Dissipative and Dispersive Optomechanics in a Nanocavity Torque Sensor

Dissipative and dispersive optomechanical couplings are experimentally observed in a photonic crystal split-beam nanocavity optimized for detecting nanoscale sources of torque. Dissipative coupling of up to approximately $500$ MHz/nm and dispersive coupling of $2$ GHz/nm enable measurements of sub-pg torsional and cantilever-like mechanical resonances with a thermally-limited torque detection sensitivity of 1.2$\times 10^{-20} \text{N} \, \text{m}/\sqrt{\text{Hz}}$ in ambient conditions and 1.3$\times 10^{-21} \text{N} \, \text{m}/\sqrt{\text{Hz}}$ in low vacuum. Interference between optomechanical coupling mechanisms is observed to enhance detection sensitivity and generate a mechanical-mode-dependent optomechanical wavelength response.Comment: 11 pages, 6 figure

Designing Pleasure; Designers' Needs

A series of interviews with academic and practicing designers was carried out to inform the development of a ‘pleasure resource’ that designers can use to enable understanding of the emotional needs of specific markets, at an early stage of the design process. In order to produce such a resource, it was necessary to investigate the attitudes and needs of designers on the subject of ‘pleasure’ in design. Findings show that designers are aware of the necessity to satisfy the emotional needs of the user, but there has to be a compromise with other factors e.g. production costs. Those interviewed tended to rely upon ‘quick and dirty’ research methods, with few aware of techniques and data that relate specifically to user pleasure. They expressed great interest in a ‘pleasure resource’ that gave them access to information about specific market groups’ emotional needs. Several designers suggested a greater focus on user ‘lifestyle’ information to promote empathy with users. The information collected has led to the development of several concept resources for detailed evaluation by designers

Comparison of the Host Ranges and Antigenicity of Cryptosporidium parvum and Cryptosporidium wrairi from Guinea Pigs

Oocysts of a Cryptosporidium isolate from guinea pigs were not infectious for adult mice, but were infectious for two of three newborn calves and for suckling mice. However, oocysts isolated from calves or mice infected with guinea pig Cryptosporidium were not infectious for guinea pigs. Four isolates of C. parvum from calves were incapable of infecting weanling guinea pigs. Microscopic examination of tissue from the colon and cecum of suckling guinea pigs inoculated with C. parvum revealed sparse infection of some pups. These host range studies and previously described differences in 125 I-labeled oocyst surface protein profiles between Cryptosporidium sp. from guinea pigs and C. parvum suggest they are distinct species. We propose the name Cryptosporidium wrairi be retained. Studies with monoclonal antibodies indicate that C. wrairi and C. parvum are antigenically related.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75184/1/j.1550-7408.1992.tb01471.x.pd

Role of hyperpolarization-activated cyclic nucleotide-gated ion channels in neuropathic pain: a proof-of-concept study of ivabradine in patients with chronic peripheral neuropathic pain.

INTRODUCTION: Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels mediate repetitive action potential firing in the heart and nervous system. The HCN2 isoform is expressed in nociceptors, and preclinical studies suggest a critical role in neuropathic pain. Ivabradine is a nonselective HCN blocker currently available for prescription for cardiac indications. Mouse data suggest that ivabradine in high concentrations is equianalgesic with gabapentin. We sought to translate these findings to patients with chronic peripheral neuropathic pain. OBJECTIVES: We sought to translate these findings to patients with chronic peripheral neuropathic pain. METHODS: We adopted an open-label design, administering increasing doses of ivabradine to target a heart rate of 50 to 60 BPM, up to a maximum of 7.5 mg twice daily. All participants scored their pain on an 11-point numerical rating scale (NRS). RESULTS: Seven (7) participants received the drug and completed the study. There was no significant treatment effect on the primary endpoint, the difference between the mean score at baseline and at maximum dosing (mean reduction = 0.878, 95% CI = -2.07 to 0.31, P = 0.1). Exploratory analysis using linear mixed models, however, revealed a highly significant correlation between ivabradine dose and pain scores (χ2(1) = 74.6, P < 0.001), with a reduction of 0.12 ± 0.01 (SEM) NRS points per milligram. The 2 participants with painful diabetic neuropathy responded particularly well. CONCLUSION: This suggests that ivabradine may be efficacious at higher doses, particularly in patients with diabetic neuropathic pain. Importantly, participants reported no adverse effects. These data suggest that ivabradine, a peripherally restricted drug (devoid of central nervous system side effects), is well tolerated in patients with chronic neuropathic pain. Ivabradine is now off-patent, and its analgesic potential merits further investigation in clinical trials.This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The authors acknowledge support from the East of England NIHR Clinical Research Network who facilitated identification of participants, and the staff at the Cambridge NIHR Clinical Investigation Ward, who cared for our participants during their visit. The authors are grateful to Mr Abhishek Dixit who built and maintained OpenClinica for data capture. The in-house development and use of FAST-diary are supported by Evelyn Trust (RECORD-Pain) and AAGBI (Anaesthesia-Wiley) research grants

Blazars in the Fermi Era: The OVRO 40-m Telescope Monitoring Program

The Large Area Telescope (LAT) aboard the Fermi Gamma-ray Space Telescope provides an unprecedented opportunity to study gamma-ray blazars. To capitalize on this opportunity, beginning in late 2007, about a year before the start of LAT science operations, we began a large-scale, fast-cadence 15 GHz radio monitoring program with the 40-m telescope at the Owens Valley Radio Observatory (OVRO). This program began with the 1158 northern (declination>-20 deg) sources from the Candidate Gamma-ray Blazar Survey (CGRaBS) and now encompasses over 1500 sources, each observed twice per week with a ~4 mJy (minimum) and 3% (typical) uncertainty. Here, we describe this monitoring program and our methods, and present radio light curves from the first two years (2008 and 2009). As a first application, we combine these data with a novel measure of light curve variability amplitude, the intrinsic modulation index, through a likelihood analysis to examine the variability properties of subpopulations of our sample. We demonstrate that, with high significance (7-sigma), gamma-ray-loud blazars detected by the LAT during its first 11 months of operation vary with about a factor of two greater amplitude than do the gamma-ray-quiet blazars in our sample. We also find a significant (3-sigma) difference between variability amplitude in BL Lacertae objects and flat-spectrum radio quasars (FSRQs), with the former exhibiting larger variability amplitudes. Finally, low-redshift (z<1) FSRQs are found to vary more strongly than high-redshift FSRQs, with 3-sigma significance. These findings represent an important step toward understanding why some blazars emit gamma-rays while others, with apparently similar properties, remain silent.Comment: 23 pages, 24 figures. Submitted to ApJ

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Mapping policies and programmes: the use of GIS to communicate spatial relationships in England

It has long been acknowledged that there is a gap between the advancement of GIS in the research field and its application in planning practice. This paper demonstrates the potential for employing simple GIS mapping overlays as a way of communicating complex planning issues in a ‘language’ that is easily understandable and effective at stimulating policy debate, critical thinking and learning. The analysis focuses on capturing the synergies and conflicts in two key planning challenges in England, progrowth and housing delivery agendas. In a political context where spatial evidencebased policymaking has been eroded in recent years, the analysis demonstrates the need for policymakers to ‘think spatially, act spatially’ when developing different policies and programmes. The paper concludes that only by making spatial relationships of policies and programmes explicit in a manner that is easily understood by a range of actors, can different spatial scenarios and metaphors of future opportunities and challenges be developed to inform long-range development and planning

Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group

Chemotherapy with alternating vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide cycles and primary tumor treatment with surgery and/or radiation therapy constitute the usual approach to localized Ewing sarcoma in North America. We tested whether chemotherapy intensification through interval compression could improve outcome