Immunodetectable cyclin D 1 is associated with oestrogen receptor but not Ki67 in normal, cancerous and precancerous breast lesions

Cyclin D1 is associated with cell cycle regulation and has more recently been shown to stimulate the transcriptional functions of the oestrogen receptor (ER). Furthermore, in normal breast there is a negative association between expression of ER and the proliferation marker Ki67 indicating that either ER positive cells are non-dividing or that the receptor is down-regulated as cells enter cycle. This important relationship breaks down in many ER-positive cancers and precancerous breast lesions where the receptor is often detected on proliferating cells. The aims of the present study were to determine the interplay between ER, Ki67 and cyclin D 1 in individual cells within the spectrum of human breast lesions ranging from normal to invasive carcinoma by using dual staining immunofluorescence. We found that in normal breast there was a strong positive association between ER and cyclin D 1 expression. In contrast there was a strong negative association between cyclin D 1 and Ki67 expression. Similar findings were seen for the other precancerous and cancerous breast lesions. Thus immunodetectable cyclin D 1 within individual cells does not appear to be associated with cell cycle progression in the benign or malignant breast but instead may have important interactions with ER. © 2001 Cancer Research Campaign http://www.bjcancer.co

Flip Graphs of Degree-Bounded (Pseudo-)Triangulations

We study flip graphs of triangulations whose maximum vertex degree is bounded by a constant $k$. In particular, we consider triangulations of sets of $n$ points in convex position in the plane and prove that their flip graph is connected if and only if $k > 6$; the diameter of the flip graph is $O(n^2)$. We also show that, for general point sets, flip graphs of pointed pseudo-triangulations can be disconnected for $k \leq 9$, and flip graphs of triangulations can be disconnected for any $k$. Additionally, we consider a relaxed version of the original problem. We allow the violation of the degree bound $k$ by a small constant. Any two triangulations with maximum degree at most $k$ of a convex point set are connected in the flip graph by a path of length $O(n \log n)$, where every intermediate triangulation has maximum degree at most $k+4$.Comment: 13 pages, 12 figures, acknowledgments update

A Sparse Stress Model

Force-directed layout methods constitute the most common approach to draw general graphs. Among them, stress minimization produces layouts of comparatively high quality but also imposes comparatively high computational demands. We propose a speed-up method based on the aggregation of terms in the objective function. It is akin to aggregate repulsion from far-away nodes during spring embedding but transfers the idea from the layout space into a preprocessing phase. An initial experimental study informs a method to select representatives, and subsequent more extensive experiments indicate that our method yields better approximations of minimum-stress layouts in less time than related methods.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Research priorities for improving infant and young child feeding in humanitarian emergencies

Background There are many challenges during emergencies to ensure that optimal infant and young child feeding is protected, promoted and supported, but there is a dearth of evidence on strategies and programmes to improve Infant and Young Child Feeding in Emergencies (IYCF-E) and a need to determine research priorities. Methods Based on interviews with key informants who are experts in the subject, we developed a list of 48 research questions on IYCF-E. A framework, following the Child Health and Nutrition Research Initiative method to set priorities in child health research, was developed to rank the research questions. Four criteria were applied to create a ranking based on answerability, operational relevance, disease burden reduction and prevention, and originality. Using an on-line survey, prioritisation of research questions was done by 27 people from 14 NGOs, universities and research institutions, and UN organisations. Results The top-ten research questions identified focused on the following: • Use of cash-transfer to buy breast-milk substitutes; • Effectiveness of complementary feeding strategies; • Long-term effect of IYCF-E interventions; • Design of IYCF-E programmes in a context where breastfeeding rates are low and breast milk substitutes use is high; • Design of effective re-lactation interventions; • Provision of psychological support to young children’s care-takers; • Determination of number of beneficiaries and coverage of IYCF-E programmes; • Pros and cons of distributing ready-to-use infant formula compared with distributing powdered infant formula plus kit for safer use of BMS, when use of infant formula is necessary; • Assessment of the impact of specific IYCF-E programmes on nutritional status, morbidity and mortality; • Linking and mainstreaming IYCF-E interventions with other sectors such as health, WASH, food security and child protection. Conclusion The questions found by this study could form the basis of future research on IYCF-E and could be integrated into the agenda of relevant stakeholders. Results of studies based on these questions will be fundamental to fill the evidence gap in IYCF-E, improve IYCF-E programming and ultimately contribute to the reduction in morbidity and mortality among infants and young children in humanitarian emergencies

Rituximab Unveils Hypogammaglobulinemia and Immunodeficiency in Children with Autoimmune Cytopenia

BACKGROUND: Rituximab (RTX; anti-CD20 mAb) is a treatment option in children with refractory immune thrombocytopenia, autoimmune hemolytic anemia (AHA), and Evans syndrome (ES). Prevalence and clinical course of RTX-induced hypogammaglobulinemia in these patients are poorly known. OBJECTIVE: To evaluate the prevalence and risk factors for persistent hypogammaglobulinemia (PH) after RTX use. METHODS: Clinical and immunologic data from children treated with RTX for immune thrombocytopenia, AHA, and ES were collected from 16 Italian centers and 1 UK center at pre-RTX time point (0), +6 months, and yearly, up to 4 years post-RTX. Patients with previously diagnosed malignancy or primary immune deficiency (PID) were excluded. RESULTS: We analyzed 53 children treated with RTX for immune thrombocytopenia (n = 36), AHA (n = 13), and ES (n = 4). Median follow-up was 30 months (range, 12-48). Thirty-two percent of patients (17 of 53) experienced PH, defined as IgG levels less than 2 SD for age at last follow-up (>12 months after RTX). Significantly delayed B-cell recovery was observed in children experiencing PH (hazard ratio, 0.55; P < .05), and 6 of 17 (35%) patients had unresolved B-cell lymphopenia at last follow-up. PH was associated with IgA and IgM deficiency, younger age at RTX use (51 vs 116 months; P < .01), a diagnosis of AHA/ES, and better response to RTX. Nine patients with PH (9 of 17 [53%]) were eventually diagnosed with a PID. CONCLUSIONS: Post-RTX PH is a frequent condition in children with autoimmune cytopenia; a sizable proportion of patients with post-RTX PH were eventually diagnosed with a PID. In-depth investigation for PID is therefore recommended in these patients

Grid refinement in the construction of Lyapunov functions using radial basis functions

Lyapunov functions are a main tool to determine the domain of attraction of equilibria in dynamical systems. Recently, several methods have been presented to construct a Lyapunov function for a given system. In this paper, we improve the construction method for Lyapunov functions using Radial Basis Functions. We combine this method with a new grid refinement algorithm based on Voronoi diagrams. Starting with a coarse grid and applying the refinement algorithm, we thus manage to reduce the number of data points needed to construct Lyapunov functions. Finally, we give numerical examples to illustrate our algorithms

White matter structure and myelin-related gene expression alterations with experience in adult rats

White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity measured by DTI. We combined DTI, immunohistochemistry and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. First, we observed experience-induced DTI differences in WM and in grey matter structure. C-Fos mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the MRI WM metrics, indicating that molecular correlates of cortical activity relate to macroscale measures of WM structure. Analysis of myelin-related genes revealed higher myelin basic protein (MBP) mRNA expression. Higher MBP protein expression was also found via immunohistochemistry in WM. Finally, unbiased RNA sequencing analysis identified 134 differentially expressed genes encoding proteins in- volved in functions related to cell proliferation and differentiation, regulation of myelination and neuronal activity modulation. In conclusion, macroscale measures of WM plasticity are supported by both molecular and cellular evidence and confirm that myelination is one of the underlying mechanisms

A variational method based on weighted graph states

In a recent article [Phys. Rev. Lett. 97 (2006), 107206], we have presented a class of states which is suitable as a variational set to find ground states in spin systems of arbitrary spatial dimension and with long-range entanglement. Here, we continue the exposition of our technique, extend from spin 1/2 to higher spins and use the boson Hubbard model as a non-trivial example to demonstrate our scheme.Comment: 36 pages, 13 figure