Trastuzumab-associated cardiac events in the Persephone trial

Background:We report cardiac events in the Persephone trial which compares 6–12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. Methods:Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. Results:A total of 2500 patients, aged 22–82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04–1.90)), and not for 6-month patients (OR 1.28 (0.91–1.79)). Conclusions:We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care

Indirect genetic effects clarify how traits can evolve even when fitness does not

Acknowledgmenets We thank Cortland Griswold, Loeske Kruuk, Alastair Wilson, Piter Bijma, Lucas Marie-Orleach, Joel McGlothlin, and an anonymous reviewer for comments and discussions that helped to improve this manuscript. The authors declare no conflicts of interest.Peer reviewedPublisher PD

Two sword lengths apart: Credible commitment problems and physical violence in democratic national legislatures

Ideally, national legislatures in democracies should be venues for peacefully resolving conflicts between opposing groups. However, they can become places of physical violence. Such violence can be an indication that countries’ legislative institutions are functioning far from the democratic ideal of being venues for peaceful conflict reconciliation. In some cases, such as Ukraine prior to the 2014 outbreak of armed conflict in the country’s east and south, violence can indicate and possibly fuel deeper political divisions. In this first global study of legislative violence, I show that brawls are more likely when legislators find it difficult to credibly commit to follow peaceful bargains. Credible commitment problems are more acute in countries with new democracies and disproportionate electoral outcomes – that is, when electoral votes for parties do not closely correspond to the legislative seats they are given. I find robust support for this argument by first examining a case study of legislative violence in the antebellum United States Senate. Pro- and anti-slavery senators became increasingly unable to maintain credible commitments in the lead-up to the 1856 caning of Senator Charles Sumner as the allocation of seats in the legislative body became more disproportional. Second, I find further support for my argument in a new global dataset of contemporary instances of violence in national legislatures. In addition, I find strong evidence that violence is more likely in legislatures with small minority governments. Despite reasonable expectations, civil wars are not associated with more legislative violence

Isotopic and Geochemical Investigation of Two Distinct Mars Analog Environments Using Evolved Gas Techniques in Svalbard, Norway

The 2010 Arctic Mars Analog Svalbard Expedition (AMASE) investigated two distinct geologic settings on Svalbard, using methodologies and techniques to be deployed on Mars Science Laboratory (MSL). AMASErelated research comprises both analyses conducted during the expedition and further analyses of collected samples using laboratory facilities at a variety of institutions. The Sample Analysis at Mars (SAM) instrument suite on MSL includes pyrolysis ovens, a gas-processing manifold, a quadrupole mass spectrometer (QMS), several gas chromatography columns, and a Tunable Laser Spectrometer (TLS). An integral part of SAM development is the deployment of SAM-like instrumentation in the field. During AMASE 2010, two parts of SAM participated as stand-alone instruments. A Hiden Evolved Gas Analysis- Mass Spectrometer (EGA-QMS) system represented the EGA-QMS component of SAM, and a Picarro Cavity Ring Down Spectrometer (EGA-CRDS), represented the EGA-TLS component of SAM. A field analog of CheMin, the XRD/XRF on MSL, was also deployed as part of this field campaign. Carbon isotopic measurements of CO2 evolved during thermal decomposition of carbonates were used together with EGA-QMS geochemical data, mineral composition information and contextual observations made during sample collection to distinguish carbonates formation associated with chemosynthetic activity at a fossil methane seep from abiotic processes forming carbonates associated with subglacial basaltic eruptions. Carbon and oxygen isotopes of the basalt-hosted carbonates suggest cryogenic carbonate formation, though more research is necessary to clarify the history of these rocks

Micromagnetic Investigations of Magnetic Multilayers and Ferrites by Transmission Electron Microscopy

The work described in this thesis is a study of domain structures in Co/Pt multilayers and MnZn-ferrites using Lorentz microscopy. The vast majority of the work is concerned with the multilayers which are produced for use as future magneto-optical media. The basic ideas of ferromagnetism and domain structures together with an outline of the concepts of magneto-optical recording are given in chapter 1. Throughout this thesis, domains are observed using the Foucault, Fresnel and differential phase contrast (DPC) modes of Lorentz microscopy. Chapter 2 explains the techniques used and how they are applied to the materials in question. Also given, is a brief discussion of image formation in a scanning transmission electron microscope (STEM) for DPC imaging which allows induction distributions within thin magnetic films to be mapped. Chapter 3 discusses the deposition and initial characterisation of the multilayers and also reports on the preliminary results achieved from the electron microscopy of these films. Optimum conditions for all the Lorentz modes are given. The main body of results from the Co/Pt multilayers is presented in chapters 4-7. Chapter 4 deals with all the in-situ magnetising results using DPC microscopy. Domain patterns in various remanent states were imaged. Such observations provided great insight into the mechanisms (nucleation and reversal) that determine the shape of the bulk magnetising loop. Remanence loops were constructed from the MDPC images and their shapes agreed well with those measured on the AGFM. An investigation of thermomagnetically written domains (marks) was carried out in chapter 5. Marks written with different parameters were imaged by MDPC and their most important features investigated. It was found that the size of the marks was only weakly dependent on the applied bias field, but increased linearly with increasing laser power. Reverse domains were present in the written mark until the bias field exceeded 30kA.m-1 but above this value the domain boundary became more ragged. A quantitative analysis of the electron signal from a series of marks written with different bias fields was undertaken and the shape of the curve agreed well with actual recording results. In chapter 6 domain wall calculations were carried out and the domain periods modelled for a series of multilayers with increasing numbers of bilayers. The theoretical results agreed best with the experimental measurements when a magnetic characteristic length of 6.7nm was used in the model. Chapter 7 deals with the work carried out during a placement at Philips Research Laboratories. The domain structure of the multilayers was investigated with scanning magnetic force microscopy and the images and results compared with those achieved from Lorentz microscopy. It was found that the greatest spatial resolution and reproducibility was achieved with MDPC microscopy, although SMFM was most useful when imaging written tracks because no specimen preparation was required. Chapter 8 concerns all the work carried out on thinned samples MnZn-ferrite. Domain structures in an ac-demagnetised state were examined for films with different grain sizes. In general it was established that most grains were multidomain. Local variations in the atomic composition across grain boundaries were investigated using energy dispersive x-ray analysis (EDX) and substantial Zn depletion was found in the vicinity of grain boundaries.. Chapter 9 contains conclusions drawn from the observations of chapters 4-8 along with suggestions for the continuation of the work

Exploring mentorship in apprenticeship success: the relationship between construction degree apprentices and their work-based mentors

© Kelly McAdam and David Perrin. This AAM is provided for your own personal use only. It may not be used for resale, reprinting, systematic distribution, emailing, or for any other commercial purpose without the permission of the publisher.Purpose: Degree apprenticeships are becoming more established within the higher education sector, however within England there are growing concerns around the completion rates of apprentices. Whilst there are a number of factors which could be impacting this, the support structure surrounding apprentices throughout their programme is a key consideration. This study aims to investigate the support relationship between construction degree apprentices and their work-based mentors through the lived experiences of both the apprentice and the mentor. Design/methodology/approach: This study adopted a qualitative cross-sectional approach, collecting data from three focus groups involving Level 6 apprentices from a higher education institution and their work-based mentors based in England. The data was analysed inductively using NVivo 12 software to identify codes and key themes. Findings: The relationship between the apprentice and their work-based mentor is key to the success of degree apprenticeships. The data analysis recognised three key themes: knowledge of the apprenticeship process, support structure and employer provider relationship. Originality/value: This study is an original contribution addressing a gap in the literature around higher-level apprentices and their work-based mentors, generating and analysing new primary data, identifying ongoing issues and formulating subsequent recommendations for practice. There are also implications for the current English apprenticeship model and those seeking to adopt or adapt it more widely.Unfunde

4-[(E)-2-Ferrocenylethen­yl]-1,8-naphthalic anhydride

In the structure of the title compound, [Fe(C5H5)(C19H11O3)], the plane of the substituted ferrocene ring is tilted by 14.17 (6)° with respect to the mean plane through the naphthalene ring system. In the crystal structure, centrosymmetric dimers are formed through π–π inter­actions [centroid–centroid distance = 3.624 (2) Å] between the substituted ferrocene ring and the three fused rings of the naphthalic anhydride unit. Pairs of dimers are held together by further naphthalene–naphthalene π–π interactions [distance between parallel mean planes 3.45 (3) Å]. Each dimer inter­acts with four neighbouring dimers in a herringbone fashion through C—H⋯π inter­actions, so forming a two-dimensional sheet-like structure

Sulfur-bearing phases detected by evolved gas analysis of the Rocknest aeolian deposit, Gale Crater, Mars

The Sample Analysis at Mars (SAM) instrument suite detected SO_2, H_(2)S, OCS, and CS_2 from ~450 to 800°C during evolved gas analysis (EGA) of materials from the Rocknest aeolian deposit in Gale Crater, Mars. This was the first detection of evolved sulfur species from a Martian surface sample during in situ EGA. SO_2 (~3–22 µmol) is consistent with the thermal decomposition of Fe sulfates or Ca sulfites, or evolution/desorption from sulfur-bearing amorphous phases. Reactions between reduced sulfur phases such as sulfides and evolved O_2 or H_(2)O in the SAM oven are another candidate SO_2 source. H_(2)S (~41–109 nmol) is consistent with interactions of H_(2)O, H_2 and/or HCl with reduced sulfur phases and/or SO2 in the SAM oven. OCS (~1–5 nmol) and CS2 (~0.2–1 nmol) are likely derived from reactions between carbon-bearing compounds and reduced sulfur. Sulfates and sulfites indicate some aqueous interactions, although not necessarily at the Rocknest site; Fe sulfates imply interaction with acid solutions whereas Ca sulfites can form from acidic to near-neutral solutions. Sulfides in the Rocknest materials suggest input from materials originally deposited in a reducing environment or from detrital sulfides from an igneous source. The presence of sulfides also suggests that the materials have not been extensively altered by oxidative aqueous weathering. The possibility of both reduced and oxidized sulfur compounds in the deposit indicates a nonequilibrium assemblage. Understanding the sulfur mineralogy in Rocknest materials, which exhibit chemical similarities to basaltic fines analyzed elsewhere on Mars, can provide insight in to the origin and alteration history of Martian surface materials

The graduation performance of technology business incubators in China's three tier cities: the role of incubator funding, technical support, and entrepreneurial mentoring

This study examines the effects of technology business incubator (TBI)’s funding, technical support and entrepreneurial mentoring on the graduation performance of new technology-based firms in China’s three tier cities. Using new dataset on all TBIs and incubated new technology-based firms from government surveys conducted over five consecutive years from 2009 to 2013 combined with archival and hand-collected data, we find the effects of incubator services on the early growth of new technology-based firms vary according to the local context. Technical support facilities and entrepreneurial mentoring from TBIs are found to have significantly and positively influenced the early development of the firms in the four most affluent tier 1 cities, whilst these effects become less pronounced for the tier 2 and tier 3 cities. These two services are also found to influence graduation performance in the government and university types of TBI respectively. Results support the notion that the effectiveness of an incubators services is shaped by the level of a city’s socio-economic development and that the city location of a TBI does impact the graduation performance of its incubatees