Hubble flow variance and the cosmic rest frame

We characterize the radial and angular variance of the Hubble flow in the COMPOSITE sample of 4534 galaxies, on scales in which much of the flow is in the nonlinear regime. With no cosmological assumptions other than the existence of a suitably averaged linear Hubble law, we find with decisive Bayesian evidence (ln B >> 5) that the Hubble constant averaged in independent spherical radial shells is closer to its asymptotic value when referred to the rest frame of the Local Group, rather than the standard rest frame of the Cosmic Microwave Background. An exception occurs for radial shells in the range 40/h-60/h Mpc. Angular averages reveal a dipole structure in the Hubble flow, whose amplitude changes markedly over the range 32/h-62/h Mpc. Whereas the LG frame dipole is initially constant and then decreases significantly, the CMB frame dipole initially decreases but then increases. The map of angular Hubble flow variation in the LG rest frame is found to coincide with that of the residual CMB temperature dipole, with correlation coefficient -0.92. These results are difficult to reconcile with the standard kinematic interpretation of the motion of the Local Group in response to the clustering dipole, but are consistent with a foreground non-kinematic anisotropy in the distance-redshift relation of 0.5% on scales up to 65/h Mpc. Effectively, the differential expansion of space produced by nearby nonlinear structures of local voids and denser walls and filaments cannot be reduced to a local boost. This hypothesis suggests a reinterpretation of bulk flows, which may potentially impact on calibration of supernovae distances, anomalies associated with large angles in the CMB anisotropy spectrum, and the dark flow inferred from the kinematic Sunyaev-Zel'dovich effect. It is consistent with recent studies that find evidence for a non-kinematic dipole in the distribution of distant radio sources.Comment: 37 pages, 9 tables, 13 figures; v2 adds extensive new analysis (including additional subsections, tables, figures); v3 adds a Monte Carlo analysis (with additional table, figure) which further tightens the statistical robustness of the dipole results; v4 adds further clarifications, small corrections, references and discussion of Planck satellite results; v5 typos fixed, matches published versio

Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?

Low lignan status has been reported to be related to an elevated risk of breast cancer. Since lignan status is reduced by antibacterial medications, it is plausible to hypothesize that repeated use of antibiotics may also be a risk factor for breast cancer. History of treatment for urinary tract infection was studied for its prediction of breast cancer among 9461 Finnish women 19–89 years of age and initially cancer-free. During a follow-up in 1973–1991, a total of 157 breast cancer cases were diagnosed. Women reporting previous or present medication for urinary tract infection at baseline showed an elevated breast cancer risk in comparison with other women. The age-adjusted relative risk was 1.34 (95% confidence interval (CI) = 0.98–1.83). The association was concentrated to women under 50 years of age. The relative risk for these women was 1.74 (95% CI 1.13–2.68), whereas it was 0.97 (95% CI 0.59–1.58) for older women. The relative risk in the younger age-group was 1.47 (95% CI 0.73–2.97) during the first 10 years of follow-up, and 1.93 (95% CI 1.11–3.37) for follow-up times longer than 10 years. These data suggest that premenopausal women using long-term medication for urinary tract infections show a possible elevated risk of future breast cancer. The results are, however, still inconclusive and the hypothesis needs to be tested by other studies. © 2000 Cancer ResearchCampaig

Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes

Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D. Skeletal muscle proteome was analyzed by a sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics technique. Our data indicate a downregulation in several proteins involved inmitochondrial electron transport or respiratory chain complex assembly already in IFG and IGT-muscles, with most profound decreases observed in T2D. Additional phosphoproteomic analysis reveals altered phosphorylation in several signaling pathways in IFG, IGT, and T2D muscles, including those regulating glucose metabolic processes, and the structure of muscle cells. These data reveal several alterations present in skeletalmuscle already in prediabetes and highlight impairedmitochondrial energy metabolism in the trajectory from prediabetes into T2D.Peer reviewe

Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia

Incidence of childhood leukaemia was studied among subjects of a vaccine trial in Finland comparing the polysaccharide–diptheria toxoid conjugate and oligosaccharide–CRM197 conjugate Haemophilus influenzae type b conjugate vaccine formulations. Eighty cases of childhood leukaemia were detected: 35 among children on the polysaccharide–diptheria toxoid conjugate arm, and 45 among children on the oligosaccharide–CRM197 conjugate arm, which was not statistically significant

Azulene-based compounds for targeting orexin receptors

A library of 70 000 synthetically accessible azulene-based compounds was virtually screened at the OX2 receptor. Based on the results, a series of azulene derivatives was synthesized and the binding to and activation of both orexin receptor subtypes were assessed. Two most promising binders were determined to have inhibition constants in the 3-9 mu M range and two other compounds showed weak OX2 receptor agonism. Furthermore, three compounds exhibited a concentration-dependent potentiation of the response to orexin-A at the OX1 but not the OX2 receptors. Altogether this data opens new approaches for further development of antagonists, agonists, and potentiators of orexin response based on the azulene scaffold. (C) 2018 Elsevier Masson SAS. All rights reserved.Peer reviewe

Magnetic Resonance Imaging Findings in Finnish Spitz Dogs with Focal Epilepsy

Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were evaluated. General clinical and neurological examinations, blood examination, urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG examination, focal epileptic activity was found in 7 of 11 dogs (64%), and generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast enhancement after gadolinium injection was identified in this dog's right parietal cortex. However, no such changes were observed in repeated magnetic resonance images. Special emphasis was given to seizure history to determine any correlations between seizure intervals and MRI findings. Our results indicate that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity in detecting epileptogenic areas in our patients with focal seizures. Reversible MRI changes in 1 dog could have been caused by seizures

Serum ceruloplasmin and the risk of cancer in Finland.

The relationship between serum ceruloplasmin level and cancer incidence was investigated in a case-control study nested within a longitudinal study of 39,268 Finns participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey carried out in 1968-1972. During a median follow-up of 8 years, 766 cancer cases were identified. Ceruloplasmin levels were determined from stored serum samples collected at the baseline from these cancer cases and from two matched controls per case. The overall incidence of cancer was positively associated with serum ceruloplasmin level. The association was strongest for lung cancer and other cancers related to smoking and, consequently, in males. The smoking-adjusted relative risk of lung cancer among men was 4.3 (95% confidence interval (CI) = 1.8-10.6) in the highest quintile of serum ceruloplasmin as compared with that in the lowest quintile. The corresponding relative risks for cancers related to smoking combined, and for cancers not related to smoking were 3.9 (CI = 1.9-8.4) and 0.9 (CI = 0.6-1.5), respectively. The elevated risk of lung cancer at high concentrations of serum ceruloplasmin persisted after further adjustment for several potential confounding factors such as serum levels of vitamins A and E and selenium. The risk was stronger during the first 6 years of follow-up than later, and strongest during the first 2 years. The most likely explanation of the present results thus is that high serum ceruloplasmin levels in lung cancer are mainly due to occult cancer

A prospective seroepidemiological study of human herpesvirus-8 infection and the risk of multiple myeloma

Presence of the Human Herpesvirus 8 (HHV8) genome has been reported in the bone marrow of multiple myeloma (MM) patients. So far, serological studies of HHV8 and MM have been inconsistent but have not included prospective epidemiological studies. We evaluated whether HHV8 infection is associated with increased risk for MM in a prospective population-based study of 39 000 Finnish subjects who donated serum samples in the period 1968–72. Serum samples from 47 subjects who developed MM during a 23-year follow-up and 224 age, area of residence and sex-matched subjects who remained healthy over a similar follow-up period were evaluated for HHV8 antibodies at enrolment, as assayed both with an immunofluorescence assay (IFA) for lytic and latent HHV8 antigens and by Western blot (WB) with three recombinant HHV8 proteins (ORFs 65, 73 and K8.1A). HHV8 seropositivity for at least one HHV8 protein on WB was found in 7% of the Finnish population and was not associated with the risk of developing MM (Relative Risk (RR) = 0.89, Confidence Interval (CI): 0.25–3.25). HHV8 seropositivity for lytic and latent antigens in the IFA was found in 16% and 0.4% of the Finnish population and tended to associate with risk of MM (RR = 2.02, CI: 0.94–4.33 and RR = 10.00, CI: 0.91–110.29, respectively). In conclusion, no statistically significant evidence for an association between HHV8 infection and the risk of future MM was found. © 2001 Cancer Research Campaign http://www.bjcancer.co