Stellar Collisions and Ultracompact X-ray Binary Formation

(abridged) We report the results of SPH calculations of parabolic collisions between a subgiant or slightly evolved red-giant star and a neutron star (NS). Such collisions are likely to form ultracompact X-ray binaries (UCXBs) observed today in old globular clusters. In particular, we compute collisions of a 1.4 Msun NS with realistically modelled parent stars of initial masses 0.8 and 0.9 Msun, each at three different evolutionary stages (corresponding to three different radii R). The distance of closest approach for the initial orbit varies from 0.04 R (nearly head-on) to 1.3 R (grazing). These collisions lead to the formation of a tight binary, composed of the NS and the subgiant or red-giant core, embedded in an extremely diffuse common envelope (CE) typically of mass ~0.1 to 0.3 Msun. Our calculations follow the binary for many hundreds of orbits, ensuring that the orbital parameters we determine at the end of the calculations are close to final. Some of the fluid initially in the envelope of the (sub)giant, from 0.003 to 0.023 Msun in the cases we considered, is left bound to the NS. The eccentricities of the resulting binaries range from about 0.2 for our most grazing collision to about 0.9 for the nearly head-on cases. In almost all the cases we consider, gravitational radiation alone will cause sufficiently fast orbital decay to form a UCXB within a Hubble time, and often on a much shorter timescale. Our hydrodynamics code implements the recent SPH equations of motion derived with a variational approach by Springel & Hernquist and by Monaghan. Numerical noise is reduced by enforcing an analytic constraint equation that relates the smoothing lengths and densities of SPH particles. We present tests of these new methods to help demonstrate their improved accuracy.Comment: 41 pages, 17 figures, accepted by Ap

The role of bisphosphonates in breast cancer: The present and future role of bisphosphonates in the management of patients with breast cancer

At least 25% of patients with breast cancer develop skeletal metastases, with bone the site of disease producing the greatest morbidity. It is apparent that the bisphosphonates present an important component of the treatment strategy. They are now the treatment of choice in tumour-induced hypercalcaemia, and they can reduce bone pain and skeletal complications such as pathological fractures. In addition, bisphosphonates are being increasingly evaluated in the prevention of bone metastases and to prevent and treat cancer therapy-induced osteoporosis. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate

Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomised, placebo-controlled phase III studies

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Digital Signal Processing

Contains reports on twelve research projects.U. S. Navy - Office of Naval Research (Contract N00014-75-C-0951)National Science Foundation (Grant ENG76-24117)National Aeronautics and Space Administration (Grant NSG-5157)Joint Services Electronics Program (Contract DAABO7-76-C-1400)U.S. Navy-Office of Naval Research (Contract N00014-77-C-0196)Woods Hole Oceanographic InstitutionU. S. Navy - Office of Naval Research (Contract N00014-75-C-0852)Department of Ocean Engineering, M.I.T.National Science Foundation subcontract to Grant GX 41962 to Woods Hole Oceanographic Institutio

Metastatic breast carcinoma of the coracoid process: two case reports

<p>Abstract</p> <p>Background</p> <p>The coracoid process of the scapula is a rare site of involvement for metastatic disease or for primary tumors. We are unaware of any reports in the literature of pathologic coracoid process fractures and only one report of metastatic disease to the coracoid.</p> <p>Methods and Results</p> <p>In this case report, we present two cases with metastatic breast carcinoma of the coracoid process, one of which presented with a pathologic fracture of the coracoid.</p> <p>Conclusions</p> <p>An orthopaedic surgeon must be aware of the potential for metastatic disease to the coracoid as they may be the first medical provider to encounter evidence of malignant disease.</p

Bone resorption predicts for skeletal complications in metastatic bone disease

Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0–3 months) and 95 patients over the second 3-month period (4–6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r=0.62, P<0.001 for 0–3 months and r=0.46, P<0.001 for 4–6 months, respectively). Patients with baseline Ntx values greater than or equal to100 nmol mmol−1 creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx <100 (P<0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment

Anti-Transforming Growth Factor ß Antibody Treatment Rescues Bone Loss and Prevents Breast Cancer Metastasis to Bone

Breast cancer often metastasizes to bone causing osteolytic bone resorption which releases active TGFβ. Because TGFβ favors progression of breast cancer metastasis to bone, we hypothesized that treatment using anti-TGFβ antibody may reduce tumor burden and rescue tumor-associated bone loss in metastatic breast cancer. In this study we have tested the efficacy of an anti-TGFβ antibody 1D11 preventing breast cancer bone metastasis. We have used two preclinical breast cancer bone metastasis models, in which either human breast cancer cells or murine mammary tumor cells were injected in host mice via left cardiac ventricle. Using several in vivo, in vitro and ex vivo assays, we have demonstrated that anti-TGFβ antibody treatment have significantly reduced tumor burden in the bone along with a statistically significant threefold reduction in osteolytic lesion number and tenfold reduction in osteolytic lesion area. A decrease in osteoclast numbers (p = 0.027) in vivo and osteoclastogenesis ex vivo were also observed. Most importantly, in tumor-bearing mice, anti-TGFβ treatment resulted in a twofold increase in bone volume (p<0.01). In addition, treatment with anti-TGFβ antibody increased the mineral-to-collagen ratio in vivo, a reflection of improved tissue level properties. Moreover, anti-TGFβ antibody directly increased mineralized matrix formation in calverial osteoblast (p = 0.005), suggesting a direct beneficial role of anti-TGFβ antibody treatment on osteoblasts. Data presented here demonstrate that anti-TGFβ treatment may offer a novel therapeutic option for tumor-induced bone disease and has the dual potential for simultaneously decreasing tumor burden and rescue bone loss in breast cancer to bone metastases. This approach of intervention has the potential to reduce skeletal related events (SREs) in breast cancer survivors

Epigenetic Characterization of the FMR1 Gene and Aberrant Neurodevelopment in Human Induced Pluripotent Stem Cell Models of Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. In addition to cognitive deficits, FXS patients exhibit hyperactivity, attention deficits, social difficulties, anxiety, and other autistic-like behaviors. FXS is caused by an expanded CGG trinucleotide repeat in the 5′ untranslated region of the Fragile X Mental Retardation (FMR1) gene leading to epigenetic silencing and loss of expression of the Fragile X Mental Retardation protein (FMRP). Despite the known relationship between FMR1 CGG repeat expansion and FMR1 silencing, the epigenetic modifications observed at the FMR1 locus, and the consequences of the loss of FMRP on human neurodevelopment and neuronal function remain poorly understood. To address these limitations, we report on the generation of induced pluripotent stem cell (iPSC) lines from multiple patients with FXS and the characterization of their differentiation into post-mitotic neurons and glia. We show that clones from reprogrammed FXS patient fibroblast lines exhibit variation with respect to the predominant CGG-repeat length in the FMR1 gene. In two cases, iPSC clones contained predominant CGG-repeat lengths shorter than measured in corresponding input population of fibroblasts. In another instance, reprogramming a mosaic patient having both normal and pre-mutation length CGG repeats resulted in genetically matched iPSC clonal lines differing in FMR1 promoter CpG methylation and FMRP expression. Using this panel of patient-specific, FXS iPSC models, we demonstrate aberrant neuronal differentiation from FXS iPSCs that is directly correlated with epigenetic modification of the FMR1 gene and a loss of FMRP expression. Overall, these findings provide evidence for a key role for FMRP early in human neurodevelopment prior to synaptogenesis and have implications for modeling of FXS using iPSC technology. By revealing disease-associated cellular phenotypes in human neurons, these iPSC models will aid in the discovery of novel therapeutics for FXS and other autism-spectrum disorders sharing common pathophysiology.FRAXA Research FoundationHarvard Stem Cell Institute (seed grant)Stanley Medical Research InstituteNational Institute of Mental Health (U.S.) (grant #R33MH087896