Making memories last: the synaptic tagging and capture hypothesis

The synaptic tagging and capture hypothesis of protein synthesis-dependent long-term potentiation asserts that the induction of synaptic potentiation creates only the potential for a lasting change in synaptic efficacy, but not the commitment to such a change. Other neural activity, before or after induction, can also determine whether persistent change occurs. Recent findings, leading us to revise the original hypothesis, indicate that the induction of a local, synapse-specific 'tagged' state and the expression of long-term potentiation are dissociable. Additional observations suggest that there are major differences in the mechanisms of functional and structural plasticity. These advances call for a revised theory that incorporates the specific molecular and structural processes involved. Addressing the physiological relevance of previous in vitro findings, new behavioural studies have experimentally translated the hypothesis to learning and the consolidation of newly formed memories.     

Options for change in the NHS consultant contract.

The lead negotiators for the management and consultant sides in an NHS trust in northern England responded to debate in their trust about consultant contracts by offering to research the attitudes of their peers towards a variety of contract options. The options tested included the current contract; models already examined in the trust and elsewhere, such as time sensitive and mild performance related contracts; and some more radical and speculative possibilities, including consultants franchising their services to the trust. Beyond the predictable conclusion that consultants would prefer no change while managers desired it, a time sensitive contract emerged as having potential for successful negotiation. On the other hand, neither consultants nor managers favoured a strict performance related contract or a fee for service contract. There was a strong similarity of opinion between the two groups on the relative salary values of the options, though the consultants consistently priced these higher than the managers.     

Biotechnology and sustainability: the role of transatlantic cooperation in research and innovation

Life sciences and biotechnology are increasingly providing sustainable solutions in a wide range of areas from medicine to industry, agriculture and the environment. The United States and Europe are the two largest regions in which the revolution in life sciences and biotechnology has been taking place. Established in 1990, the EC-US Task Force on Biotechnology Research has provided a fruitful forum for the exchange of information, for the discussion of ideas and for the joint sponsoring of research activities between the US and the European Union.     

Managing change: the human aspects of the NHS.

Whatever ministers actually decide about London following the Tomlinson report, the changes are likely to be large-scale and affect many staff and patients. Therefore how well those changes are handled becomes crucial to their success. The NHS has much to learn from other industries and organisations that have been through similar changes. Firstly, there needs to be an overall strategy for the change, rather than individual units trying to manage their own parts of it in an ad hoc way. Secondly, how well those made redundant are treated is an important factor in maintaining the morale of those who stay behind. For those affected by changes the NHS needs to provide full information, imagination, time, emotional and practical support, and money. Though decisions need to be made quickly, their implementation should take as much time as is necessary.     

Developing biodiversity indicators for cities: applying the DPSIR model to Nagoya and integrating social and ecological aspects

Capturing the trends and status of urban biodiversity is challenged by current rapid changes, including increasing population flow into urban areas and multiple pressures on neighboring ecosystems. For this reason, this article aims to highlight relevant findings from both ecological and social sciences in the development of urban and biodiversity indicators. It examines the applicability of a model to an urban city in Japan. The objectives of this study are threefold. First, it reviews and summarizes the historical development and relevant existing studies of urban and biodiversity indicators, the “Drivers-Pressure-State-Impact-Response” (DPSIR) model is presented, and its main critiques are summarized. Second, trends in scientific studies in specific journals are identified. Third, practical lessons for a Japanese local municipality, the city of Nagoya, are derived from two previous sets of reviews. The applicability of the “DPSIR” to current practices in the city of Nagoya is examined to assess the relevance of the model to real situations.     

Making the internal market work: a case for managed change.

The internal market in the NHS is meant to ensure that provider units compete on the basis of price and quality and that money follows patients into efficient units. But the example of what happened to one local ophthalmology unit suggests what may go wrong when entrepreneurial activity is applied in a market that does not work perfectly. In 1991-2 the unit had a high workload but also comparatively high prices (because of crude pricing in the local hospital); because of pressure of work the waiting times lengthened and general practitioners increasingly complained about the service. The staff in the unit reopened a longstanding debate about the need for a third consultant ophthalmologist, but neither the purchasers (including fundholders) nor the provider unit were able to fund the post. Fundholders in a neighbouring district, however, together with that district health authority, decided to place their contracts elsewhere for the following year. Although the withdrawal of contracts jeopardised the clinical and financial viability of the ophthalmic unit, patients continued to use the service. When general practitioners in the district realised that their local service might collapse they pressed to keep the service open. The fundholders and the host purchaser finally agreed to fund a third consultant and drew up standards for the service. As a result the waiting times fell and the service is now described as "excellent." Short term market decisions may have unforseen long term implications for services to patients. This needs to be addressed as part of the evolution of the reformed NHS.     

Individual-based modeling of phytoplankton: evaluating approaches for applying the cell quota model

Present phytoplankton models typically use a population-level (lumped) modeling (PLM) approach that assumes average properties of a population within a control volume. For modern biogeochemical models that formulate growth as a nonlinear function of the internal nutrient (e.g. Droop kinetics), this averaging assumption can introduce a significant error. Individual-based (agent-based) modeling (IBM) does not make the assumption of average properties and therefore constitutes a promising alternative for biogeochemical modeling. This paper explores the hypothesis that the cell quota (Droop) model, which predicts the population-average specific growth or cell division rate, based on the population-average nutrient cell quota, can be applied to individual algal cells and produce the same population-level results. Three models that translate the growth rate calculated using the cell quota model into discrete cell division events are evaluated, including a stochastic model based on the probability of cell division, a deterministic model based on the maturation velocity and fraction of the cell cycle completed (maturity fraction), and a deterministic model based on biomass (carbon) growth and cell size. The division models are integrated into an IBM framework (iAlgae), which combines a lumped system representation of a nutrient with an individual representation of algae. The IBM models are evaluated against a conventional PLM (because that is the traditional approach) and data from a number of steady and unsteady continuous (chemostat) and batch culture laboratory experiments. The stochastic IBM model fails the steady chemostat culture test, because it produces excessive numerical randomness. The deterministic cell cycle IBM model fails the batch culture test, because it has an abrupt drop in cell quota at division, which allows the cell quota to fall below the subsistence quota. The deterministic cell size IBM model reproduces the data and PLM results for all experiments and the model parameters (e.g. maximum specific growth rate, subsistence quota) are the same as those for the PLM. In addition, the model-predicted cell age, size (carbon) and volume distributions are consistent with those derived analytically and compare well to observations. The paper discusses and illustrates scenarios where intra-population variability in natural systems leads to differences between the IBM and PLM models.     

Making evolution stick: using sticky notes to teach the mechanisms of evolutionary change

Evolution and its mechanisms of action are concepts that unite all aspects of biology, but remain some of the most difficult for students to understand. To address this challenge, we designed a hands-on activity that introduces fundamental mechanisms of evolutionary change: natural selection, genetic drift, and gene flow. In small groups, students use a population of sticky notes to reveal the consequences of each mechanism on phenotype frequency. In a follow-up homework assignment, students then explore how changes in phenotype frequency reflect changes in allele frequency in the population. This activity is suitable for anyone learning the basics of evolution, from high-school through the undergraduate level. We have provided detailed instructions, in-class worksheets, follow-up homework, and extensions that allow the activity to be simplified or made more complex as needed. In our own classrooms, we have observed that the concrete and collaborative nature of this activity enables students to deepen their understanding of the mechanisms through which evolution occurs. We have designed this study such that, in completing this activity, we hope to offer students the opportunity to confront potential misconceptions about evolution and gain a solid foundation for future explorations in the discipline.     

Exploring scale-up,spread, and sustainability: an instrumental case study tracing an innovation to enhance dysphagia care

Background

Adoption, adaptation, scale-up, spread, and sustainability are ill-defined, undertheorised, and little-researched implementation science concepts. An instrumental case study will track the adoption and adaptation, or not, of a locally developed innovation about dysphagia as a patient safety issue. The case study will examine a conceptual framework with a continuum of spread comprising hierarchical control or ‘making it happen’, participatory adaptation or ‘help it happen’, and facilitated evolution or ‘let it happen’.

Methods

This case study is a prospective, longitudinal design using mixed methods. The fifteen-month (October 2012 to December 2013) instrumental case study is set in large, healthcare organisation in England. The innovation refers to introducing a nationally recognised, inter-disciplinary dysphagia competency framework to guide workforce development about fundamental aspects of care. Adoption and adaptation will be examined at an organisational level and along two, contrasting care pathways: stroke and fractured neck of femur. A number of educational interventions will be deployed, including training a cadre of trainers to cascade the essentials of dysphagia management and developing a Dysphagia Toolkit as a learning resource. Mixed methods will be used to investigate scale-up, spread, and sustainability in acute and community settings. A purposive sample of senior managers and clinical leaders will be interviewed to identify path dependency or the context specific particularities of implementation. A pre- and post-evaluation, using mealtime observations and a survey, will investigate the learning effect on staff adherence to patient specific dysphagia recommendations and attitudes towards dysphagia, respectively. Official documents and an ethnographic field journal allow critical junctures, temporal aspects and confounding factors to be explored.

Discussion

Researching spread and sustainability presents methodological and practical challenges. These include fidelity, adaptation latitude, time, and organisational changes. An instrumental case study will allow these confounding factors to be tracked over time and in place. The case study is underpinned by, and will test a conceptual framework about spread, to explore theoretical generalizability.

     

Impact of NHS walk-in centres on the workload of other local healthcare providers: time series analysis

ObjectivesTo assess the impact of NHS walk-in centres on the workload of local accident and emergency departments, general practices, and out of hours services.DesignTime series analysis in walk-in centre sites with no-treatment control series in matched sites.SettingWalk-in centres and matched control towns without walk-in centres in England.Participants20 accident and emergency departments, 40 general practices, and 14 out of hours services within 3 km of a walk-in centre or the centre of a control town.ResultsA reduction in consultations at emergency departments (–175 (95% confidence interval –387 to 36) consultations per department per month) and general practices (–19.8 (−53.3 to 13.8) consultations per 1000 patients per month) close to walk-in centres became apparent, although these reductions were not statistically significant. Walk-in centres did not have any impact on consultations on out of hours services.ConclusionIt will be necessary to assess the impact of walk-in centres in a larger number of sites and over a prolonged period, to determine whether they reduce the demand on other local NHS providers.

What is already known on this topic

One of the objectives for NHS walk-in centres was to reduce demand on other NHS services, particularly general practitioners'' services and accident and emergency departmentsStudies of walk-in centres in North America have indicated that such centres do not reduce demand on other healthcare servicesStudies of minor injuries units in the United Kingdom (which have some similarities with walk-in centres) indicate that these units substitute mainly for consultations in accident and emergency departments

What this study adds

The data imply that walk-in centres may moderate the increasing demand on general practice and reduce the number of consultations in accident and emergency departmentsThe high level of background variability in consultation rates means that any impact of a walk-in centre is not statistically significantTo draw robust conclusions about the impact of walk-in centres on other health providers will require study of a large number of sites over an extended period of time     

Trans-Atlantic collaboration: applying lessons learned from the US CF Foundation quality improvement initiative

Background

Between 2002 and 2006 France launched a national cystic fibrois (CF) newborn screening program; organized a network of specialized CF care centers; and issued CF diagnostic and treatment standards. To continue to build on this success in 2007 the Cystic Fibrosis Center of Expertise for Rare Diseases (CF CERD) of Nantes-Roscoff in partnership with the French CF Society, the French CF Association (Vaincre la Mucoviscidose), and all CF center leaders from across the country agreed to pursue center-level improvement in medical outcomes for people with CF by adapting the U.S. Cystic Fibrosis Foundation’s (US CFF) national initiative, Accelerating the Rate of Improvement in CF Care. To launch the Program to Improve Results and Expertise in CF (le Programme d’Amélioration des Résultats et de l’Expertise en Mucoviscidose - PHARE-M), French leaders pursued mentorship and guidance from leaders at the US CFF, the Dartmouth Institute (TDI), and clinical care teams at CF centers across the U.S.

Methods

The following activities enabled the Nantes-Roscoff CF CERD team members and a parent, involved with the French CF Association board and a quality engineer by training, to gain the leadership and quality improvement knowledge and skills necessary to implement the PHARE-M program: 1) regularly attending national meetings, tracking publications, and leveraging existing partnerships; 2) completing two sabbaticals to visit U.S. CF centers and enrolling in academic and professional training courses; and, 3) inviting US CFF and TDI leaders to France to meet key opinion leaders and frontline teams.

Conclusions

The Nantes-Roscoff CF CERD team successfully adapted the US CFF’s initiative to accelerate improvement in CF care by establishing a partnership with U.S. leaders to communicate and exchange strategies and lessons learned; intentionally studying and adapting the Clinical Microsystems approach to quality improvement; and learning directly from the experience of frontline teams in the U.S. They continue to partner with U.S. leaders and are seeking to collaborate with European colleagues to continue to improve care for individuals with CF and their families across Europe.

     

A pulse fishery model with closures as function of the catch: conditions for sustainability

We present a model of single species fishery which alternates closed seasons with pulse captures. The novelty is that the length of a closed season is determined by the remaining stock size after the last capture. The process is described by a new type of impulsive differential equations recently introduced. The main result is a fishing effort threshold which determines either the sustainability of the fishery or the extinction of the resource.