Identification of fetal DNA and cells in skin lesions from women with systemic sclerosis

BACKGROUND: Systemic sclerosis is a disease of unknown origin which often occurs in women after their childbearing years. It has many clinical and histopathological similarities to chronic graft-versus-host disease. Recent studies indicate that fetal stem cells can survive in the maternal circulation for many years post partum. This finding suggests that fetal cells persisting in the maternal circulation or tissues could be involved in the pathogenesis of systemic sclerosis by initiating a graft-versus-host reaction. METHODS: We used the polymerase chain reaction (PCR) to identify Y-chromosome sequences in DNA extracted from peripheral-blood cells and skin lesions from women with systemic sclerosis of recent onset. To confirm the PCR findings, we used fluorescence in situ hybridization of peripheral-blood cells and cells within chronic inflammatory-cell infiltrates in biopsy specimens of affected skin. RESULTS: Y-chromosome sequences were found in DNA from peripheral-blood cells in 32 of 69 women with systemic sclerosis (46 percent), as compared with 1 of 25 normal women (4 percent, P\u3c0.001), and in T lymphocytes from 3 women with systemic sclerosis who had male offspring. Furthermore, Y-chromosome sequences were identified in skin-biopsy specimens from 11 of 19 women with systemic sclerosis (58 percent); 9 of the 11 were known to have carried male fetuses. Nucleated cells containing Y chromosomes were detected by fluorescence in situ hybridization in paraffin-embedded sections of skin lesions from all seven women we tested whose skin-biopsy specimens contained Y-chromosome sequences. CONCLUSIONS: Fetal antimaternal graft-versus-host reactions may be involved in the pathogenesis of systemic sclerosis in some women

Stimulated emission of polarization-entangled photons

Entangled photon pairs -- discrete light quanta that exhibit non-classical correlations -- play a crucial role in quantum information science (for example in demonstrations of quantum non-locality and quantum cryptography). At the macroscopic optical field level non-classical correlations can also be important, as in the case of squeezed light, entangled light beams and teleportation of continuous quantum variables. Here we use stimulated parametric down-conversion to study entangled states of light that bridge the gap between discrete and macroscopic optical quantum correlations. We demonstrate experimentally the onset of laser-like action for entangled photons. This entanglement structure holds great promise in quantum information science where there is a strong demand for entangled states of increasing complexity.Comment: 5 pages, 4 figures, RevTeX

Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer

OBJECTIVE: Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-cancer gene therapy, in combination with paclitaxel in patients with platinum resistant ovarian cancer (PROC). METHODS: The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. RESULTS: The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. CONCLUSIONS: At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified

Can a falling tree make a noise in two forests at the same time?

It is a commonplace to claim that quantum mechanics supports the old idea that a tree falling in a forest makes no sound unless there is a listener present. In fact, this conclusion is far from obvious. Furthermore, if a tunnelling particle is observed in the barrier region, it collapses to a state in which it is no longer tunnelling. Does this imply that while tunnelling, the particle can not have any physical effects? I argue that this is not the case, and moreover, speculate that it may be possible for a particle to have effects on two spacelike separate apparatuses simultaneously. I discuss the measurable consequences of such a feat, and speculate about possible statistical tests which could distinguish this view of quantum mechanics from a ``corpuscular'' one. Brief remarks are made about an experiment underway at Toronto to investigate these issues.Comment: 9 pp, Latex, 3 figs, to appear in Proc. Obsc. Unr. Conf.; Fig 2 postscript repaired on 26.10.9

Thermodynamics of Large N Gauge Theories with Chemical Potentials in a 1/D Expansion

In order to understand thermodynamical properties of N D-branes with chemical potentials associated with R-symmetry charges, we study a one dimensional large N gauge theory (bosonic BFSS type model) as a first step. This model is obtained through a dimensional reduction of a 1+D dimensional SU(N) Yang-Mills theory and we use a 1/D expansion to investigate the phase structure. We find three phases in the \mu-T plane. We also show that all the adjoint scalars condense at large D and obtain a mass dynamically. This dynamical mass protects our model from the usual perturbative instability of massless scalars in a non-zero chemical potential. We find that the system is at least meta-stable for arbitrary large values of the chemical potentials in D \to \infty limit. We also explore the existence of similar condensation in higher dimensional gauge theories in a high temperature limit. In 2 and 3 dimensions, the condensation always happens as in one dimensional case. On the other hand, if the dimension is higher than 4, there is a critical chemical potential and the condensation happens only if the chemical potentials are below it.Comment: 37 pages, 4 figures; v2: minor corrections, references added; v3: minor corrections, to appear in JHE

Chest pain with ST segment elevation in a patient with prosthetic aortic valve infective endocarditis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute ST-segment elevation myocardial infarction secondary to atherosclerotic plaque rupture is a common medical emergency. This condition is effectively managed with percutaneous coronary intervention or thrombolysis. We report a rare case of acute myocardial infarction secondary to coronary embolisation of valvular vegetation in a patient with infective endocarditis, and we highlight how the management of this phenomenon may not be the same.</p> <p>Case presentation</p> <p>A 73-year-old British Caucasian man with previous tissue aortic valve replacement was diagnosed with and treated for infective endocarditis of his native mitral valve. His condition deteriorated in hospital and repeat echocardiography revealed migration of vegetation to his aortic valve. Whilst waiting for surgery, our patient developed severe central crushing chest pain with associated anterior ST segment elevation on his electrocardiogram. Our patient had no history or risk factors for ischaemic heart disease. It was likely that coronary embolisation of part of the vegetation had occurred. Thrombolysis or percutaneous coronary intervention treatments were not performed in this setting and a plan was made for urgent surgical intervention. However, our patient deteriorated rapidly and unfortunately died.</p> <p>Conclusion</p> <p>Clinicians need to be aware that atherosclerotic plaque rupture is not the only cause of acute myocardial infarction. In the case of septic vegetation embolisation, case report evidence reveals that adopting the current strategies used in the treatment of myocardial infarction can be dangerous. Thrombolysis risks intra-cerebral hemorrhage from mycotic aneurysm rupture. Percutaneous coronary intervention risks coronary mycotic aneurysm formation, stent infections as well as distal septic embolisation. As yet, there remains no defined treatment modality and we feel all cases should be referred to specialist cardiac centers to consider how best to proceed.</p

Heavy quark density in N=4 SYM: from hedgehog to Lifshitz spacetimes

We study the effect of an order N^2 density of heavy quarks in strongly coupled N=4 SUSY Yang-Mills theory in the large N limit. This is achieved in the type IIB supergravity dual by introducing a uniformly smeared density of macroscopic string sources stretching to the boundary of AdS_5 x S^5. The backreacted system exhibits a flow from an AdS_5 "hedgehog" geometry to a scaling Lifshitz-like solution Lif_5 x S^5 with dynamical critical exponent z=7, wherein the scaling symmetry is broken by a logarithmic running dilaton. We find an exact black brane solution within the scaling regime which describes the low temperature thermodynamics of the system.Comment: 20 pages, 2 figures, references adde

Assessment of correlation between knee notch width index and the three-dimensional notch volume

This study was done to determine whether there is a correlation between the notch volume and the notch width index (NWI) as measured on the three most frequently used radiographic views: the Holmblad 45°, Holmblad 70°, and Rosenberg view. The notch volume of 20 cadaveric knees was measured using Computed Tomography (CT). The Holmblad 45°, Holmblad 70°, and Rosenberg notch view radiographs were digitally re-created from the CT scans for each specimen, and the NWI was measured by two observers. The Pearson correlation coefficient between the NWI and notch volume was calculated, as well as between the three views. An independent t test was performed to determine the difference in NWI and notch volume between male and female specimens. The reliability for each view was also determined. There was no correlation between the NWI as measured on the Holmblad 45°, Holmblad 70°, or Rosenberg view and the notch volume. All three radiographic views proved reliable, but showed only a moderate correlation with each other. Men had larger notch volumes than women, but there was no difference in NWI. A knee with a small intercondylar notch is often considered an increased risk for ACL rupture. The NWI is a frequently used two-dimensional method to determine notch size. However, in the present study, this index was not positively correlated with the overall volume of the notch. Based on the results of the current study, the authors would advice to use caution when using notch view radiographs in a clinical setting to predict risk of ACL rupture

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Predictors of inhospital mortality and re-hospitalization in older adults with community-acquired pneumonia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>A better understanding of potentially modifiable predictors of in-hospital mortality and re-admission to the hospital following discharge may help to improve management of community-acquired pneumonia in older adults. We aimed to assess the associations of potentially modifiable factors with mortality and re-hospitalization in older adults hospitalized with community-acquired pneumonia.</p> <p>Methods</p> <p>A prospective cohort study was conducted from July 2003 to April 2005 in two Canadian cities. Patients aged 65 years or older hospitalized for community-acquired pneumonia were followed up for up to 30 days from initial hospitalization for mortality and these patients who were discharged alive within 30 days of initial hospitalization were followed up to 90 days of initial hospitalization for re-hospitalization. Separate logistic regression analyses were performed identify the predictors of mortality and re-hospitalization.</p> <p>Results</p> <p>Of 717 enrolled patients hospitalized for community-acquired pneumonia, 49 (6.8%) died within 30 days of hospital admission. Among these patients, 526 were discharged alive within 30 days of hospitalization of whom 58 (11.2%) were re-hospitalized within 90 days of initial hospitalization. History of hip fracture (odds ratio (OR) = 4.00, 95% confidence interval (CI) = (1.46, 10.96), P = .007), chronic obstructive pulmonary disease (OR = 2.31, 95% CI = (1.18, 4.50), P = .014), cerebrovascular disease (OR = 2.11, 95% CI = (1.03, 4.31), P = .040) were associated with mortality. Male sex (OR = 2.35, 95% CI = (1.13, 4.85), P = .022) was associated with re-hospitalization while vitamin E supplementation was protective (OR = 0.37 (0.16, 0.90), P = .028). Lower socioeconomic status, prior influenza and pneumococcal vaccinations, appropriate antibiotic prescription upon admission, and lower nutrition risk were not significantly associated with mortality or re-hospitalization.</p> <p>Conclusion</p> <p>Chronic comorbidities appear to be the most important predictors of death and re-hospitalization in older adults hospitalized with community-acquired pneumonia while vitamin E supplementation was protective.</p