'Against the World': Michael Field, female marriage and the aura of amateurism'

This article considers the case of Katherine Bradley and Edith Cooper, an aunt and niece who lived and wrote together as ‘Michael Field’ in the fin-de-siècle Aesthetic movement. Bradley’s bold statement that she and Cooper were ‘closer married’ than the Brownings forms the basis for a discussion of their partnership in terms of a ‘female marriage’, a union that is reflected, as I will argue, in the pages of their writings. However, Michael Field’s exclusively collaborative output, though extensive, was no guarantee for success. On the contrary, their case illustrates the notion, valid for most products of co-authorship, that the jointly written work is always surrounded by an aura of amateurism. Since collaboration defied the ingrained notion of the author as the solitary producer of his or her work, critics and readers have time and again attempted to ‘parse’ the collaboration by dissecting the co-authored work into its constituent halves, a treatment that the Fields too failed to escape

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

The Impact of Regulation on Innovation and Choice in Wireless Communications

Proposals to increase regulation of mobile wireless services, for example, by applying net neutrality" regulation, are often based on claims that such regulation would enhance innovation and increase consumer choice. In fact, they would have the opposite effect. The business practices that would be banned by such regulation are efficient mechanisms for spreading and reducing risk, lowering transactions costs, and enhancing marketing activities, all of which contribute to innovation and choice. Moreover, product differentiation increases competition and thus contributes both directly and indirectly to consumer choice. While some types of exclusive agreements and other discriminatory" practices can theoretically harm competition, the precondition for such harm to occur i.e., market power in one or more of the affected markets generally is not present in wireless markets. Hence, the proposed regulations cannot be justified on grounds of market failure. Rather than increasing innovation and consumer choice, as promised, they would severely disrupt the wireless sector's highly successful business model and significantly reduce innovation and consumer choice.

Size-Tuned ZnO Nanocrucible Arrays for Magnetic Nanodot Synthesis <i>via</i> Atomic Layer Deposition-Assisted Block Polymer Lithography

Low-temperature atomic layer deposition of conformal ZnO on a self-assembled block polymer lithographic template comprising well-ordered, vertically aligned cylindrical pores within a poly(styrene) (PS) matrix was used to produce nanocrucible templates with pore diameters tunable <i>via</i> ZnO thickness. Starting from a PS template with a hexagonal array of 30 nm diameter pores on a 45 nm pitch, the ZnO thickness was progressively increased to narrow the pore diameter to as low as 14 nm. Upon removal of the PS by heat treatment in air at 500 °C to form an array of size-tunable ZnO nanocrucibles, permalloy (Ni₈₀Fe₂₀) was evaporated at normal incidence, filling the pores and creating an overlayer. Argon ion beam milling was then used to etch back the overlayer (a Damascene-type process), leaving a well-ordered array of isolated ZnO nanocrucibles filled with permalloy nanodots. Microscopy and temperature-dependent magnetometry verified the diameter reduction with increasing ZnO thickness. The largest diameter (30 nm) dots exhibit a ferromagnetic multidomain/vortex state at 300 K, with relatively weakly temperature-dependent coercivity. Reducing the diameter leads to a crossover to a single-domain state and eventually superparamagnetism at sufficiently high temperature, in quantitative agreement with expectations. We argue that this approach could render this form of block polymer lithography compatible with high-temperature processing (as required for technologically important high perpendicular anisotropy ordered alloys, for instance), in addition to enabling separation-dependent studies to probe interdot magnetostatic interactions

Net neutrality regulation: the economic evidence

In the authors\u27 shared opinion, the economic evidence does not support the regulations proposed in the Commission’s Notice of Proposed Rulemaking Regarding Preserving the Open Internet and Broadband Industry Practices (the “NPRM”). To the contrary, the economic evidence provides no support for the existence of market failure sufficient to warrant ex ante regulation of the type proposed by the Commission, and strongly suggests that the regulations, if adopted, would reduce consumer welfare in both the short and long run. To the extent the types of conduct addressed in the NPRM may, in isolated circumstances, have the potential to harm competition or consumers, the Commission and other regulatory bodies have the ability to deter or prohibit such conduct on a case-by-case basis, through the application of existing doctrines and procedures. Hence, the approach advocated in the NPRM is not necessary to achieve whatever economic benefits may be associated with prohibiting harmful discrimination on the Internet

Defining orellanine as treatment of advanced renal cell carcinoma

Renal cancer causes over 100,000 annual deaths worldwide, and the incidence is increasing. Clear cell renal cell carcinomas (CCRCC), constituting 75% of renal cancer, are known for their high metastatic frequency and resistance to conventional therapies. Metastases are encountered in over half of patients with renal cancer, drastically reducing their life expectancy. Even with new specifically directed molecularly targeted therapies, the median survival of metastasizing CCRCC is less than one year. Orellanine is a nephrotoxin found in fungi, and sometimes ingested accidentally. The ingestion of the fungi leads to renal failure and disruption of the proximal tubular cells. Interestingly, CCRCC originate from this cell type. Our hypothesis is that since proximal tubular cells in the kidney selectively take up orellanine, cancer cells in metastases of the same origin would also do so. This may give rise to a potentially curative therapy against metastasizing CCRCC. The aim of the thesis is to 1) Determine the efficacy of orellanine as a targeted therapy against clear cell renal cell carcinoma in vitro and in vivo 2) Establish a robust technique for detection of orellanine in plasma 3) Evaluate the long-term effects in patients after accidental intake of mushrooms containing orellanine. We could demonstrate that orellanine induces dose-dependent cell death in a number of CCRCC cells while cells from other areas of the body remained unharmed. When we treated human CCRCC xenografts in nude rats with orellanine, the tumor cell mass was significantly reduced within a few days, featuring large apoptotic and necrotic areas. We could also detect orellanine with our newly developed analysis method in minute concentrations. This is necessary for monitoring orellanine concentrations in the body in a possible future clinical trial. The specificity for renal cells was evident in our study of the long-term outcome after accidental intake of orellanine-containing mushrooms. In these patients, we could not detect any difference in mortality or morbidity compared to age- and sex-matched controls. In conclusion, this thesis shows that orellanine is indeed highly toxic to CCRCC cells both in vitro and in vivo. Orellanine seems to be highly kidney-specific with no long-term effects other than renal failure, which can be well dealt with using dialysis or renal transplantation. Orellanine thus has potential to become a new potentially curative treatment of metastatic CCRCC