Can I Tell You the Truth? A Comparative Perspective on Regulating Off-Label Scientific and Medical Information

American pharmaceutical manufacturers are under siege. Even casual observers of this sector recognize the severe challenges to the prevailing business model: declining research productivity; heightened regulatory focus on safety and comparative outcomes with a correspondingly low number of new product approvals; decreasing market capitalization of mature companies; increasing product liability claims; evolving price restraints in the face of increasing managed care market power; and the looming uncertainty of the effects of federal health care reform. But, in fact, the single greatest threat to the pharmaceutical industry may be the policy environment within the United States, which is restricting the ability of companies to speak truthfully with physicians about their products. During the past decade drug companies have endured intrusive government investigations of their business practices, particularly with respect to the marketing and promotion of their products. Firms face extraordinary civil and criminal liability if they discuss or otherwise attempt to influence prescribing other than for the indications approved by the U.S. Food and Drug Administration (FDA). There are now well more than one hundred ongoing civil and criminal investigations involving the U.S. Department of Justice (DOJ) and units of the U.S. Department of Health and Human Services (HHS), as well as associated investigations run by state attorneys general. Billions of dollars in civil and criminal penalties have been paid to date for alleged wrongdoing, and many billions more surely will be paid in the coming years, on top of the costs of the investigations themselves and the potential further liability that may stem from related private class actions brought by plaintiffs\u27 counsel. The concomitant media and political scrutiny has irreparably harmed the reputation of the industry. If the history of Western civilization may be seen as one long battle pitting order against freedom, the government\u27s effort to curtail off-label speech might be dismissed as a minor skirmish on the outskirts of town. However, this issue is anything but minor in policy terms. The eventual outcome will have significant implications for the practice of medicine, the development of new drugs, and the public health

The chiral phase transition in charge ordered 1T-TiSe2

It was recently discovered that the low temperature, charge ordered phase of 1T-TiSe2 has a chiral character. This unexpected chirality in a system described by a scalar order parameter could be explained in a model where the emergence of relative phase shifts between three charge density wave components breaks the inversion symmetry of the lattice. Here, we present experimental evidence for the sequence of phase transitions predicted by that theory, going from disorder to non-chiral and finally to chiral charge order. Employing X-ray diffraction, specific heat, and electrical transport measurements, we find that a novel phase transition occurs ~7 K below the main charge ordering transition in TiSe2, in agreement with the predicted hierarchy of charge ordered phases.Comment: 5 pages, 3 figures; includes additional experimental and theoretical results; fixed typo

True Metabolized Energy of Submersed Aquatic Vegetation in Semi-Permanent Marshes for Dabbling Ducks in the Upper Midwest Annual Performance Report Period: 1 July 2015 – 30 June 2016

Our primary objectives were to 1) estimate true metabolizable energy of common species of submersed aquatic vegetation in semi-permanent marsh habitats of the Upper Midwest for gadwall and mallard during autumns 2015–2017, and 2) use current and historic estimates of semi-permanent marsh vegetation communities during autumn within the IRV to document the net change in energetic carrying capacity for dabbling ducks and compare with habitat use by waterfowl using long-term aerial surveys of the Illinois Natural History Survey. We assayed six species of SAV common in the Midwest and that have been previously documented as waterfowl foods: coontail (Ceratophyllum demersum), wild celery (Vallisneria americana), Canadian waterweed (Elodea canadensis), southern naiad (Najas guadalupensis), Eurasian watermilfoil (Myriophyllum spicatum), and sago pondweed (Stuckenia pectinate; Anderson 1959, Stewart 1962, Bergman 1973, Havera 1999, Benedict and Hepp 2000, Hitchcock 2009, Baldassarre 2014). Understanding the energetic value of SAV for dabbling ducks will allow wetland managers to accurately evaluate wetland management practices and conservation planners to develop more accurate energetic carrying capacity models. We predicted that the energetic carrying capacity of semi-permanent marshes containing SAV will be slightly less than if the same wetlands were managed for moist-soil vegetation (Bowyer et al. 2005). We hypothesized that the TME of SAV per unit biomass will be less than that of moist-soil seeds and agricultural grains. Further, we hypothesized that the TME values derived from male and female mallards and between time periods (week of trial) will be similar.United States Fish and Wildlife Service Contract Number: F15AP00687unpublishednot peer reviewedOpe

Epidemiology of Herpes Simplex Virus Infection in Pregnancy: A Pilot Study:

Herpes simplex virus (HSV) infection is one of the most common sexually transmitted viral diseases worldwide. HSV type 2 causes most genital herpes and HSV type 1 is usually transmitted via non-sexual contacts. We studied 109 pregnant women between January 2007 and December 2008, in relation to their age, condom use, number of sexual partners, age at first intercourse, parity and smoking habits. The aim of this study is to evaluate the prevalence of HSV cervical infection and HSV co-infection with other genital microorganisms associated with poor neonatal outcome. Our results show that of the 109 outpatients enrolled, 30% were HSV1 and/or HSV2 positive, of whom 30% were infected with both HSV1 and HSV2, 18% were infected with HSV1 alone and 52% with HSV2 alone. A significant association between HSV1 and HSV2 infection was found, and the prevalence of HSV2 infection in women infected with HSV1 was 63%. The prevalence of HSV1/2 varied in the presence of other vaginal microorganisms but a statistical significant association was not found. This pilot study is probably too small to obtain statistically significant results. Nevertheless, using these observed results, we calculated that about 530 patients with comparable features should be enrolled to detect an increase of 50% in HSV infection due to the presence of other genital infections and potential risk factors

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Velocity Selection for Propagating Fronts in Superconductors

Using the time-dependent Ginzburg-Landau equations we study the propagation of planar fronts in superconductors, which would appear after a quench to zero applied magnetic field. Our numerical solutions show that the fronts propagate at a unique speed which is controlled by the amount of magnetic flux trapped in the front. For small flux the speed can be determined from the linear marginal stability hypothesis, while for large flux the speed may be calculated using matched asymptotic expansions. At a special point the order parameter and vector potential are dual, leading to an exact solution which is used as the starting point for a perturbative analysis.Comment: 4 pages, 2 figures; submitted to Phys. Rev. Letter

Effects of reduced carbonic anhydrase activity on CO₂ assimilation rates in Setaria viridis: a transgenic analysis

In C₄ species, the major β-carbonic anhydrase (β-CA) localized in the mesophyll cytosol catalyses the hydration of CO₂ to HCO₃-, which phosphoenolpyruvate carboxylase uses in the first step of C₄ photosynthesis. To address the role of CA in C₄ photosynthesis, we generated transgenic Setaria viridis depleted in β-CA. Independent lines were identified with as little as 13% of wild-type CA. No photosynthetic defect was observed in the transformed lines at ambient CO₂ partial pressure (pCO₂). At low pCO₂, a strong correlation between CO₂ assimilation rates and CA hydration rates was observed. C18O16O isotope discrimination was used to estimate the mesophyll conductance to CO₂ diffusion from the intercellular air space to the mesophyll cytosol (gm) in control plants, which allowed us to calculate CA activities in the mesophyll cytosol (Cm). This revealed a strong relationship between the initial slope of the response of the CO₂ assimilation rate to cytosolic pCO₂ (ACm) and cytosolic CA activity. However, the relationship between the initial slope of the response of CO₂ assimilation to intercellular pCO₂ (ACi) and cytosolic CA activity was curvilinear. This indicated that in S. viridis, mesophyll conductance may be a contributing limiting factor alongside CA activity to CO₂ assimilation rates at low pCO₂.This research was supported by the Bill and Melinda Gates Foundation’s funding for the C₄ Rice consortium and by the Australian Research Council Centre of Excellence for Translational Photosynthesis (CE140100015). RES is funded by ARC DECRA (DE130101760)