Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Spectral Line-by-Line Pulse Shaping of an On-Chip Microresonator Frequency Comb

We report, for the first time to the best of our knowledge, spectral phase characterization and line-by-line pulse shaping of an optical frequency comb generated by nonlinear wave mixing in a microring resonator. Through programmable pulse shaping the comb is compressed into a train of near-transform-limited pulses of \approx 300 fs duration (intensity full width half maximum) at 595 GHz repetition rate. An additional, simple example of optical arbitrary waveform generation is presented. The ability to characterize and then stably compress the frequency comb provides new data on the stability of the spectral phase and suggests that random relative frequency shifts due to uncorrelated variations of frequency dependent phase are at or below the 100 microHertz level.Comment: 18 pages, 4 figure

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

INTRODUCTION: c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. METHODS: In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. RESULTS: Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. CONCLUSION: The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

Childhood abdominal pain in primary care: design and patient selection of the HONEUR abdominal pain cohort

Background: Abdominal pain in children is a common complaint presented to the GP. However, the prognosis and prognostic factors of childhood abdominal pain are almost exclusively studied in referred children. This cohort study aims at describing prognosis and prognostic factors of childhood abdominal pain in primary care. In this paper we describe methods used for data-collection and determine possible selective recruitment. Methods/Design: We conducted an observational, prospective cohort study with a 1-year follow-up. From May 2004 to March 2006, 53 Dutch GPs recruited consecutive children aged 4-17 years with a new episode of abdominal pain not preceded by a consultation for this complaint in the previous 3 months. Participants filled in standardized questionnaires, and faeces and urine were sampled. To evaluate selective recruitment, the electronic medical records of participating GPs were retrospectively searched for eligible non-included children. Discussion: This study allows us to describe prognosis and prognostic factors of childhood abdominal pain in primary care. A total of 305 children were included of whom 142 (46.6%) met predefined criteria for chronic/recurrent abdominal pain at presentation; from the total group of eligible children identified from the electronic medical record, 27% were included. The included children were significantly younger than non-included children (mean age 8.49 and 9.20 years). In proportion to identified eligible children, significantly less children diagnosed with "gastroenteritis" (6.8%) and significantly more children with "generalized abdominal pain" (39%) were included compared to the 27% that was expected. This cohort represents young school-aged children consulting GPs for a new episode of abdominal pain, not diagnosed as gastroenteritis. Almost half of them fulfil the criteria for chronic abdominal pain at presentation

Precision measurement of the η→π+π−π0\eta\to\pi^+\pi^-\pi^0 Dalitz plot distribution with the KLOE detector

Using $1.6$ fb$^{-1}$ of $e^+ e^-\to\phi\to\eta\gamma$ data collected with the KLOE detector at DA$\Phi$NE, the Dalitz plot distribution for the $\eta \to \pi^+ \pi^- \pi^0$ decay is studied with the world's largest sample of $\sim 4.7 \cdot 10^6$ events. The Dalitz plot density is parametrized as a polynomial expansion up to cubic terms in the normalized dimensionless variables $X$ and $Y$. The experiment is sensitive to all charge conjugation conserving terms of the expansion, including a $gX^2Y$ term. The statistical uncertainty of all parameters is improved by a factor two with respect to earlier measurements.Comment: 11 pages, 9 figures, supplement: an ascii tabl

Long-term prognostic significance of HER-2/neu in untreated node-negative breast cancer depends on the method of testing

INTRODUCTION: The prognostic significance of HER-2/neu in breast cancer is a matter of controversy. We have performed a study in 101 node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting, and analysed the prognostic significance of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), both separately and in combination, in comparison with traditional prognostic factors. METHODS: Overexpression was classified semiquantitatively according to a score (0 to 3+) (HER-2_SCO). FISH was used to analyse HER2/neu amplification (HER-2_AMP). Patients classified 2+ by IHC were examined with FISH for amplification (HER-2_ALG). Patients with 3+ overexpression as well as amplification of HER-2/neu were positive for the combined variable HER2_COM. These variables were compared with tumour size, histological grade and hormone receptor status. RESULTS: HER-2_SCO was 3+ in 20% of all tumours. HER-2_ALG was positive in 22% and amplification (HER-2_AMP) was found in 17% of all tumours. Eleven percent of the tumours showed simultaneous 3+ overexpression and amplification. Only histological grade (relative risk [RR] 3.22, 95% confidence interval [CI] 1.73–5.99, P = 0.0002) and HER-2_AMP (RR 2.47, 95% CI 1.12–5.48, P = 0.026) were significant for disease-free survival in multivariate analysis. For overall survival, both histological grade (RR 3.89, 95% CI 1.77–8.55, P = 0.0007) and HER-2_AMP (RR 3.08, 95% CI 1.24–7.66, P = 0.016) retained their independent significance. CONCLUSION: The prognostic significance of HER-2/neu in node-negative breast cancer depends on the method of testing: only the amplification of HER-2/neu is an independent prognostic factor for the long-term prognosis of untreated node-negative breast cancer

Extraordinarily high biomass benthic community on Southern Ocean seamounts

We describe a previously unknown assemblage of seamount-associated megabenthos that has by far the highest peak biomass reported in the deep-sea outside of vent communities. The assemblage was found at depths of 2–2.5 km on rocky geomorphic features off the southeast coast of Australia, in an area near the Sub-Antarctic Zone characterised by high rates of surface productivity and carbon export to the deep-ocean. These conditions, and the taxa in the assemblage, are widely distributed around the Southern mid-latitudes, suggesting the high-biomass assemblage is also likely to be widespread. The role of this assemblage in regional ecosystem and carbon dynamics and its sensitivities to anthropogenic impacts are unknown. The discovery highlights the lack of information on deep-sea biota worldwide and the potential for unanticipated impacts of deep-sea exploitation

Revisiting the Glick-Rogoff Current Account Model: An Application to the Current Accounts of BRICS Countries

Understanding what drives the changes in current accounts is one of the most important macroeconomic issues for developing countries. Excessive surpluses in current accounts can trigger trade wars, and excessive deficits in current accounts can, on the other hand, induce currency crises. The Glick-Rogoff (1995, Journal of Monetary Economics) model, which emphasizes productivity shocks at home and in the world, fit well with developed economies in the 1970s and 1980s. However, the Glick-Rogoff model fits poorly when it is applied to fast-growing BRICS countries for the period including the global financial crisis. We conclude that different mechanisms of current accounts work for developed and developing countries

Ghostwriting at Elite Academic Medical Centers in the United States

Jeffrey Lacasse and Jonathan Leo assess ghostwriting policies at 50 academic medical centers in the United States and find that only 10 explicitly prohibit ghostwriting