Generalized Arcsine Law and Stable Law in an Infinite Measure Dynamical System

Limit theorems for the time average of some observation functions in an infinite measure dynamical system are studied. It is known that intermittent phenomena, such as the Rayleigh-Benard convection and Belousov-Zhabotinsky reaction, are described by infinite measure dynamical systems.We show that the time average of the observation function which is not the $L^1(m)$ function, whose average with respect to the invariant measure $m$ is finite, converges to the generalized arcsine distribution. This result leads to the novel view that the correlation function is intrinsically random and does not decay. Moreover, it is also numerically shown that the time average of the observation function converges to the stable distribution when the observation function has the infinite mean.Comment: 8 pages, 8 figure

Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation

Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24–87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 ± 0.55 vs 1.85 ± 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure

S-adenosylmethionine and S-adenosylhomocysteine levels in the aging brain of APP/PS1 Alzheimer mice

Hyperhomocysteinemia and factors of homocysteine metabolism, S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), may play a role in Alzheimer’s disease (AD). With liquid-chromatography-tandem-mass-spectrometry AdoMet and AdoHcy were determined in brains of 8- and 15-month-old APP/PS1 Alzheimer mice, and their possible roles in AD brains investigated. The finding that AdoMet levels do not differ between the genotypes in (young) 8-month-old mice, but are different in (older) 15-month-old APP/PS1 mice compared to their wild-type littermates, suggests that alterations in AdoMet are a consequence of AD pathology rather than a cause. During aging, AdoMet levels decreased in the brains of wild-type mice, whereas AdoHcy levels diminished in both wild type and APP/PS1 mice. The finding that AdoMet levels in APP/PS1 mice are not decreased during aging (in contrast to wild-type mice), is probably related to less demand due to neurodegeneration. No effect of the omega-3 fatty acid docosahexaenoic acid (DHA) or cholesterol-enriched diets on AdoMet or AdoHcy levels were found

Emerging therapies in pheochromocytoma and paraganglioma: Immune checkpoint inhibitors in the starting blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respec-tively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progres-sive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology

Mental Health and Wellbeing of Retired Elite and Amateur Rugby Players and Non-contact Athletes and Associations with Sports-Related Concussion: The UK Rugby Health Project

Background Concerns have intensified over the health and wellbeing of rugby union and league players, and, in particular, about the longer-term effects of concussion. The purpose of this study was to investigate whether there were differences in mental health, sleep and alcohol use between retired elite and amateur rugby code players and non-contact athletes, and to explore associations with sports-related concussion. Methods 189 retired elite (ER, n = 83) and amateur (AR, n = 106) rugby code players (rugby union n = 145; rugby league n = 44) and 65 former non-contact athletes (NC) were recruited to the UK Rugby Health Project between 2016 and 2018. Details on sports participation and concussion history were obtained by questionnaire, which also included questions on mental health, anger, sleep, mood, alcohol use, social connections and retirement from injury. Data were compared between sports groups (ER, AR and NC), between exposure of three or more or five or more concussions and for years in sport. Results ER reported more concussions than AR (5.9 ± 6.3 vs. 3.7 ± 6.3, p = 0.022) and NC (0.4 ± 1.0, p < 0.001). ER had a higher overall negative mental health score (indicating poor mental health) than AR (10.4 ± 6.3 vs. 7.4 ± 6.5, d = 0.47, p = 0.003) and NC (7.1 ± 4.8, d = 0.57, p = 0.006) and a lower overall positive score (indicating good mental health) than NC (8.9 ± 4.1 vs. 10.7 ± 3.4, d = 0.46, p = 0.021). Negative scores were highest and positive scores lowest in those reporting three or more concussions (d = 0.36, p = 0.008; d = 0.28, p = 0.040, respectively) or five or more concussions (d = 0.56, p < 0.001; d = 0.325, p = 0.035, respectively). Reported symptoms for sleep disruption were more prevalent in ER than NC, and in former athletes with three or more concussions (d = 0.41–0.605, p < 0.05). There were no significant differences in alcohol score (p = 0.733). Global anger score and covert anger expression was higher in former athletes with five or more concussions (d = 0.32, p = 0.035; d = 0.37, p = 0.016). AR reported greater attachment to friends than NC (d = 0.46, p = 0.033) and 20% of ER reported that they would not turn to anyone if they had a problem or felt upset about anything. Conclusion There was a significantly higher prevalence of adverse mental health and sleep disruption in ER and in former athletes who reported a higher number of concussions. Anger and irritability were more prevalent in former athletes with a history of five or more concussions. Strategies are needed to address mental health and sleep disturbance in elite rugby code athletes, who are also less likely to seek help should they need it. Further research is needed to elucidate causation, and the neurobiological connection between concussion, sub-concussions and longer-term psychological health and wellbeing

Breast phyllodes tumor : A review of literature and a single center retrospective series analysis

PURPOSE: Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well. METHODS: We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010. RESULTS: Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis. DISCUSSION: Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases

S-adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS

BACKGROUND: This study reports on clinical data from an 8-week open-label study of 20 HIV-seropositive individuals, diagnosed with Major Depressive Disorder (DSM-IV), who were treated with SAM-e (S-Adenosylmethionine). SAM-e may be a treatment alternative for the management of depression in a population reluctant to add another "pill" or another set of related side effects to an already complex highly active antiretroviral therapy (HAART) regimen. METHODS: The Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory (BDI) were used to assess depressive symptomatology from 1,2,4,6 and 8 weeks after initiation of treatment with SAM-e. RESULTS: Data show a significant acute reduction in depressive symptomatology, as measured by both the HAM-D and the BDI instruments. CONCLUSIONS: SAM-e has a rapid effect evident as soon as week 1 (p < .001), with progressive decreases in depression symptom rating scores throughout the 8 week study