Human immunodeficiency virus rebound after suppression to < 400 copies/mL during initial highly active antiretroviral therapy regimens, according to prior nucleoside experience and duration of suppression

This study evaluated 1433 human immunodeficiency virus (HIV)-infected patients starting highly active antiretroviral therapy (HAART), 409 (28%) of whom had prior nucleoside experience and achieved an HIV load of <400 copies/mL by 24 weeks of therapy. Three hundred seven patients experienced virus rebound during a total of 2773.3 person-years of follow-up. There was a higher rate of virus rebound among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; 95% confidence interval, 2.22-3.84; P < .0001) and a decreasing rate of virus rebound with increasing duration of virus suppression (i.e., time since achieving a virus load of <400 HIV RNA copies/mL) among both the nucleoside-experienced and naive patients (P < .0001), but the difference between the groups persisted into the third year of follow-up (P = .0007). Even patients who had experienced <2 months of nucleoside therapy before beginning HAART had an increased risk of virus rebound (RH, 1.95; P = .009). It appears that only a small period of pre-HAART nucleoside therapy is sufficient to confer a disadvantage, in terms of risk of virus rebound, that persists for several years

Speciesistic Veganism: An Anthropocentric Argument

The paper proposes an anthropocentric argument for veganism based on a speciesistic premise that most carnists likely affirm: human flourishing should be promoted. I highlight four areas of human suffering promoted by a carnistic diet: (1) health dangers to workers (both physical and psychological), (2) economic dangers to workers, (3) physical dangers to communities around slaughterhouses, and (4) environmental dangers to communities-at-large. Consequently, one could ignore the well-being of non-human animals and nevertheless recognize significant moral failings in the current standard system of meat production

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Whither Capitalism? Financial externalities and crisis

As with global warming, so with financial crises – externalities have a lot to answer for. We look at three of them. First the financial accelerator due to ‘fire sales’ of collateral assets -- a form of pecuniary externality that leads to liquidity being undervalued. Second the ‘risk- shifting’ behaviour of highly-levered financial institutions who keep the upside of risky investment while passing the downside to others thanks to limited liability. Finally, the network externality where the structure of the financial industry helps propagate shocks around the system unless this is checked by some form of circuit breaker, or ‘ring-fence’. The contrast between crisis-induced Great Recession and its aftermath of slow growth in the West and the rapid - and (so far) sustained - growth in the East suggests that successful economic progress may depend on how well these externalities are managed

Theory of Star Formation

We review current understanding of star formation, outlining an overall theoretical framework and the observations that motivate it. A conception of star formation has emerged in which turbulence plays a dual role, both creating overdensities to initiate gravitational contraction or collapse, and countering the effects of gravity in these overdense regions. The key dynamical processes involved in star formation -- turbulence, magnetic fields, and self-gravity -- are highly nonlinear and multidimensional. Physical arguments are used to identify and explain the features and scalings involved in star formation, and results from numerical simulations are used to quantify these effects. We divide star formation into large-scale and small-scale regimes and review each in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and their substructures. Important problems include how GMCs form and evolve, what determines the star formation rate (SFR), and what determines the initial mass function (IMF). Small scales range from dense cores to the protostellar systems they beget. We discuss formation of both low- and high-mass stars, including ongoing accretion. The development of winds and outflows is increasingly well understood, as are the mechanisms governing angular momentum transport in disks. Although outstanding questions remain, the framework is now in place to build a comprehensive theory of star formation that will be tested by the next generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission statement adde

Predator-Induced Vertical Behavior of a Ctenophore

Although many studies have focused on Mnemiopsis leidyi predation, little is known about the role of this ctenophore as prey when abundant in native and invaded pelagic systems. We examined the response of the ctenophore M. leidyi to the predatory ctenophore Beroe ovata in an experiment in which the two species could potentially sense each other while being physically separated. On average, M. leidyi responded to the predator’s presence by increasing variability in swimming speeds and by lowering their vertical distribution. Such behavior may help explain field records of vertical migration, as well as stratified and near-bottom distributions of M. leidyi

Could salvage surgery after chemotherapy have clinical impact on cancer survival of patients with metastatic urothelial carcinoma?

The clinical impact of salvage surgery after chemotherapy on cancer survival of patients with metastatic urothelial carcinoma is controversial. We aimed to verify the clinical role of salvage surgery by analyzing the long-term outcome in patients with urothelial carcinoma treated by chemotherapy. Between 2003 and 2010 at a single institution, 31 of 47 patients (66%) with metastatic urothelial carcinoma showed objective responses (CR in 4, PR in 27) after multiple courses of cisplatin/gemcitabine/paclitaxel-based chemotherapy, and a cohort of patients with partial response (PR) were retrospectively enrolled. Twelve (10 male and 2 female, median age 64.0 years) of 27 patients with PR underwent salvage surgeries after the chemotherapy: metastatectomy of residual lesions (10 retroperitoneal lymph nodes, 2 lung), and 6 radical surgeries for primary lesions as well. Progression-free survival and overall patient survival rates were analyzed retrospectively and compared with those of patients without salvage surgery. All 12 patients achieved surgical CR. Pathological findings of metastatic lesions showed viable cancer cells in 3 patients. In univariate analysis, sole salvage surgery affected overall survival in 27 patients with PR to the chemotherapy (P = 0.0037). Progression-free survival and overall survival rates in patients with salvage surgery were better than those in 15 PR patients without the surgery (39.8 vs. 0%, and 71.6 vs. 12.1% at 3 years, P = 0.01032 and 0.01048; log-rank test). Salvage surgery for patients with residual tumor who achieve partial response to chemotherapy could have a possible impact on cancer survival

The spectra of lifted digraphs

We present a method to derive the complete spectrum of the lift \mathrm{\Gamma\alpha} of a base digraph \mathrm{\Gamma}, with voltage assignment α on a (finite) group $\textit{G}$. The method is based on assigning to \mathrm{\Gamma} a quotient-like matrix whose entries are elements of the group algebra \mathds{C}[$\textit{G}$], which fully represents \mathrm{\Gamma\alpha}. This allows us to derive the eigenvectors and eigenvalues of the lift in terms of those of the base digraph and the irreducible characters of G. Thus, our main theorem generalizes some previous results of Lovász and Babai concerning the spectra of Cayley digraphs