Study of DX center in Cd0.8Zn0.2Te:CI by positron annihilation

Variable energy positron beam and positron annihilation lifetime experiments have been carried out to study the DX center in Cd0.8Zn0.2Te:Cl at 50 K. A short positron effective diffusion length of 275±25 Å and a large intensity of 79.0%±0.3% for the long lifetime component indicate a strong trapping effect at DX centers. A trapping rate of κ=1.53±0.05×109 s-1 and a positron lifetime of 335±2 ps at the DX center were obtained. The concentration of DX centers is found to be 5.9 ±0.7×1016 cm-3, which is in good agreement with the results obtained using Hall effect and thermo-electric effect measurements. © 1998 American Institute of Physics.published_or_final_versio

Maternal and neonatal risk factors for childhood type 1 diabetes: a matched case-control study

Peer reviewedPublisher PD

Nationwide monitoring of end-of-life care via the Sentinel Network of General Practitioners in Belgium: the research protocol of the SENTI-MELC study

<p>Abstract</p> <p>Background</p> <p>End-of-life care has become an issue of great clinical and public health concern. From analyses of official death certificates, we have societal knowledge on how many people die, at what age, where and from what causes. However, we know little about how people are dying. There is a lack of population-based and nationwide data that evaluate and monitor the circumstances of death and the care received in the final months of life. The present study was designed to describe the places of end-of-life care and care transitions, the caregivers involved in patient care and the actual treatments and care provided to dying patients in Belgium. The patient, residence and healthcare characteristics associated with these aspects of end-of-life care provision will also be studied. In this report, the protocol of the study is outlined.</p> <p>Methods/Design</p> <p>We designed a nationwide mortality follow-back study with data collection in 2005 and 2006, via the nationwide Belgian Sentinel Network of General Practitioners (GPs) i.e. an existing epidemiological surveillance system representative of all GPs in Belgium, covering 1.75% of the total Belgian population. All GPs were asked to report weekly, on a standardized registration form, every patient (>1 year) in their practice who had died, and to identify patients who had died "non-suddenly." The last three months of these patients' lives were surveyed retrospectively. Several quality control measures were used to ensure data of high scientific quality.</p> <p>Discussion</p> <p>In 2005 and 2006, respectively 1385 and 1305 deaths were identified of which 66% and 63% died non-suddenly. The first results are expected in 2007. Via this study, we will build a descriptive epidemiological database on end-of-life care provision in Belgium, which might serve as baseline measurement to monitor end-of-life care over time. The study will inform medical practice as well as healthcare authorities in setting up an end-of-life care policy. We publish the protocol here to inform others, in particular countries with analogue GP surveillance networks, on the possibilities of performing end-of-life care research. A preliminary analysis of the possible strengths, weaknesses and opportunities of our research is outlined.</p

Identification of a human neonatal immune-metabolic network associated with bacterial infection

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis

Fibroblast-derived MT1-MMP promotes tumor progression in vitro and in vivo

BACKGROUND: Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. METHODS: The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. RESULTS: Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels. WT fibroblasts stimulated FaDu tumor cell invasion in coculture. This invasive phenotype was unaffected by combination with MMP-9 null fibroblasts, reduced with MMP-2 null fibroblasts (50%) and abrogated in MT1-MMP null fibroblasts. Co-injection of FaDu tumor cells with fibroblasts in an orthotopic oral cavity SCID mouse model demonstrated a reduction of tumor volume using MMP-9 and MMP-2 null fibroblasts (48% and 49%, respectively) compared to WT fibroblasts. Consistent with in vitro studies, MT1-MMP null fibroblasts when co-injected with FaDu cells resulted in a 90% reduction in tumor volume compared to FaDu cells injected with WT fibroblasts. CONCLUSION: These data suggest a role for fibroblast-derived MMP-2 and MT1-MMP in HNSCC tumor invasion in vitro and tumor growth in vivo

Genotyping with a 198 Mutation Arrayed Primer Extension Array for Hereditary Hearing Loss: Assessment of Its Diagnostic Value for Medical Practice

Molecular diagnostic testing of individuals with congenital sensorineural hearing loss typically begins with DNA sequencing of the GJB2 gene. If the cause of the hearing loss is not identified in GJB2, additional testing can be ordered. However, the step-wise analysis of several genes often results in a protracted diagnostic process. The more comprehensive Hereditary Hearing Loss Arrayed Primer Extension microarray enables analysis of 198 mutations across eight genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5, MTRNR1 and MTTS1) in a single test. To evaluate the added diagnostic value of this microarray for our ethnically diverse patient population, we tested 144 individuals with congenital sensorineural hearing loss who were negative for biallelic GJB2 or GJB6 mutations. The array successfully detected all GJB2 changes previously identified in the study group, confirming excellent assay performance. Additional mutations were identified in the SLC26A4, SLC26A5 and MTRNR1 genes of 12/144 individuals (8.3%), four of whom (2.8%) had genotypes consistent with pathogenicity. These results suggest that the current format of this microarray falls short of adding diagnostic value beyond the customary testing of GJB2, perhaps reflecting the array's limitations on the number of mutations included for each gene, but more likely resulting from unknown genetic contributors to this phenotype. We conclude that mutations in other hearing loss associated genes should be incorporated in the array as knowledge of the etiology of hearing loss evolves. Such future modification of the flexible configuration of the Hereditary Hearing Loss Arrayed Primer Extension microarray would improve its impact as a diagnostic tool

Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342

INTRODUCTION: The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. METHODS: Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m(2), adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. RESULTS: Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). CONCLUSION: None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival

Methods of identifying and recruiting older people at risk of social isolation and loneliness: A mixed methods review

BackgroundLoneliness and social isolation are major determinants of mental wellbeing, especially among older adults. The effectiveness of interventions to address loneliness and social isolation among older adults has been questioned due to the lack of transparency in identifying and recruiting populations at risk. This paper aims to systematically review methods used to identify and recruit older people at risk of loneliness and social isolation into research studies that seek to address loneliness and social isolation.MethodsIn total, 751 studies were identified from a structured search of eleven electronic databases combined with hand searching of reference bibliography from identified studies for grey literature. Studies conducted between January 1995 and December 2017 were eligible provided they recruited community living individuals aged 50 and above at risk of social isolation or loneliness into an intervention study.ResultA total of 22 studies were deemed eligible for inclusion. Findings from these studies showed that the most common strategy for inviting people to participate in intervention studies were public-facing methods including mass media and local newspaper advertisements. The majority of participants identified this way were self-referred, and in many cases self-identified as lonely. In most cases, there was no standardised tool for defining loneliness or social isolation. However, studies that recruited via referral by recognised agencies reported higher rates of eligibility and enrolment. Referrals from primary care were only used in a few studies. Studies that included agency referral either alone or in combination with multiple forms of recruitment showed more promising recruitment rates than those that relied on only public facing methods. Further research is needed to establish the cost-effectiveness of multiple forms of referral.ConclusionFindings from this study demonstrate the need for transparency in writing up the methods used to approach, assess and enrol older adults at risk of becoming socially isolated. None of the intervention studies included in this review justified their recruitment strategies. The ability of researchers to share best practice relies greatly on the transparency of research

Self-medication with over-the-counter drugs and complementary medications in South Australia's elderly population

A number of surveys have examined use of complementary and alternative medicines (CAM) in Australia. However, there are limited Australian data on use of CAM and over-the-counter (OTC) medicines in the elderly population. The main aims of this study were to examine self-medication practices with CAM and OTC medicines among older Australians and variables associated with their use. Participants seemed to self-medicate in accordance with approved indications, suggesting they were informed consumers, actively looking after their own health. However, use of analgesics and aspirin are associated with an increased risk of adverse drug events in the elderly. Future work should examine how self-medication contributes to polypharmacy and increases the risk of adverse drug reactions