Technical challenges of providing record linkage services for research

Background: Record linkage techniques are widely used to enable health researchers to gain event based longitudinal information for entire populations. The task of record linkage is increasingly being undertaken by specialised linkage units (SLUs). In addition to the complexity of undertaking probabilistic record linkage, these units face additional technical challenges in providing record linkage ‘as a service’ for research. The extent of this functionality, and approaches to solving these issues, has had little focus in the record linkage literature. Few, if any, of the record linkage packages or systems currently used by SLUs include the full range of functions required. Methods: This paper identifies and discusses some of the functions that are required or undertaken by SLUs in the provision of record linkage services. These include managing routine, on-going linkage; storing and handling changing data; handling different linkage scenarios; accommodating ever increasing datasets. Automated linkage processes are one way of ensuring consistency of results and scalability of service. Results: Alternative solutions to some of these challenges are presented. By maintaining a full history of links, and storing pairwise information, many of the challenges around handling ‘open’ records, and providing automated managed extractions are solved. A number of these solutions were implemented as part of the development of the National Linkage System (NLS) by the Centre for Data Linkage (part of the Population Health Research Network) in Australia.Conclusions: The demand for, and complexity of, linkage services are growing. This presents as a challenge to SLUs as they seek to service the varying needs of dozens of research projects annually. Linkage units need to be both flexible and scalable to meet this demand. It is hoped the solutions presented here can help mitigate these difficulties

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

Evaluation of High Resolution Melting analysis as an alternate tool to screen for risk alleles associated with small kidneys in Indian newborns

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are the most common forms of sequence variations in the human genome. They contribute to the human phenotypic spectrum and are associated with variations in response to pathogens, drugs and vaccines. Recently, SNPs in three human genes involved in kidney development (<it>RET</it>, <it>PAX2 </it>and <it>ALDH1A2</it>) have been reported to be associated with variation in renal size and function. These known SNPs could potentially be used in the clinic as markers for identifying babies who may have smaller kidneys and permit close follow up for early detection of hypertension and acquired renal dysfunction. The aim of this study was to evaluate the use of High Resolution Melting technique (HRM) as a tool for detecting the known SNPs in these three genes in comparison to sequencing which is the gold standard.</p> <p>Methods</p> <p>High resolution melting analysis was performed on 75 DNA samples that were previously sequenced for the known polymorphisms in <it>RET </it>(rs1800860), <it>PAX2 </it>(rs11190688) and <it>ALDH1A2 </it>(rs7169289) genes. The SNPs were G > A transitions in <it>RET </it>and <it>PAX2 </it>and A > G in <it>ALDH1A2 </it>gene. A blinded assessment was performed on these samples for evaluation of the HRM technique as compared to sequencing.</p> <p>Results</p> <p>Each variant had a unique melt curve profile that was reproducible. The shift in melting temperature (Tm) allowed visual discrimination between the homozygous alleles (major and minor) in all three genes. The shape of the melting curve as compared to the major allele homozygous curve allowed the identification of the heterozygotes in each of the three SNPs. For validation, HRM was performed on 25 samples for each of the three SNPs. The results were compared with the sequencing results and 100% correct identification of the samples was obtained for <it>RET</it>, <it>PAX2</it>, and <it>ALDA1H2 </it>gene.</p> <p>Conclusion</p> <p>High Resolution Melting analysis is a simple, rapid and cost effective technique that could be used in a large population to identify babies with the risk alleles. These high risk children could be followed up for early detection of hypertension and acquired renal dysfunction.</p

17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

The putative oestrogen receptor negative human breast cancer cell line MDA231, when grown as tumours in mice continually receiving 17β-oestradiol, showed substantially increased growth rate when compared to control animals. Further, we observed that 17β-oestradiol treatment could both increase the growth rate of established MDA231 tumours as well as decreasing the time taken for initiating tumour growth. We have also demonstrated that this increase in growth rate is accompanied by a four-fold increase in nitric oxide synthase activity, which was predominantly the inducible form. Inducible-nitric oxide synthase expression in these tumours was confirmed by immunohistochemical analysis and appeared localized primarily in areas between viable and necrotic regions of the tumour (an area that is presumably hypoxic). Prophylactic treatment with the nitric oxide synthase inhibitor nitro-L-arginine methyl ester resulted in significant reduction in this apparent 17β-oestradiol-mediated growth promoting effect. Tumours derived from mice receiving 17β-oestradiol-treatment were characterized by a significantly lower fraction of perfused blood vessels and an indication of an increased hypoxic fraction. Consistent with these observations, 17β-oestradiol-treated tumours were less radio-responsive compared to control tumours when treated with a single radiation dose of 15 Gy. Our data suggests that long-term treatment with oestrogen could significantly alter the tumour oxygenation status during breast tumour progression, thus affecting response to radiotherapy

Scattering Theory and PT\mathcal{P}\mathcal{T}-Symmetry

We outline a global approach to scattering theory in one dimension that allows for the description of a large class of scattering systems and their $\mathcal{P}$-, $\mathcal{T}$-, and $\mathcal{P}\mathcal{T}$-symmetries. In particular, we review various relevant concepts such as Jost solutions, transfer and scattering matrices, reciprocity principle, unidirectional reflection and invisibility, and spectral singularities. We discuss in some detail the mathematical conditions that imply or forbid reciprocal transmission, reciprocal reflection, and the presence of spectral singularities and their time-reversal. We also derive generalized unitarity relations for time-reversal-invariant and $\mathcal{P}\mathcal{T}$-symmetric scattering systems, and explore the consequences of breaking them. The results reported here apply to the scattering systems defined by a real or complex local potential as well as those determined by energy-dependent potentials, nonlocal potentials, and general point interactions.Comment: Slightly expanded revised version, 38 page

Theta-paced flickering between place-cell maps in the hippocampus

The ability to recall discrete memories is thought to depend on the formation of attractor states in recurrent neural networks. In such networks, representations can be reactivated reliably from subsets of the cues that were present when the memory was encoded, at the same time as interference from competing representations is minimized. Theoretical studies have pointed to the recurrent CA3 system of the hippocampus as a possible attractor network. Consistent with predictions from these studies, experiments have shown that place representations in CA3 and downstream CA1 tolerate small changes in the configuration of the environment but switch to uncorrelated representations when dissimilarities become larger. The kinetics supporting such network transitions, at the subsecond time scale, is poorly understood, however. Here we show that instantaneous transformation of the spatial context (\u2018teleportation\u2019) does not change the hippocampal representation all at once but is followed by temporary bistability in the discharge activity of CA3 ensembles. Rather than sliding through a continuum of intermediate activity states, the CA3 network undergoes a short period of competitive flickering between pre-formed representations for past and present environment, before settling on the latter. Network flickers are extremely fast, often with complete replacement of the active ensemble from one theta cycle to the next. Within individual cycles, segregation is stronger towards the end, when firing starts to decline, pointing to the theta cycle as a temporal unit for expression of attractor states in the hippocampus. Repetition of pattern-completion processes across successive theta cycles may facilitate error correction and enhance discriminative power in the presence of weak and ambiguous input cues

High Antipredatory Efficiency of Insular Lizards: A Warning Signal of Excessive Specimen Collection?

We live-captured lizards on islands in the Gulf of California and the Baja California peninsula mainland, and compared their ability to escape predation. Contrary to expectations, endemic lizard species from uninhabited islands fled from humans earlier and more efficiently than those from peninsular mainland areas. In fact, 58.2% (n = 146) of the lizards we tried to capture on the various islands escaped successfully, while this percentage was only 14.4% (n = 160) on the peninsular mainland. Separate evidence (e.g., proportion of regenerated tails, low human population at the collection areas, etc.) challenges several potential explanations for the higher antipredatory efficiency of insular lizards (e.g., more predation pressure on islands, habituation to humans on the peninsula, etc.). Instead, we suggest that the ability of insular lizards to avoid predators may be related to harvesting by humans, perhaps due to the value of endemic species as rare taxonomic entities. If this hypothesis is correct, predation-related behavioral changes in rare species could provide early warning signals of their over-exploitation, thus encouraging the adoption of conservation measures

Natural killer (NK) cells from killers to regulators: Distinct features between peripheral blood and decidual NK cells

Natural killer (NK) cells are a key component of innate immunity, particularly crucial during the early phase of immune responses against certain viruses, parasites, and microbial pathogens. The role of NK cell during pregnancy has been vividly discussed over the past years and it is now becoming increasingly clear that NK cells control pregnancy maintenance at several levels. In normal pregnancy, it appears that they provide benefit by properly secreting cytokines, chemokines and angiogenic factors rather than functioning as cytotoxic effector cells. However, as they are endowed with all the cytolytic weapons, they promptly become capable of attacking fetal and maternal tissues during infection and inflammation. © 2007 The Authors Journal compilation 2007 Blackwell Munksgaard

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature