Do Libraries Still Need Book Vendors and Subscription Agents?

Digital content blurs the lines of traditional library acquisition workflows and organization. For example: link resolvers and the loading of order confirmation record files may be handled by systems staff in one organization and by technical services staff in another. Lines are being crossed between acquisitions and interlibrary loan functions, notably with electronic versions of theses and dissertations. Regardless of this blurring of lines, library staff use vendors still in acquiring content for the library collection. The reasons for using vendors have stood for decades, but are changes in the information industry having an impact? In the current environment, what interactions with vendors are most useful to a library

Innovative regenerative medicines in the EU : a better future in evidence?

Background Despite a steady stream of headlines suggesting they will transform the future of healthcare, high-tech regenerative medicines have, to date, been quite inaccessible to patients; only eight have been granted an EU marketing licence in the last seven years. Here, we outline some of the historical reasons for this paucity of licensed innovative regenerative medicines. We discuss the challenges to be overcome to expedite the development of this complex and rapidly changing area of medicine, together with possible reasons to be more optimistic for the future. Discussion Several factors have contributed to the scarcity of cutting-edge regenerative medicines in clinical practice. These include the great expense and difficulties involved in planning how individual therapies will be developed, manufactured to commercial levels, and ultimately successfully delivered to patients. Specific challenges also exist when evaluating the safety, efficacy and cost-effectiveness of these therapies. Furthermore, many treatments are used without a licence from the EMA - under “Hospital Exemption” from the EC legislation. For products which are licensed, alternative financing approaches by healthcare providers may be needed, since many therapies will have significant up-front costs but uncertain benefits and harms in the long-term. However, increasing political interest and more flexible mechanisms for licensing and paying for therapies are now evident. These could be key to the future growth and development of regenerative medicine in clinical practice. Conclusions Recent developments in regulatory processes, coupled with increasing political interest may offer some hope for improvements to the long and often difficult routes from laboratory to marketplace for leading-edge cell or tissue therapies. Collaboration between publicly-funded researchers and the pharmaceutical industry could be key to the future development of regenerative medicine in clinical practice; such collaborations might also offer a possible antidote to the innovation crisis in the pharmaceutical industry

Propagule Pressure and Stream Characteristics Influence Introgression: Cutthroat and Rainbow Trout in British Columbia

Hybridization and introgression between introduced and native salmonids threaten the continued persistence of many inland cutthroat trout species. Environmental models have been developed to predict the spread of introgression, but few studies have assessed the role of propagule pressure. We used an extensive set of fish stocking records and geographic information system (GIS) data to produce a spatially explicit index of potential propagule pressure exerted by introduced rainbow trout in the Upper Kootenay River, British Columbia, Canada. We then used logistic regression and the information-theoretic approach to test the ability of a set of environmental and spatial variables to predict the level of introgression between native westslope cutthroat trout and introduced rainbow trout. Introgression was assessed using between four and seven co-dominant, diagnostic nuclear markers at 45 sites in 31 different streams. The best model for predicting introgression included our GIS propagule pressure index and an environmental variable that accounted for the biogeoclimatic zone of the site (r2¼0.62). This model was 1.4 times more likely to explain introgression than the next-best model, which consisted of only the propagule pressure index variable. We created a composite model based on the model-averaged results of the seven top models that included environmental, spatial, and propagule pressure variables. The propagule pressure index had the highest importance weight (0.995) of all variables tested and was negatively related to sites with no introgression. This study used an index of propagule pressure and demonstrated that propagule pressure had the greatest influence on the level of introgression between a native and introduced trout in a human-induced hybrid zone

Modern saltmarsh diatom distributions of the Outer Banks, North Carolina, and the development of a transfer function for high resolution reconstructions of sea level

We collected modern diatom samples from Currituck Barrier Island, Oregon Inlet and Pea Island marshes, Outer Banks, North Carolina, USA, which have different salinity regimes due to their varying distances from a major barrier island inlet. Multivariate analyses separate the saltmarsh diatom assemblages into distinct elevational zones, dominated by differing abundances of polyhalobous, mesohalobous and oligohalobous taxa, suggesting that the distribution of saltmarsh diatoms is a direct function of elevation, with the most important controlling factors being the duration and frequency of subaerial exposure. We developed the first diatom-based transfer function for the east coast of North America to reconstruct former sea levels based upon the relationship between diatom assemblage and elevation. Results imply that this is possible to a precision of ±0.08 m, superior to most similar studies from temperate, mid-latitude environments. The transfer function is used to construct a relative sea-level curve from fossil assemblages from Salvo, North Carolina. These results suggest a sea-level rise of 0.7 m over the last c. 150 years, at an average of c. 3.7 mm year−1. This is consistent with existing sea-level data, and illustrates the utility of the transfer function approach

The HIV-associated tuberculosis epidemic--when will we act?

Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART). This approach should result in short-term and long-term declines in tuberculosis incidence through individual immune reconstitution and reduced HIV transmission. Implementation of the 3Is policy (intensified tuberculosis case finding, infection control, and isoniazid preventive therapy) for prevention of HIV-associated tuberculosis, combined with earlier start of ART, will reduce the burden of tuberculosis in people with HIV infection and provide a safe clinical environment for delivery of ART. Some progress is being made in provision of HIV care to HIV-infected patients with tuberculosis, but too few receive co-trimoxazole prophylaxis and ART. We make practical recommendations about how to improve this situation. Early HIV diagnosis and treatment, the 3Is, and a comprehensive package of HIV care, in association with directly observed therapy, short-course (DOTS) for tuberculosis, form the basis of prevention and control of HIV-associated tuberculosis. This call to action recommends that both HIV and tuberculosis programmes exhort implementation of strategies that are known to be effective, and test innovative strategies that could work. The continuing HIV-associated tuberculosis epidemic needs bold but responsible action, without which the future will simply mirror the past

The assessment and appraisal of regenerative medicines and cell therapy products : an exploration of methods for review, economic evaluation and appraisal

BACKGROUND: The National Institute for Health and Care Excellence (NICE) commissioned a 'mock technology appraisal' to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal. METHODS: Our research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia. RESULTS: An assessment of previous evaluations of regenerative medicines found that, although there were a number of evidential challenges, none was unique to regenerative medicines or was beyond the scope of existing methods used to conceptualise decision uncertainty. Regarding the clinical evidence for regenerative medicines, the issues were those associated with a limited evidence base but were not unique to regenerative medicines: small non-randomised studies, high variation in response and the intervention subject to continuing development. The relative treatment effects generated from single-arm trials are likely to be optimistic unless it is certain that the historical data have accurately estimated the efficacy of the control agent. Pivotal trials may use surrogate end points, which, on average, overestimate treatment effects. To reduce overall uncertainty, multivariate meta-analysis of all available data should be considered. Incorporating indirectly relevant but more reliable (more mature) data into the analysis can also be considered; such data may become available as a result of the evolving regulatory pathways being developed by the European Medicines Agency. For the exemplar case of CAR T-cell therapy, target product profiles (TPPs) were developed, which considered the 'curative' and 'bridging to stem-cell transplantation' treatment approaches separately. Within each TPP, three 'hypothetical' evidence sets (minimum, intermediate and mature) were generated to simulate the impact of alternative levels of precision and maturity in the clinical evidence. Subsequent assessments of cost-effectiveness were undertaken, employing the existing NICE reference case alongside additional analyses suggested within alternative frameworks. The additional exploratory analyses were undertaken to demonstrate how assessments of cost-effectiveness and uncertainty could be impacted by alternative managed entry agreements (MEAs), including price discounts, performance-related schemes and technology leasing. The panel deliberated on the range of TPPs, evidence sets and MEAs, commenting on the likely recommendations for each scenario. The panel discussed the challenges associated with the exemplar and regenerative medicines more broadly, focusing on the need for a robust quantification of the level of uncertainty in the cost-effective estimates and the potential value of MEAs in limiting the exposure of the NHS to high upfront costs and loss associated with a wrong decision. CONCLUSIONS: It is to be expected that there will be a significant level of uncertainty in determining the clinical effectiveness of regenerative medicines and their long-term costs and benefits, but the existing methods available to estimate the implications of this uncertainty are sufficient. The use of risk sharing and MEAs between the NHS and manufacturers of regenerative medicines should be investigated further. FUNDING: The National Institute for Health Research Health Technology Assessment programme