Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab

Background: Pertuzumab, a human epidermal growth factor receptor (HER) 2 dimerization inhibitor, has demonstrated promising efficacy in combination with trastuzumab in patients with metastatic breast cancer. As HER signaling pathways are not only involved in oncogenesis, but also in myocardial homeostasis, an analysis of cardiac safety data was undertaken in a large group of patients treated with pertuzumab. Patients and methods: A complete database of patients treated with full-dose pertuzumab was used to describe the incidence of asymptomatic left ventricular systolic dysfunction (LVSD) and symptomatic heart failure (HF). Results: Information for 598 unique patients was available for the current analysis. Of the patients treated with pertuzumab alone (n = 331) or pertuzumab in combination with a non-anthracycline-containing cytotoxic (n = 175) or trastuzumab (n = 93), 23 (6.9%), 6 (3.4%), and 6 (6.5%), respectively, developed asymptomatic LVSD and 1 (0.3%), 2 (1.1%), and 1 (1.1%), respectively, displayed symptomatic HF. None of the 15 patients receiving both pertuzumab and erlotinib demonstrated LVSD. Conclusions: Patients treated with pertuzumab experienced relatively low levels of asymptomatic LVSD or symptomatic HF. There was no notable increase in cardiac side-effects when pertuzumab was given in combination with other anticancer agent

Single quantum dot states measured by optical modulation spectroscopy

Using optical modulation spectroscopy, we report the direct observation of absorption lines from excitons localized in GaAs single quantum dot potentials. The data provide a measurement of the linewidth, resonance energy, and oscillator strength of the transitions, and show that states which decay primarily by nonradiative processes can be directly probed using this technique. The experiments establish this technique for the characterization of single quantum dot transitions, thereby complementing luminescence studies. © 1999 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70527/2/APPLAB-75-19-2933-1.pd

Culturable Root Endophyte Communities are Shaped by Both Warming and Plant Host Identity in the Rocky Mountains, USA

Understanding the biogeographic patterns of root-associated fungi and their sensitivity to temperature may improve predictions of future changes in terrestrial biodiversity and associated ecosystem processes, but data are currently limited. Anticipating change will require combining observational data, which predict how climatic factors limit current species distributions, with direct manipulations of climate, which can isolate responses to specific climate variables. Root endophytes are common symbionts of plants, particularly in arctic and alpine environments, yet their responses to climate warming are not resolved. Here, we directly cultured endophytic fungi from roots collected along altitudinal gradients in replicated mountain watersheds and from a 27 y field warming experiment in the Rocky Mountains, USA, to improve understanding of climate impacts on fungal root endophytes. Fungal taxa that were common at high elevations declined most under climate warming, whereas low elevation dominants responded neutrally or increased with experimental warming. Altitudinal gradients in fungal communities were strongly specific to the plant host species. Specifically, Poa species had 25–60% greater fungal isolate abundance and 25–38% greater fungal diversity at high elevations than at low elevation sites. In contrast, Festuca thurberi had 64% lower fungal diversity on roots at high elevation than at low elevation. Our results help to improve understanding of the potential for climate change to alter plant-fungal interactions in mountain ecosystems

Demonstration of Universal Parametric Entangling Gates on a Multi-Qubit Lattice

We show that parametric coupling techniques can be used to generate selective entangling interactions for multi-qubit processors. By inducing coherent population exchange between adjacent qubits under frequency modulation, we implement a universal gateset for a linear array of four superconducting qubits. An average process fidelity of $\mathcal{F}=93\%$ is estimated for three two-qubit gates via quantum process tomography. We establish the suitability of these techniques for computation by preparing a four-qubit maximally entangled state and comparing the estimated state fidelity against the expected performance of the individual entangling gates. In addition, we prepare an eight-qubit register in all possible bitstring permutations and monitor the fidelity of a two-qubit gate across one pair of these qubits. Across all such permutations, an average fidelity of $\mathcal{F}=91.6\pm2.6\%$ is observed. These results thus offer a path to a scalable architecture with high selectivity and low crosstalk

What’s Next for Acute Heart Failure Research?

Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED-based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high-priority research areas

The development and growth of the software industry in Ireland: an institutionalized relationship approach

peer-reviewedIreland's software industry emerged in the 1970s and 1980s due to significant international developments and, more importantly, the industrial policy approach adopted in Ireland. The attraction of software foreign direct investment during these decades was followed by the emergence of an internationally competitive Irish software sector. A multitude of factors combine to explain the trajectory of software in Ireland: from developments related to globalization and international trade, to policy makers' efforts to promote an industry where Ireland could forge a comparative advantage internationally. An analysis of industrial dynamics and institutionalized relationships (IRs) furthers our understanding of significant developments in the industry in terms of interactions between firms, government and other stakeholders. This paper makes a novel contribution by analysing Ireland's software industry within the IR framework. The IR approach we employ focuses on the finance IR, the purchase IR, the employment IR, and the commercial IR. The adoption of the IR framework approach is particularly insightful in the Irish case as it facilitates a multifaceted analysis of the complex relationships that have moulded the Irish software industry. Such an approach also facilitates a study of the policy implications and policy prescriptions that are pertinent to the software sector.ACCEPTEDpeer-reviewe

Clinical and Research Considerations for Patients with Hypertensive Acute Heart Failure

Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF

Detecting the influence of initial pioneers on succession at deep-sea vents

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 7 (2012): e50015, doi:10.1371/journal.pone.0050015.Deep-sea hydrothermal vents are subject to major disturbances that alter the physical and chemical environment and eradicate the resident faunal communities. Vent fields are isolated by uninhabitable deep seafloor, so recolonization via dispersal of planktonic larvae is critical for persistence of populations. We monitored colonization near 9°50′N on the East Pacific Rise following a catastrophic eruption in order to address questions of the relative contributions of pioneer colonists and environmental change to variation in species composition, and the role of pioneers at the disturbed site in altering community structure elsewhere in the region. Pioneer colonists included two gastropod species: Ctenopelta porifera, which was new to the vent field, and Lepetodrilus tevnianus, which had been rare before the eruption but persisted in high abundance afterward, delaying and possibly out-competing the ubiquitous pre-eruption congener L. elevatus. A decrease in abundance of C. porifera over time, and the arrival of later species, corresponded to a decrease in vent fluid flow and in the sulfide to temperature ratio. For some species these successional changes were likely due to habitat requirements, but other species persisted (L. tevnianus) or arrived (L. elevatus) in patterns unrelated to their habitat preferences. After two years, disturbed communities had started to resemble pre-eruption ones, but were lower in diversity. When compared to a prior (1991) eruption, the succession of foundation species (tubeworms and mussels) appeared to be delayed, even though habitat chemistry became similar to the pre-eruption state more quickly. Surprisingly, a nearby community that had not been disturbed by the eruption was invaded by the pioneers, possibly after they became established in the disturbed vents. These results indicate that the post-eruption arrival of species from remote locales had a strong and persistent effect on communities at both disturbed and undisturbed vents.The authors received funding from National Science Foundation grant OCE-0424953, WHOI Deep Ocean Exploration Institute, WHOI Summer Student Fellow program, Woods Hole Partnership in Education Program, IFREMER and CNRS, Fondation TOTAL Chair Extreme Marine Environment, Biodiversity and Global change