Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents

Background/objectives Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status. Subjects/methods We carried out a cross-sectional study with 132 participants, aged 10–18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2′-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay. Results As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability. Conclusions Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures

Biomonitoring and predictive modelling of genomic instability in childhood obesity

Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity in childhood and adolescence is concurrent with a state of chronic, low-grade inflammation, a well-known aetiological factor for DNA damage. In addition, obesity in childhood and adolescence has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. We have conducted research aimed at devising a novel approach for predicting genomic instability in childhood obesity via the combined, non-invasive assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status. We carried out a cross-sectional study with participants, aged 10–18, recruited from schools and paediatric obesity clinics in London. Our results support the hypothesis that childhood obesity is associated with increased genomic instability. Importantly, we have found that obesity, vitamin D and oxidative DNA damage can together predict genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures

An examination of business occupier relocation decision making : distinguishing small and large firm behaviour

This paper explores how business occupiers decide whether and where to relocate. It captures the experience and behaviour of a range of sizes and types of business occupier and subjects their decision-making processes to detailed scrutiny. A linear three-stage decision model is used to sequence and structure interviews with individuals who have intimate involvement with the relocation of 28 firms and organizations in Tyne and Wear, in the north-east of England. The 'constant comparative' method is used to analyse the interview data, from which emerges 18 key concepts, comprising 51 characteristic components. Using an axial approach, these are organized into 10 cross-cutting themes that represent the main areas of consideration or influence on the thinking of the people involved in determining whether a firm or organization should relocate and, if so, where to. The resulting analysis finds that organizations adopt varying degrees of sophistication when making relocation decisions; small firms are more inclined to make decisions based on constrained information; larger organizations adopt a more complex approach. Regardless of firm size, key individuals exert considerable influence over the decision-making process and its outcome

The Relationship between Asthma and Depression in Primary Care Patients: A Historical Cohort and Nested Case Control Study

Asthma and depression are common health problems in primary care. Evidence of a relationship between asthma and depression is conflicting. Objectives: to determine 1. The incidence rate and incidence rate ratio of depression in primary care patients with asthma compared to those without asthma, and 2. The standardized mortality ratio of depressed compared to non-depressed patients with asthma.A historical cohort and nested case control study using data derived from the United Kingdom General Practice Research Database. Participants: 11,275 incident cases of asthma recorded between 1/1/95 and 31/12/96 age, sex and practice matched with non-cases from the database (ratio 1∶1) and followed up through the database for 10 years. 1,660 cases were matched by date of asthma diagnosis with 1,660 controls. Main outcome measures: number of cases diagnosed with depression, the number of deaths over the study period.The rate of depression in patients with asthma was 22.4/1,000 person years and without asthma 13.8 /1,000 person years. The incident rate ratio (adjusted for age, sex, practice, diabetes, cardiovascular disease, cerebrovascular disease, smoking) was 1.59 (95% CI 1.48–1.71). The increased rate of depression was not associated with asthma severity or oral corticosteroid use. It was associated with the number of consultations (odds ratio per visit 1.09; 95% CI 1.07–1.11). The age and sex adjusted standardized mortality ratio for depressed patients with asthma was 1.87 (95% CI: 1.54–2.27).Asthma is associated with depression. This was not related to asthma severity or oral corticosteroid use but was related to service use. This suggests that a diagnosis of depression is related to health seeking behavior in patients with asthma. There is an increased mortality rate in depressed patients with asthma. The cause of this needs further exploration. Consideration should be given to case-finding for depression in this population

Review of HBT or Bose-Einstein correlations in high energy heavy ion collisions

A brief review is given on the discovery and the first five decades of the Hanbury Brown - Twiss effect and its generalized applications in high energy nuclear and particle physics, that includes a meta-review. Interesting and inspiring new directions are also highlighted, including for example source imaging, lepton and photon interferometry, non-Gaussian shape analysis as well as many other new directions. Existing models are compared to two-particle correlation measurements and the so-called RHIC HBT puzzle is resolved. Evidence for a (directional) Hubble flow is presented and the conclusion is confirmed by a successful description of the pseudorapidity dependence of the elliptic flow as measured in Au+Au collisions by the PHOBOS Collaboration.Comment: 14 pages, 1 figure, 8 sub-figures, invited plenary talk at the ICPA-QGP 2005 conference in Kolkata, Indi

The Growth of Black Holes and Their Host Spheroids in (Sub)mm-loud QSOs at High Redshift

We study the growth of black holes and stellar population in spheroids at high redshift using several (sub)mm-loud QSO samples. Applying the same criteria established in an earlier work, we find that, similar to IR QSOs at low redshift, the far-infrared emission of these (sub)mm-loud QSOs mainly originates from dust heated by starbursts. By combining low-z IR QSOs and high-z (sub)mm-loud QSOs, we find a trend that the star formation rate (\Mstardot) increases with the accretion rate (\Mdot). We compare the values of \Mstardot/\Mdot for submm emitting galaxies (SMGs), far-infrared ultraluminous/hyperluminous QSOs and typical QSOs, and construct a likely evolution scenario for these objects. The (sub)mm-loud QSO transition phase has both high \Mdot and \Mstardot and hence is important for establishing the correlation between the masses of black holes and spheroids.Comment: 19 pages,3 figures,submitted to Chin. J. Astron. Astrophys. This paper was first prepared for publication on August 10th, 200

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

Opportunities for mesoscopics in thermometry and refrigeration: Physics and applications

This review presents an overview of the thermal properties of mesoscopic structures. The discussion is based on the concept of electron energy distribution, and, in particular, on controlling and probing it. The temperature of an electron gas is determined by this distribution: refrigeration is equivalent to narrowing it, and thermometry is probing its convolution with a function characterizing the measuring device. Temperature exists, strictly speaking, only in quasiequilibrium in which the distribution follows the Fermi-Dirac form. Interesting nonequilibrium deviations can occur due to slow relaxation rates of the electrons, e.g., among themselves or with lattice phonons. Observation and applications of nonequilibrium phenomena are also discussed. The focus in this paper is at low temperatures, primarily below 4 K, where physical phenomena on mesoscopic scales and hybrid combinations of various types of materials, e.g., superconductors, normal metals, insulators, and doped semiconductors, open up a rich variety of device concepts. This review starts with an introduction to theoretical concepts and experimental results on thermal properties of mesoscopic structures. Then thermometry and refrigeration are examined with an emphasis on experiments. An immediate application of solid-state refrigeration and thermometry is in ultrasensitive radiation detection, which is discussed in depth. This review concludes with a summary of pertinent fabrication methods of presented devices.Comment: Close to the version published in RMP; 59 pages, 35 figure

Documenting the NICU design dilemma: comparative patient progress in open-ward and single family room units

Objective:To test the efficacy of single family room (SFR) neonatal intensive care unit (NICU) designs, questions regarding patient medical progress and relative patient safety were explored. Addressing these questions would be of value to hospital staff, administrators and designers alike. Study Design:This prospective study documented, by means of Institution Review Board-approved protocols, the progress of patients in two contrasting NICU designs. Noise levels, illumination and air quality measurements were included to define the two NICU physical environments. Result:Infants in the SFR unit had fewer apneic events, reduced nosocomial sepsis and mortality, as well as earlier transitions to enteral nutrition. More mothers sustained stage III lactation, and more infants were discharged breastfeeding in the SFR. Conclusion:This study showed the SFR to be more conducive to family-centered care, and to enhance infant medical progress and breastfeeding success over that of an open ward

Harmonising data collection from osteoarthritis studies to enable stratification: recommendations on core data collection from an Arthritis Research UK clinical studies group

Objective. Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies.Methods. An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies.Results. Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above.Conclusions. Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment