DNA damage in paediatric obesity: a promoter and predictor of cancer in adulthood

Obesity in children is one of the most serious, global, public health challenges of the 21st century. The accumulation of adipose tissue is associated with a range of metabolic complications including diabetes, cardiovascular disease and dyslipidaemia. Epidemiological evidence links obesity in childhood with developing certain types of cancer later in life. It is postulated that excess adipose tissue and consequent inflammation derived oxidative stress may inflict an accumulation of deleterious DNA mutations and promote genome instability and drive carcinogenesis. Furthermore, a deficiency in micronutrients that are essential for DNA repair may exacerbate this pathological state. This research combined the assessment of anthropometric, inflammatory, micro-nutritional and DNA damage biomarkers via non-invasive techniques. In total, 112 children were recruited from schools and NHS obesity clinics. Anthropometric markers assessed were waist to hip ratio, body fat percentage via bioelectrical impedance, and body mass index standard deviation scores (BMI-SDS). These markers were used to classify participants as obese or nonobese and used for correlational analysis. Inflammation and micronutrient status were determined via C-reactive protein and vitamin D Enzyme Immune Assay (EIA) in saliva. DNA damage assessments include a microscopic assessment of nuclear anomalies via the buccal cytome assay, salivary telomere length via quantitative Polymerase Chain Reaction (qPCR) and urinary 8- hydroxyguanosine (8-OHdG) via EIA. The results from this study indicate obesity to be concurrent with increased inflammation and vitamin D deficiency in this cohort of participants. In addition, obesity was associated with increased oxidative DNA damage (8-OHdG) in urine and DNA damage events in the buccal mucosa. Salivary telomere length was positively correlated with obesity and the total frequency of nuclear anomalies found in buccal epithelial cells. Furthermore, there was a negative correlation between vitamin D and the frequency of nuclear anomalies in the oral cavity. Importantly, odds ratio analysis indicates a high BMI Z-score, waist circumference, body fat percentage, salivary CRP and low salivary vitamin D to be independent risk factors for increased nuclear anomalies in the buccal mucosa. This research is the first to accrue evidence for acquired DNA damage in multiple tissues obtained non-invasively from children with obesity. Our findings instigate that biomonitoring of ‘genome health’ for pre-cancerous molecular and morphological markers in obese patients may inform prioritization and severity of clinical intervention measures to prevent malignancy

Experimental and Atomistic Theoretical Study of Degree of Polarization from Multi-layer InAs/GaAs Quantum Dots

Recent experimental measurements, without any theoretical guidance, showed that isotropic polarization response can be achieved by increasing the number of QD layers in a QD stack. Here we analyse the polarization response of multi-layer quantum dot stacks containing up to nine quantum dot layers by linearly polarized PL measurements and by carrying out a systematic set of multi-million atom simulations. The atomistic modeling and simulations allow us to include correct symmetry properties in the calculations of the optical spectra: a factor critical to explain the experimental evidence. The values of the degree of polarization (DOP) calculated from our model follows the trends of the experimental data. We also present detailed physical insight by examining strain profiles, band edges diagrams and wave function plots. Multi-directional PL measurements and calculations of the DOP reveal a unique property of InAs quantum dot stacks that the TE response is anisotropic in the plane of the stacks. Therefore a single value of the DOP is not sufficient to fully characterize the polarization response. We explain this anisotropy of the TE-modes by orientation of hole wave functions along the [-110] direction. Our results provide a new insight that isotropic polarization response measured in the experimental PL spectra is due to two factors: (i) TM[001]-mode contributions increase due to enhanced intermixing of HH and LH bands, and (ii) TE[110]-mode contributions reduce significantly due to hole wave function alignment along the [-110] direction. We also present optical spectra for various geometry configurations of quantum dot stacks to provide a guide to experimentalists for the design of multi-layer QD stacks for optical devices. Our results predict that the QD stacks with identical layers will exhibit lower values of the DOP than the stacks with non-identical layers.Comment: 10 pages, 7 figures, and 1 tabl

Distributing the Kalman Filter for Large-Scale Systems

This paper derives a \emph{distributed} Kalman filter to estimate a sparsely connected, large-scale, $n-$dimensional, dynamical system monitored by a network of $N$ sensors. Local Kalman filters are implemented on the ($n_l-$dimensional, where $n_l\ll n$) sub-systems that are obtained after spatially decomposing the large-scale system. The resulting sub-systems overlap, which along with an assimilation procedure on the local Kalman filters, preserve an $L$th order Gauss-Markovian structure of the centralized error processes. The information loss due to the $L$th order Gauss-Markovian approximation is controllable as it can be characterized by a divergence that decreases as $L\uparrow$. The order of the approximation, $L$, leads to a lower bound on the dimension of the sub-systems, hence, providing a criterion for sub-system selection. The assimilation procedure is carried out on the local error covariances with a distributed iterate collapse inversion (DICI) algorithm that we introduce. The DICI algorithm computes the (approximated) centralized Riccati and Lyapunov equations iteratively with only local communication and low-order computation. We fuse the observations that are common among the local Kalman filters using bipartite fusion graphs and consensus averaging algorithms. The proposed algorithm achieves full distribution of the Kalman filter that is coherent with the centralized Kalman filter with an $L$th order Gaussian-Markovian structure on the centralized error processes. Nowhere storage, communication, or computation of $n-$dimensional vectors and matrices is needed; only $n_l \ll n$ dimensional vectors and matrices are communicated or used in the computation at the sensors

Sustaining Economic Development by Reforming Basic Institutions through Community Participation

It is universally accepted and advocated that without community involvement and participation, development initiatives either in the economic or social sector, have little chances of success/sustainability, especially at the grassroots level, where the majority of the country’s population lives [AKRSP (1984, 1999); FAO (1989); Khan et al. (1984) and Mustafa (1998)]. In this connection the concept and approaches of community development have been tested in Northern Areas of Pakistan and the principles and experiences have been replicated in some other parts of the country by Non Government Organisations (NGOs), different national and international government projects and programmes [Mustafa and Grunewald (1996); NRMP (1993) and NRSP (1995)]. The need for conceptualising a realistic framework for collaboration between government/other development agencies and community organisations engaged in pursuit of both social and economic goals is imperative for an equitable and sustainable development because when it comes to community involvement, the two sectors cannot be divorced from each other [Khan (1999) and Reid and Khan (1996)]. The objectives of the paper are: to highlight the need and the importance of grassroots non-government institutions based on participatory community development approaches; to analyse the role of community participation models in the country and to recommend strategies for an effective linkage between grassroots non-government organisations and basic-services-driven government institutes for effective and sustainable development; also to review and recommend primitive structural changes in basic institutions as development partners.

Acquired DNA damage in adolescent obesity – a promoter and predictor of cancer?

Introduction Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity coincides with deficiencies in micronutrients such as Vitamin D, a key player in DNA repair processes. As a result, vitamin D deficiency in obesity may have a marked impact on DNA stability and integrity. 8-hydroxyguanosine (8-OHdG) is a well-established marker of oxidative DNA damage that has been identified in higher concentrations in cancer patients. Here we report, preliminary, unpublished findings from our study on acquired DNA damage in childhood obesity. Material and Method Body Mass Index (BMI), Waist to Hip ratio (WHR) and body fat percentage via bioelectrical impedance was assessed in over 70 participants, aged 11-18 and recruited from National Health Service (NHS) obesity clinics and schools in London. A non-invasive, integrated evaluation of urinary 8-OHdG and salivary vitamin D was conducted using ELISA based methods and compared to markers of adiposity. Results and Discussion A BMI percentile >99 was found to be associated with decreased salivary vitamin D and increased urinary 8-OHdG when compared to healthy weight controls (BMI = 5th-85th percentile). Vitamin D levels in saliva were found to be inversely correlated with BMI and body fat percentage. Urinary 8-OHdG positively correlated with body fat percentage and WHR. Most importantly, an inverse correlation between vitamin D in saliva and 8-OHdG in urine was also identified. Recent evidence has suggested vitamin D in obesity to be a consequence of altered behaviour, reduced intestinal absorption, and sequestration of vitamin D into adipose tissue. As a result, DNA repair processes against oxidative DNA damage in obesity may be impaired, resulting in the excess of lesions including 8-OHdG. The effects of excess 8-OHdG lesions have been well researched to include various mutations that can drive carcinogenesis. Conclusion Our results suggest Vitamin D deficiency in obese adolescents may play a significant role in triggering oxidative DNA damage, thus increasing the likelihood of cancer later in life

Genome Instability in Childhood Obesity – a potential role for bariatric surgery in cancer prevention?

Severe paediatric obesity is associated with a range of metabolic complications and is characterised by a chronic meta-inflammatory state. It is postulated that this inflammatory response may result in an excess of systemic reactive oxygen species (ROS) that are well known for inducing DNA damage and reducing the capability of DNA synthesis and repair enzymes. Consequently, chronic inflammation in obesity may promote an accumulation of deleterious DNA mutations, leading to genome instability and driving carcinogenesis. This research aims to accrue evidence to consolidate or refute a causative link between genome instability in childhood obesity and the increased risk of developing cancer at a later stage in life. For the purpose of this study, a novel, non- invasive analytical ‘tool-kit’ for the combined and comprehensive assessment of systemic inflammation and acquired DNA damage has been developed and is being tested on a cohort of severely obese children and healthy weight controls recruited from King’s College Hospital and St George’s NHS trust. Furthermore, this research aims to propose biomonitoring of the genome to inform prioritization and severity of intervention measures based on the suggested reversibility of DNA damage following early surgical weight-loss treatment

DILAND: An Algorithm for Distributed Sensor Localization with Noisy Distance Measurements

In this correspondence, we present an algorithm for distributed sensor localization with noisy distance measurements (DILAND) that extends and makes the DLRE more robust. DLRE is a distributed sensor localization algorithm in $\mathbb{R}^m$ $(m\geq1)$ introduced in \cite{usman_loctsp:08}. DILAND operates when (i) the communication among the sensors is noisy; (ii) the communication links in the network may fail with a non-zero probability; and (iii) the measurements performed to compute distances among the sensors are corrupted with noise. The sensors (which do not know their locations) lie in the convex hull of at least $m+1$ anchors (nodes that know their own locations.) Under minimal assumptions on the connectivity and triangulation of each sensor in the network, this correspondence shows that, under the broad random phenomena described above, DILAND converges almost surely (a.s.) to the exact sensor locations.Comment: Submitted to the IEEE Transactions on Signal Processing. Initial submission on May 2009. 12 page