive strength with longer lasting effects compared to TWU and it could be recommended in young soccer athletes as a WU procedure.

Elevated levels of C-reactive protein (CRP, determined by a high-sensitivity assay) indicate low-grade inflammation which is implicated in many age-related disorders. Epigenetic studies on CRP might discover molecular mechanisms underlying CRP regulation. We aimed to identify DNA methylation sites related to CRP concentrations in cells and tissues regulating low-grade inflammation.Genome-wide DNA methylation was measured in peripheral blood in 1,741 participants of the KORA F4 study using Illumina HumanMethylation450 BeadChip arrays. Four CpG sites (located at BCL3, AQP3, SOCS3, and cg19821297 intergenic at chromosome 19p13.2, P ≤ 1.01E-07) were significantly hypomethylated at high CRP concentrations independent of various confounders including age, sex, BMI, smoking, and white blood cell composition. Findings were not sex-specific. CRP-related top genes were enriched in JAK/STAT pathways (Benjamini-Hochberg corrected P < 0.05). Results were followed-up in three studies using DNA from peripheral blood (EPICOR, n = 503) and adipose tissue (TwinsUK, n = 368) measured as described above and from liver tissue (LMU liver cohort, n = 286) measured by MALDI-TOF mass spectrometry using EpiTYPER. CpG sites at the AQP3 locus (significant p-values in peripheral blood = 1.72E-03 and liver tissue = 1.51E-03) and the SOCS3 locus (p-values in liver < 2.82E-05) were associated with CRP in the validation panels.Epigenetic modifications seem to engage in low-grade inflammation, possibly via JAK/STAT mediated pathways. Results suggest a shared relevance across different tissues at the AQP3 locus and highlight a role of DNA methylation for CRP regulation at the SOCS3 locus.

In this paper we investigate about the effective distribution of the numbers coprime with the primes up to p_n . More precisely we prove that these numbers form a periodically monotone sequence . Then we examine some properties of this sequence which, in a certain sense, are transferred to the sequence of primes. Moreover we study the distribution of twin and cousin terms within the above sequence . This study also makes furthermore strongly plausible that the set of twin primes as well as the set of cousin primes is infinite.

Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population.

The phenotypic effect of some single nucleotide polymorphisms (SNPs) depends on their parental origin. We present a novel approach to detect parent-of-origin effects (POEs) in genome-wide genotype data of unrelated individuals. The method exploits increased phenotypic variance in the heterozygous genotype group relative to the homozygous groups. We applied the method to >56,000 unrelated individuals to search for POEs influencing body mass index (BMI). Six lead SNPs were carried forward for replication in five family-based studies (of ∼4,000 trios). Two SNPs replicated: the paternal rs2471083-C allele (located near the imprinted KCNK9 gene) and the paternal rs3091869-T allele (located near the SLC2A10 gene) increased BMI equally (beta = 0.11 (SD), P

The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5)) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

Asbestos exposure is the main risk factor for malignant pleural mesothelioma (MPM), a rare aggressive tumor. Nevertheless, only 5-17% of those exposed to asbestos develop MPM, suggesting the involvement of other environmental and genetic risk factors. To identify the genetic risk factors that may contribute to the development of MPM, we conducted a genome-wide association study (GWAS; 370,000 genotyped SNPs, 5 million imputed SNPs) in Italy, among 407 MPM cases and 389 controls with a complete history of asbestos exposure. A replication study was also undertaken and included 428 MPM cases and 1269 controls from Australia. Although no single marker reached the genome-wide significance threshold, several associations were supported by haplotype-, chromosomal region-, gene- and gene-ontology process-based analyses. Most of these SNPs were located in regions reported to harbor aberrant alterations in mesothelioma (SLC7A14, THRB, CEBP350, ADAMTS2, ETV1, PVT1 and MMP14 genes), causing at most a 2-3-fold increase in MPM risk. The Australian replication study showed significant associations in five of these chromosomal regions (3q26.2, 4q32.1, 7p22.2, 14q11.2, 15q14). Multivariate analysis suggested an independent contribution of 10 genetic variants, with an Area Under the ROC Curve (AUC) of 0.76 when only exposure and covariates were included in the model, and of 0.86 when the genetic component was also included, with a substantial increase of asbestos exposure risk estimation (odds ratio, OR: 45.28, 95% confidence interval, CI: 21.52-95.28). These results showed that genetic risk factors may play an additional role in the development of MPM, and that these should be taken into account to better estimate individual MPM risk in individuals who have been exposed to asbestos.

In spite of the common belief of Europe as reasonably homogeneous at genetic level, advances in high-throughput genotyping technology have resolved several gradients which define different geographical areas with good precision. When Northern and Southern European groups were considered separately, there were clear genetic distinctions. Intra-country genetic differences were also evident, especially in Finland and, to a lesser extent, within other European populations. Here, we present the first analysis using the 125,799 genome-wide Single Nucleotide Polymorphisms (SNPs) data of 1,014 Italians with wide geographical coverage. We showed by using Principal Component analysis and model-based individual ancestry analysis, that the current population of Sardinia can be clearly differentiated genetically from mainland Italy and Sicily, and that a certain degree of genetic differentiation is detectable within the current Italian peninsula population. Pair-wise F(ST) statistics Northern and Southern Italy amounts approximately to 0.001 between, and around 0.002 between Northern Italy and Utah residents with Northern and Western European ancestry (CEU). The Italian population also revealed a fine genetic substructure underscoring by the genomic inflation (Sardinia vs. Northern Italy = 3.040 and Northern Italy vs. CEU = 1.427), warning against confounding effects of hidden relatedness and population substructure in association studies.

n this paper we give a new proof of a known diophantine approximation result, then we apply this to prove convergence of a class of series in a Banach space, whose terms are defined recursively.

In this paper we investigate the uniform distribution in [0,T] (T ∊ R+- Q) of a suitable sequence. Then we give an interesting application to the study of a class of series whose terms are defined recursively.

In this paper we prove some theorems that emphasize properties of the series whose terms are defined recursively. Suitable examples and counter-examples complete the theory.