Persistently raised C-reactive protein levels are associated with advanced periodontal disease

Objective: The aim was to investigate whether there was an association between periodontitis or tooth loss in a homogeneous group of 60-70-year-old Western European men and either a sustained high or low level of C-reactive protein (CRP).
Material and Methods: Men enrolled in a cohort study of cardiovascular disease in Northern Ireland were screened in 1990-1994 and rescreened in 2001-2004, when a periodontal examination was completed. High-sensitivity CRP was measured from fasting blood samples. There were 806 men with six or more teeth who had either a high level (>3 mg/l) or a lower level of CRP at both time points. Multivariate analysis was carried out using logistic regression with adjustment for possible confounders. Models were constructed with the CRP level as the outcome variable and various measures of periodontal status (low and high threshold periodontitis) or tooth loss as predictor variables. Confounders included in the analysis were known cardiovascular risk factors of age, smoking, diabetes, BMI and socioeconomic status.
Results: There were 67 men who had a high value of CRP (>3 mg/l) and 739 men who had a CRP value =3 mg/l at both time points. The unadjusted odds ratio (OR) for advanced periodontitis to be associated with high CRP was 3.62, p=0.0003. The association was somewhat attenuated but remained significant (OR=2.49, p=0.02) after adjustment for confounders. A high level of tooth loss was also associated with high CRP with an adjusted OR of 2.17, p=0.008. Low threshold periodontitis was not associated with the level of CRP.
Conclusion: There was an association between advanced periodontitis and elevated CRP levels as measured at two time points at a 10-year interval in the 60-70-year-old European males investigated. This association was adjusted for various cardiovascular risk factors. There was also an association between high levels of tooth loss and high CRP in the men studied.

Using CORBA's advanced services to enhance the integrity of QoS management programmable networks

The development of wideband network services and the new network infrastructures to support them have placed much more requirements on current network management systems. Issues such as scalability, integrity and interoperability have become more important. Existing management systems are not flexible enough to support the provision of Quality of Service (QoS) in these dynamic environments. The concept of Programmable Networks has been proposed to address these requirements. Within this framework, CORBA is regarded as a middleware technology that can enable interoperation among the distributed entities founds in Programmable Networks. By using the basic CORBA environment in a heterogeneous network environment, a network manager is able to control remote Network Elements (NEs) in the same way it controls its local resources. Using this approach both the flexibility and intelligence of the overall network management can be improved. This paper proposes the use of two advanced features of CORBA to enhance the QoS management in a Programmable Network environment. The Transaction Service can be used to manage a set of tasks, whenever the management of elements in a network is correlated; and the Concurrency Service can be used to coordinate multiple accesses on the same network resources. It is also shown in this paper that proper use of CORBA can largely reduce the development and administration of network management applications.

Differences in mouse models of diabetes mellitus in studies of male reproduction

Diabetes Mellitus (DM) has been found to have subtle yet profound effects on the metabolic status of the testis, the expression of numerous spermatogenic genes and is associated with increased numbers of sperm with nuclear DNA damage. The precise mechanism causing these detrimental effects remains unknown. The presence of increased levels of the most prominent member (carboxymethyllysine - CML) of the advanced glycation end product adducts and their receptor (RAGE) in the reproductive tract of DM men has provided a new avenue for research. As there are suspicions that the antibiotic (streptozotocin - STZ) employed to induce DM is also capable of causing oxidative stress and DNA damage, we compared CML and RAGE levels in the reproductive tract and sperm nDNA status of STZ mice with the levels in the Ins(2Akita) mouse to determine which more closely mimics the situation described in the human diabetic. CML was observed in the testes, epididymes and sperm of all animals. Sperm from DM mice showed particularly strong CML immunolocalization in the acrosomal cap, the equatorial region and whenever present, cytoplasmic droplets. Although increased, the level of CML on the sperm of the STZ and Ins(2Akita) DM mice did not reach statistical significance. RAGE was present on the developing acrosome and epididymal sperm of all animals and in discrete regions of the epididymes of the DM models. Only the epididymal sperm of the Ins(2Akita) mice were found to have significantly increased (p < 0.0001) nDNA damage. The Ins(2Akita) mouse therefore appears to more accurately reflect the conditions found in the human and, as such, is a more representative model for the study of diabetes and glycation's influence on male fertility.

Customs-Related Transaction Costs, Firm Size and International Trade Intensity

Customs are generally perceived as a time-consuming impediment to international trade. However, few studies have empirically examined the determinants and the impact of this type of government-imposed transaction costs. This paper analyses the role of firm size as a determinant of customs-related transaction costs, as well as the effect of firm size on the relationship between these costs and the international trade intensity of firms. The results of this study indicate that customs-related transaction costs repress international trade activities of firms, even at low levels of these costs. The paper identifies transaction-related economies of scale, simplified customs procedures and advanced information and communication technology as main determinants of customs-related transaction costs. It is shown that when these factors are taken into account, firm size has no effect on customs-related transaction costs. Policy implications are considered for firm strategy and public policy.

A review of radio channel models for body centric communications

The human body is an extremely challenging environment for the operation of wireless communications systems, not least because of the complex antenna-body electromagnetic interaction effects which can occur. This is further compounded by the impact of movement and the propagation characteristics of the local environment which all have an effect upon body centric communications channels. As the successful design of body area networks (BANs) and other types of body centric system is inextricably linked to a thorough understanding of these factors, the aim of this paper is to conduct a survey of the current state of the art in relation to propagation and channel models primarily for BANs but also considering other types of body centric communications. We initially discuss some of the standardization efforts performed by the Institute of Electrical and Electronics Engineers 802.15.6 task group before focusing on the two most popular types of technologies currently being considered for BANs, namely narrowband and Ultrawideband (UWB) communications. For narrowband communications the applicability of a generic path loss model is contended, before presenting some of the scenario specific models which have proven successful. The impacts of human body shadowing and small-scale fading are also presented alongside some of the most recent research into the Doppler and time dependencies of BANs. For UWB BAN communications, we again consider the path loss as well as empirical tap delay line models developed from a number of extensive channel measurement campaigns conducted by research institutions around the world. Ongoing efforts within collaborative projects such as Committee on Science and Technology Action IC1004 are also described. Finally, recent years have also seen significant developments in other areas of body centric communications such as off-body and body-to-body communications. We highlight some of the newest relevant research in these areas as well as discussing some of the advanced topics which are currently being addressed in the field of body centric communications. Key Points Channel models for body centric comms ©2014. The Authors.

Natural Killer Cell-like signature observed in locally advanced rectal cancer after neoadjuvant chemoradiotherapy in a tumour regression grade dependent manner

Background: Around 10-15% of patients with locally advanced rectal cancer (LARC) undergo a pathologically complete response (TRG4) to neoadjuvant chemoradiotherapy; the rest of patients exhibit a spectrum of tumour regression (TRG1-3). Understanding therapy-related genomic alterations may help us to identify underlying biology or novel targets associated with response that could increase the efficacy of therapy in patients that do not benefit from the current standard of care.
Methods: 48 FFPE rectal cancer biopsies and matched resections were analysed using the WG-DASL HumanHT-12_v4 Beadchip array on the illumina iScan. Bioinformatic analysis was conducted in Partek genomics suite and R studio. Limma and glmnet packages were used to identify genes differentially expressed between tumour regression grades. Validation of microarray results will be carried out using IHC, RNAscope and RT-PCR.
Results: Immune response genes were observed from supervised analysis of the biopsies which may have predictive value. Differential gene expression from the resections as well as pre and post therapy analysis revealed induction of genes in a tumour regression dependent manner. Pathway mapping and Gene Ontology analysis of these genes suggested antigen processing and natural killer mediated cytotoxicity respectively. The natural killer-like gene signature was switched off in non-responders and on in the responders. IHC has confirmed the presence of Natural killer cells through CD56+ staining.
Conclusion: Identification of NK cell genes and CD56+ cells in patients responding to neoadjuvant chemoradiotherapy warrants further investigation into their association with tumour regression grade in LARC. NK cells are known to lyse malignant cells and determining whether their presence is a cause or consequence of response is crucial. Interrogation of the cytokines upregulated in our NK-like signature will help guide future in vitro models.

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial.

BACKGROUND: EGFR overexpression occurs in 27-55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. METHODS: In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 1-21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 1-21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. FINDINGS: Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade ≥ 3 neutropenia 35 [13%] vs 74 [28%]). INTERPRETATION: Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. FUNDING: Amgen, UK National Institute for Health Research Biomedical Research Centre.

Advanced Business Simulations-Incorporating business and process execution data

Key Performance Indicators (KPIs) and their predictions are widely used by the enterprises for informed decision making. Nevertheless , a very important factor, which is generally overlooked, is that the top level strategic KPIs are actually driven by the operational level business processes. These two domains are, however, mostly segregated and analysed in silos with different Business Intelligence solutions. In this paper, we are proposing an approach for advanced Business Simulations, which converges the two domains by utilising process execution & business data, and concepts from Business Dynamics (BD) and Business Ontologies, to promote better system understanding and detailed KPI predictions. Our approach incorporates the automated creation of Causal Loop Diagrams, thus empowering the analyst to critically examine the complex dependencies hidden in the massive amounts of available enterprise data. We have further evaluated our proposed approach in the context of a retail use-case that involved verification of the automatically generated causal models by a domain expert.