Investigating investment in biopharmaceutical R&D

Recent studies have highlighted a reduction in projected financial returns associated with biopharmaceutical R&D, owing to decreased productivity, increases in costs and flattening revenue per new drug, prompting calls for dramatic revisions to R&D models. On the basis of previous financial modelling, the simplest hypothesis would be that new investment in such R&D should be minimal and focused on biologics in preference to small molecules, as the internal rate of return on investment for biologics projects has been reported to be higher (Nat. Rev. Drug Discov. 8, 609–610; 2009). We sought to discern how investors have been acting in recent years, and so examined investment trends in nascent public biopharmaceutical companies located in the United States by constructing a database of such companies that had US initial public offerings (IPOs) between 2010 and 2014 (see Supplementary information S1 (box) for details). We then analysed the characteristics of the 113 companies that met our inclusion criteria, including their corporate strategy and therapeutic modality focus. Here, we present the key findings from this analysis and discuss its implications based on our own financial modelling.United States. National Institutes of Health (NIANIH/R01AG043560

Chronicles of Oklahoma

Article depicts the period of time Will Rogers, "Oklahoma's Favorite Son", spent performing in a Wild West Show in South Africa and how his experiences there impacted his future career

A Survey of Merger Remnants II: The Emerging Kinematic and Photometric Correlations

This paper is the second in a series exploring the properties of 51 {\it optically} selected, single-nuclei merger remnants. Spectroscopic data have been obtained for a sub-sample of 38 mergers and combined with previously obtained infrared photometry to test whether mergers exhibit the same correlations as elliptical galaxies among parameters such as stellar luminosity and distribution, central stellar velocity dispersion ($\sigma$$_{\circ}$), and metallicity. Paramount to the study is to test whether mergers lie on the Fundamental Plane. Measurements of $\sigma$$_{\circ}$ have been made using the Ca triplet absorption line at 8500 {\AA} for all 38 mergers in the sub-sample. Additional measurements of $\sigma$$_{\circ}$ were made for two of the mergers in the sub-sample using the CO absorption line at 2.29 \micron. The results indicate that mergers show a strong correlation among the parameters of the Fundamental Plane but fail to show a strong correlation between $\sigma$$_{\circ}$ and metallicity (Mg$_{2}$). In contrast to earlier studies, the $\sigma$$_{\circ}$ of the mergers are consistent with objects which lie somewhere between intermediate-mass and luminous giant elliptical galaxies. However, the discrepancies with earlier studies appears to correlate with whether the Ca triplet or CO absorption lines are used to derive $\sigma$$_{\circ}$, with the latter almost always producing smaller values. Finally, the photometric and kinematic data are used to demonstrate for the first time that the central phase-space density of mergers are equivalent to elliptical galaxies. This resolves a long-standing criticism of the merger hypothesis.Comment: Accepted Astronomical Journal (to appear in January 2006

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells.

Repurposed CRISPR-Cas molecules provide a useful tool set for broad applications of genomic editing and regulation of gene expression in prokaryotes and eukaryotes. Recent discovery of phage-derived proteins, anti-CRISPRs, which serve to abrogate natural CRISPR anti-phage activity, potentially expands the ability to build synthetic CRISPR-mediated circuits. Here, we characterize a panel of anti-CRISPR molecules for expanded applications to counteract CRISPR-mediated gene activation and repression of reporter and endogenous genes in various cell types. We demonstrate that cells pre-engineered with anti-CRISPR molecules become resistant to gene editing, thus providing a means to generate "write-protected" cells that prevent future gene editing. We further show that anti-CRISPRs can be used to control CRISPR-based gene regulation circuits, including implementation of a pulse generator circuit in mammalian cells. Our work suggests that anti-CRISPR proteins should serve as widely applicable tools for synthetic systems regulating the behavior of eukaryotic cells

Modelling galactic spectra: I - A dynamical model for NGC3258

In this paper we present a method to analyse absorption line spectra of a galaxy designed to determine the stellar dynamics and the stellar populations by a direct fit to the spectra. This paper is the first one to report on the application of the method to data. The modelling results in the knowledge of distribution functions that are sums of basis functions. The practical implementation of the method is discussed and a new type of basis functions is introduced. With this method, a dynamical model for NGC 3258 is constructed. This galaxy can be successfully modelled with a potential containing 30% dark matter within 1r_e with a mass of 1.6x10^11 M_o. The total mass within 2r_e is estimated as 5x10^11 M_o, containing 63% dark matter. The model is isotropic in the centre, is radially anisotropic between 0.2 and 2 kpc (0.88 r_e) and becomes tangentially anisotropic further on. The photometry reveals the presence of a dust disk near the centre

Torsion and vibration-torsion levels of the S1 and ground cation electronic states of para-fluorotoluene

We investigate the low-energy transitions (0–570 cm-1) of the S1 state of para-fluorotoluene (pFT) using a combination of resonance-enhanced multiphoton ionization (REMPI) and zero-kinetic-energy (ZEKE) spectroscopy and quantum chemical calculations. By using various S1 states as intermediate levels, we obtain zero-kinetic-energy (ZEKE) spectra. The differing activity observed allows detailed assignments to be made of both the cation and S1 low-energy levels. The assignments are in line with the recently-published work on toluene from the Lawrance group [J. Chem. Phys. 143, 044313 (2015)], which considered vibration-torsion coupling in depth for the S1 state of toluene. In addition, we investigate whether two bands that occur in the range 390–420 cm-1 are the result of a Fermi resonance; we present evidence for weak coupling between various vibrations and torsions that contribute to this region. This work has led to the identification of a number of misassignments in the literature, and these are corrected

A Comparative Study of the ReCell® Device and Autologous Spit-Thickness Meshed Skin Graft in the Treatment of Acute Burn Injuries.

Early excision and autografting are standard care for deeper burns. However, donor sites are a source of significant morbidity. To address this, the ReCell® Autologous Cell Harvesting Device (ReCell) was designed for use at the point-of-care to prepare a noncultured, autologous skin cell suspension (ASCS) capable of epidermal regeneration using minimal donor skin. A prospective study was conducted to evaluate the clinical performance of ReCell vs meshed split-thickness skin grafts (STSG, Control) for the treatment of deep partial-thickness burns. Effectiveness measures were assessed to 1 year for both ASCS and Control treatment sites and donor sites, including the incidence of healing, scarring, and pain. At 4 weeks, 98% of the ASCS-treated sites were healed compared with 100% of the Controls. Pain and assessments of scarring at the treatment sites were reported to be similar between groups. Significant differences were observed between ReCell and Control donor sites. The mean ReCell donor area was approximately 40 times smaller than that of the Control (P < .0001), and after 1 week, significantly more ReCell donor sites were healed than Controls (P = .04). Over the first 16 weeks, patients reported significantly less pain at the ReCell donor sites compared with Controls (P ≤ .05 at each time point). Long-term patients reported higher satisfaction with ReCell donor site outcomes compared with the Controls. This study provides evidence that the treatment of deep partial-thickness burns with ASCS results in comparable healing, with significantly reduced donor site size and pain and improved appearance relative to STSG