Are Regulation and Innovation Priorities Serving Public Health Needs?

A host of challenges confront healthcare authorities worldwide. Topping the list is the demand for innovative new medicines to treat a range of both infectious and non-communicable diseases, while containing spiraling healthcare costs. The challenge is particularly great in therapeutic areas where, despite significant medical need and economic impact, the technical challenges and commercial risk of development serve as disincentives to drug sponsors. These areas include cardiovascular diseases as well as diseases and disorders of the central nervous system. Currently, the development and approval of new active substances, with its disproportionate focus on oncology, is not in alignment with healthcare needs in most geographic regions. In this article, we discuss the origins of this misalignment and suggest various approaches to address healthcare needs going forward

Directly observing squeezed phonon states with femtosecond x-ray diffraction

Squeezed states are quantum states of a harmonic oscillator in which the variance of two conjugate variables each oscillate out of phase. Ultrafast optical excitation of crystals can create squeezed phonon states, where the variance of the atomic displacements oscillates due to a sudden change in the interatomic bonding strength. With femtosecond x-ray diffraction we measure squeezing oscillations in bismuth and conclude that they are consistent with a model in which electronic excitation softens all phonon modes by a constant scaling factor

Multi-Epoch Spectropolarimetry for a Sample of Type IIn Supernovae: Persistent Asymmetry in Dusty Circumstellar Material

We present multi-epoch spectropolarimetry and spectra for a sample of 14 Type IIn supernovae (SNe IIn). We find that after correcting for likely interstellar polarization, SNe IIn commonly show intrinsic continuum polarization of 1--3% at the time of peak optical luminosity, although a few show weaker or negligible polarization. While some SNe IIn have even stronger polarization at early times, their polarization tends to drop smoothly over several hundred days after peak. We find a tendency for the intrinsic polarization to be stronger at bluer wavelengths, especially at early times. While polarization from an electron scattering region is expected to be grey, scattering of SN light by dusty circumstellar material (CSM) may induce such a wavelength-dependent polarization. For most SNe IIn, changes in polarization degree and wavelength dependence are not accompanied by changes in the position angle, requiring that asymmetric pre-SN mass loss had a persistent geometry. While 2--3% polarization is typical, about 30% of SNe IIn have very low or undetected polarization. Under the simplifying assumption that all SN IIn progenitors have axisymmetric CSM (i.e. disk/torus/bipolar), then the distribution of polarization values we observe is consistent with similarly asymmetric CSM seen from a distribution of random viewing angles. This asymmetry has very important implications for understanding the origin of pre-SN mass loss in SNe IIn, suggesting that it was shaped by binary interaction.Comment: 76 pages, 54 figures (13 in main text, 41 in appendix A

SN2012ab: A Peculiar Type IIn Supernova with Aspherical Circumstellar Material

We present photometry, spectra, and spectropolarimetry of supernova (SN) 2012ab, mostly obtained over the course of $\sim 300$ days after discovery. SN 2012ab was a Type IIn (SN IIn) event discovered near the nucleus of spiral galaxy 2MASXJ12224762+0536247. While its light curve resembles that of SN 1998S, its spectral evolution does not. We see indications of CSM interaction in the strong intermediate-width emission features, the high luminosity (peak at absolute magnitude $M=-19.5$), and the lack of broad absorption features in the spectrum. The H$\alpha$ emission undergoes a peculiar transition. At early times it shows a broad blue emission wing out to $-14{,}000$ km $\mathrm{s^{-1}}$ and a truncated red wing. Then at late times ($>$ 100$\,$days) it shows a truncated blue wing and a very broad red emission wing out to roughly $+20{,}000$ km $\mathrm{s^{-1}}$. This late-time broad red wing probably arises in the reverse shock. Spectra also show an asymmetric intermediate-width H$\alpha$ component with stronger emission on the red side at late times. The evolution of the asymmetric profiles requires a density structure in the distant CSM that is highly aspherical. Our spectropolarimetric data also suggest asphericity with a strong continuum polarization of $\sim 1-3$% and depolarization in the H$\alpha$ line, indicating asphericity in the CSM at a level comparable to that in other SNe IIn. We estimate a mass-loss rate of $\dot{M} = 0.050\, {\rm M}_{\odot}\,\mathrm{yr^{-1}}$ for $v_{\rm pre} = 100$$\,$km$\,$$\mathrm{s^{-1}}$ extending back at least 75$\,$yr prior to the SN. The strong departure from axisymmetry in the CSM of SN 2012ab may suggest that the progenitor was an eccentric binary system undergoing eruptive mass loss.Comment: 18 pages, 12 figure

ClassifyMe: A Field-Scouting Software for the Identification of Wildlife in Camera Trap Images

We present ClassifyMe a software tool for the automated identification of animal species from camera trap images. ClassifyMe is intended to be used by ecologists both in the field and in the office. Users can download a pre-trained model specific to their location of interest and then upload the images from a camera trap to a laptop or workstation. ClassifyMe will identify animals and other objects (e.g., vehicles) in images, provide a report file with the most likely species detections, and automatically sort the images into sub-folders corresponding to these species categories. False Triggers (no visible object present) will also be filtered and sorted. Importantly, the ClassifyMe software operates on the user's local machine (own laptop or workstation) - not via internet connection. This allows users access to state-of-the-art camera trap computer vision software in situ, rather than only in the office. The software also incurs minimal cost on the end-user as there is no need for expensive data uploads to cloud services. Furthermore, processing the images locally on the users' end-device allows them data control and resolves privacy issues surrounding transfer and third-party access to users' datasets

SN 2014ab: An Aspherical Type IIn Supernova with Low Polarization

We present photometry, spectra, and spectropolarimetry of supernova (SN) 2014ab, obtained through $\sim 200$ days after peak brightness. SN 2014ab was a luminous Type IIn SN ($M_V < -19.14$ mag) discovered after peak brightness near the nucleus of its host galaxy, VV 306c. Prediscovery upper limits constrain the time of explosion to within 200 days prior to discovery. While SN 2014ab declined by $\sim 1$ mag over the course of our observations, the observed spectrum remained remarkably unchanged. Spectra exhibit an asymmetric emission-line profile with a consistently stronger blueshifted component, suggesting the presence of dust or a lack of symmetry between the far side and near side of the SN. The Pa$\beta$ emission line shows a profile very similar to that of H$\alpha$, implying that this stronger blueshifted component is caused either through obscuration by large dust grains, occultation by optically thick material, or a lack of symmetry between the far side and near side of the interaction region. Despite these asymmetric line profiles, our spectropolarimetric data show that SN 2014ab has little detected polarization after accounting for the interstellar polarization. This suggests that we are seeing emission from a photosphere that has only small deviation from circular symmetry face-on. We are likely seeing a SN IIn with nearly circular symmetry in the plane normal to our line of sight, but with either large-grain dust or significant asymmetry in the density of circumstellar material or SN ejecta along our line of sight. We suggest that SN 2014ab and SN 2010jl (as well as other SNe IIn) may be similar events viewed from different directions.Comment: 20 pages, 19 figure

Vero Cytotoxin–Producing Escherichia coli O157 Gastroenteritis in Farm Visitors, North Wales

An outbreak of Vero cytotoxin–producing Escherichia coli O157 (VTEC O157) gastroenteritis in visitors to an open farm in North Wales resulted in 17 primary and 7 secondary cases of illness. E. coli O157 Vero cytotoxin type 2, phage type 2 was isolated from 23 human cases and environmental animal fecal samples. A case-control study of 16 primary case-patients and 36 controls (all children) showed a significant association with attendance on the 2nd day of a festival, eating ice cream or cotton candy (candy floss), and contact with cows or goats. On multivariable analysis, only the association between illness and ice cream (odds ratio [OR]=11.99, 95% confidence interval [CI] 1.04 to 137.76) and cotton candy (OR=51.90, 95% CI 2.77 to 970.67) remained significant. In addition to supervised handwashing, we recommend that foods on open farms only be eaten in dedicated clean areas and that sticky foods be discouraged

A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density.

INTRODUCTION: Mammographic density is an established breast cancer risk factor with a strong genetic component and can be increased in women using menopausal hormone therapy (MHT). Here, we aimed to identify genetic variants that may modify the association between MHT use and mammographic density. METHODS: The study comprised 6,298 postmenopausal women from the Mayo Mammography Health Study and nine studies included in the Breast Cancer Association Consortium. We selected for evaluation 1327 single nucleotide polymorphisms (SNPs) showing the lowest P-values for interaction (P int) in a meta-analysis of genome-wide gene-environment interaction studies with MHT use on risk of breast cancer, 2541 SNPs in candidate genes (AKR1C4, CYP1A1-CYP1A2, CYP1B1, ESR2, PPARG, PRL, SULT1A1-SULT1A2 and TNF) and ten SNPs (AREG-rs10034692, PRDM6-rs186749, ESR1-rs12665607, ZNF365-rs10995190, 8p11.23-rs7816345, LSP1-rs3817198, IGF1-rs703556, 12q24-rs1265507, TMEM184B-rs7289126, and SGSM3-rs17001868) associated with mammographic density in genome-wide studies. We used multiple linear regression models adjusted for potential confounders to evaluate interactions between SNPs and current use of MHT on mammographic density. RESULTS: No significant interactions were identified after adjustment for multiple testing. The strongest SNP-MHT interaction (unadjusted P int <0.0004) was observed with rs9358531 6.5kb 5' of PRL. Furthermore, three SNPs in PLCG2 that had previously been shown to modify the association of MHT use with breast cancer risk were found to modify also the association of MHT use with mammographic density (unadjusted P int <0.002), but solely among cases (unadjusted P int SNP×MHT×case-status <0.02). CONCLUSIONS: The study identified potential interactions on mammographic density between current use of MHT and SNPs near PRL and in PLCG2, which require confirmation. Given the moderate size of the interactions observed, larger studies are needed to identify genetic modifiers of the association of MHT use with mammographic density.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-015-0625-

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis