Reformulation Strategy Research Articles

Chimeric GII.4 norovirus virus-like-particle-based vaccines induce broadly blocking immune responses.

There is currently no licensed vaccine for noroviruses, and development is hindered, in part, by an incomplete understanding of the host adaptive immune response to these highly heterogeneous viruses and rapid GII.4 norovirus molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs every 2 to 4 years. To address the problem of GII.4 antigenic variation, we tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine platforms, which incorporate antigenic determinants from multiple strains into a single genetic background, will elicit a broader immune response against contemporary and emergent strains. Here, we compare the immune response generated by chimeric VLPs to that of parental strains and a multivalent VLP cocktail. Results demonstrate that chimeric VLPs induce a more broadly cross-blocking immune response than single parental VLPs and a similar response to a multivalent GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone from one strain into the background of another is sufficient to induce a blockade response against the strain donating epitope site A. This suggests a mechanism by which population-wide surveillance of mutations in a single epitope could be used to evaluate antigenic changes in order to identify potential emergent strains and quickly reformulate vaccines against future epidemic strains as they emerge in human populations. Noroviruses are gastrointestinal pathogens that infect an estimated 21 million people per year in the United States alone. GII.4 noroviruses account for >70% of all outbreaks, making them the most clinically important genotype. GII.4 noroviruses undergo a pattern of epochal evolution, resulting in the emergence of new strains with altered antigenicity over time, complicating vaccine design. This work is relevant to norovirus vaccine design as it demonstrates the potential for development of a chimeric VLP-based vaccine platform that may broaden the protective response against multiple GII.4 strains and proposes a potential reformulation strategy to control newly emergent strains in the human population.

The Effect of Six Different Corrective Feedback Strategies on Iranian English Language Learners’ IELTS Writing Task 2

Scholars have long studied the effect of corrective feedback strategies on the writing ability of language learners, but few have formed designs in which more than three feedback strategies have been used. In this research, the ultimate goal was to discover how International English Language Testing System (IELTS-) candidates could be helped to perform better in the writing component of the test with the feedback they get. To this end, 186 learners attending IELTS preparation classes in three different English language institutes participated in this quasi-experimental study. A one-way ANOVA was run to discover the significant difference among the six groups. The findings proposed that Iranian English as a Foreign Language (EFL) students’ writing ability improved as a result of the employment of writing feedback strategies but that reformulation strategy was the most effective one. Teachers can, thus, benefit from the finding of this research by studying the way they should tackle the learners’ inaccurate productions as far as different writing score band descriptors are concerned.

Product reformulation in the food system to improve food safety. Evaluation of policy interventions

The objective of this study is to understand the level of attention that the consumer awards to a balanced diet and to product ingredients, with a twofold purpose: to understand whether food product reformulation can generate a competitive advantage for companies that practice it and to evaluate the most appropriate policy interventions to promote a healthy diet. Reformulation strategy, in the absence of binding rules, could be generated by consumers. Results from qualitative research and from empirical analysis have shown that the question of health is a latent demand influenced by two main factors: a general lack of information, and the marketing strategies adopted by companies which bring about an increase in the information asymmetry between producers and consumers. In the absence of binding rules, it is therefore necessary that the government implement information campaigns (food education) aimed at increasing knowledge regarding the effects of unhealthy ingredients, in order to inform and improve consumer choice. It is only by means of widespread information campaigns that food product reformulation can become a strategic variable and allow companies to gain a competitive advantage. This may lead to virtuous results in terms of reducing the social costs related to an unhealthy diet.

Pharmacokinetics of Non-Intravenous Formulations of Fentanyl

Fentanyl was structurally designed by Paul Janssen in the early 1960s as a potent opioid analgesic (100-fold more potent than morphine). It is a full agonist at μ-opioid receptors and possesses physicochemical properties, in particular a high lipophilicity (octanol:water partition coefficient >700), which allow it to cross quickly between plasma and central nervous target sites (transfer half-life of 4.7-6.6 min). It undergoes first-pass metabolism via cytochrome P450 3A (bioavailability ~30 % after rapid swallowing), which can be circumvented by non-intravenous formulations (bioavailability 50-90 % for oral transmucosal or intranasal formulations). Non-intravenous preparations deliver fentanyl orally-transmucosally, intranasally or transdermally. Passive transdermal patches release fentanyl at a constant zero-order rate for 2-3 days, making them suitable for chronic pain management, as are iontophoretic transdermal systems. Oral transmucosal and intranasal routes provide fast delivery (time to reach maximum fentanyl plasma concentrations 20 min [range 20-180 min] and 12 min [range 12-21 min], respectively) suitable for rapid onset of analgesia in acute pain conditions with time to onset of analgesia of 5 or 2 min, respectively. Intranasal formulations partly bypass the blood-brain barrier and deliver a fraction of the dose directly to relevant brain target sites, providing ultra-fast analgesia for breakthrough pain. Thanks to the development of non-intravenous pharmaceutical formulations, fentanyl has become one of the most successful opioid analgesics, and can be regarded as an example of a successful reformulation strategy of an existing drug based on pharmacokinetic research and pharmaceutical technology. This development broadened the indications for fentanyl beyond the initial restriction to intra- or perioperative clinical uses. The clinical utility of fentanyl could be expanded further by more comprehensive mathematical characterizations of its parametric pharmacokinetic input functions as a basis for the rational selection of fentanyl formulations for individualized pain therapy.

Impact of foods with health logo on saturated fat, sodium and sugar intake of young Dutch adults

Health logos are introduced to distinguish foods with 'healthier' nutrient composition from regular foods. In the present study, we evaluated the effects of changed food compositions according to health logo criteria on the intake of saturated fat, sugar and sodium in a Dutch population of young adults. Foods in the Dutch food composition table were evaluated against nutrient criteria for logo eligibility. Three replacement scenarios were compared with the nutrient intake 'as measured' in the Dutch consumption survey. The foods not complying with health logo criteria were replaced either by 'virtual' foods exactly complying with the health logo criteria, with real 2007 market shares (scenario I) and 100% market shares (scenario II), or by existing similar foods with a composition that already complied with the health logo criteria (scenario III). The percentage reduction in nutrient intake with the current 2007 market shares of 'health logo foods' was -2.5% for SFA, 0% for sodium and -1% for sugar. With a 100% market share these reductions would be -10% for SFA, -4% for sodium and -6% for sugar. This may lead to a reduction of -40% for SFA, -23% for sodium and -36% for sugar in the most optimal replacement scenario. With 'health logo foods', available in 2007 and current consumption patterns, small reductions can be achieved for SFA and sugar. For additional reductions, lowering the fat/sodium content of meat (products) towards health logo criteria and drinks without sugar towards limits far below health logo criteria would be the most effective reformulation strategy.

Generic Entry, Reformulations and Promotion of SSRIs in the US

Previous research has shown that a manufacturer's promotional strategy for a brand name drug is typically affected by generic entry. However, little is known about how newer strategies to extend patent life, including product reformulation introduction or obtaining approval to market for additional clinical indications, influence promotion. To examine the relationships among promotional expenditures, generic entry, reformulation entry and new indication approval. We used quarterly data on national product-level promotional spending (including expenditures for physician detailing and direct-to-consumer advertising [DTCA], and the retail value of free samples distributed in physician offices) for selective serotonin reuptake inhibitors (SSRIs) over the period 1997-2004. We estimated econometric models of detailing, DTCA and total quarterly promotional expenditures as a function of the timing of generic entry, entry of new product formulations and US FDA approval for new clinical indications for existing medications in the SSRI class. Expenditures by pharmaceutical manufacturers for promotion of antidepressant medications was the main outcome measure. Over the period 1997-2004, there was considerable variation in the composition of promotional expenditures across the SSRIs. Promotional expenditures for the original brand molecule decreased dramatically when a reformulation of the molecule was introduced. Promotional spending (both total and detailing alone) for a specific molecule was generally lower after generic entry than before, although the effect of generic entry on promotional spending appears to be closely linked with the choice of product reformulation strategy pursued by the manufacturer. Detailing expenditures for Paxil were increased after the manufacturer received FDA approval to market the drug for generalized anxiety disorder (GAD), while the likelihood of DTCA outlays for the drug was not changed. In contrast, FDA approval to market Paxil and Zoloft for social anxiety disorder (SAD) did not affect the manufacturers' detailing expenditures but did result in a greater likelihood of DTCA outlays. The introduction of new product formulations appears to be a common strategy for attempting to extend market exclusivity for medications facing impending generic entry. Manufacturers who introduced a reformulation before generic entry shifted most promotion dollars from the original brand to the reformulation long before generic entry, and in some cases manufacturers appeared to target a particular promotion type for a given indication. Given the significant impact that pharmaceutical promotion has on demand for prescription drugs in the US, these findings have important implications for prescription drug spending and public health.

Improved lumped-differential formulations and hybrid solution methods for drying in porous media

The present paper illustrates the construction of hybrid tools for the problem formulation and solution methodology towards the simulation of heat and mass transfer during drying in capillary porous media. First, a problem reformulation strategy is discussed, known as the coupled integral equations approach (CIEA), which offers improved lumped-differential formulations in different classes of problems, in comparison against classical lumping schemes, allowing for a reduction on the number of independent variables to be considered in specific formulations. Second, the generalized integral transform technique (GITT) is employed, as a hybrid numerical–analytical solution methodology for convection–diffusion problems. An example is provided related to drying in capillary porous cylindrical media as formulated by the two-dimensional Luikov's system of equations.

A Multi-Stage Stochastic Integer Programming Approach for Capacity Expansion under Uncertainty

This paper addresses a multi-period investment model for capacity expansion in an uncertain environment. Using a scenario tree approach to model the evolution of uncertain demand and cost parameters, and fixed-charge cost functions to model the economies of scale in expansion costs, we develop a multi-stage stochastic integer programming formulation for the problem. A reformulation of the problem is proposed using variable disaggregation to exploit the lot-sizing substructure of the problem. The reformulation significantly reduces the LP relaxation gap of this large scale integer program. A heuristic scheme is presented to perturb the LP relaxation solutions to produce good quality integer solutions. Finally, we outline a branch and bound algorithm that makes use of the reformulation strategy as a lower bounding scheme, and the heuristic as an upper bounding scheme, to solve the problem to global optimality. Our preliminary computational results indicate that the proposed strategy has significant advantages over straightforward use of commercial solvers.

A Case Study in Striation Prevention by Targeted Formulation Adjustment: Aluminum Titanate Sol−Gel Coatings

By careful consideration of the physical and chemical effects responsible for striation defect formation during spin coating, it is possible to adjust a coating solution's recipe to prevent these coating defects from forming. In this paper we present a specific “case study” to illustrate a useful reformulation strategy. Aluminum titanate (Al2TiO5) coatings were made via sol−gel chemical processing. An early version of our sol−gel recipe resulted in coatings that were severely striated and therefore unacceptable for their desired application, even though they had formed the correct crystalline phase during subsequent firing. The present paper examines that specific sol−gel recipe and illustrates a protocol for improving the final coating flatness by selecting a solvent additive that can influence the surface forces during drying. Coatings deposited with the modified solution were smooth and free from striations. The coating morphology was characterized by optical surface profilometry and crystallinity by X...

A Study on Improving the Effectiveness of Information Retrieval Through P-norm, RF, LCAF

Boolean retrieval is simple and elegant. However, since there is no provision for term weighting, no ranking of the answer set is generated. As a result, the size of the output might be too large or too small. Relevance feedback is the most popular query reformulation strategy. in a relevance feedback cycle, the user is presented with a list of the retrieved documents and, after examining them, marks those which are relevant. In practice, only the top 10(or 20) ranked documents need to be examined. The main idea consists of selecting important terms, or expressions, attached to the documents that have been identified as relevant by the user, and of enhancing the importance of these terms in a new query formulation. The expected effect is that the new query will be moved towards the relevant documents and away from the non-relevant ones. Local analysis techniques are interesting because they take advantage of the local context provided with the query. In this regard, they seem more appropriate than global analysis techniques. In a local strategy, the documents retrieved for a given query q are examined at query time to determine terms for query expansion. This is similar to a relevance feedback cycle but might be done without assistance from the user.

Reliability, covering and balanced matrices

This paper addresses a certain generalized covering integer program. The original application that motivated the study of this problem was an emergency services vehicle location problem. The underlying model can also be applied to certain reliability optimization problems. The main contribution of this paper is the definition and analysis of a reformulation strategy. Specifically, we show how the original generalized covering problem can be reformulated as a set covering problem. We then show that for a particular special case the associated constraint matrix is balanced. This in turn implies that the integer program can be efficiently solved using linear programming techniques. This result together with the good computational results reported in a previous paper constitute substantial evidence as to the overall effectiveness of the reformulation strategy. Furthermore, they indicate that the generalized covering model addressed can be effectively solved in a fairly wide range of cases.

Speech monitoring skills in Alzheimer's disease, Parkinson's disease, and normal aging

We examined the abilities of 15 patients with dementia of the Alzheimer type (DAT), 22 patients with Parkinson's Disease (PD), and 141 healthy subjects (ranging in age from 30 to 79 years) to detect and correct their own speech errors. Each subject was shown the Cookie Theft picture of the BDAE (Goodglass & Kaplan, 1972., The assessment of aphasia and related disorders. Philadelphia: Lea & Febiger.) and instructed to tell the examiner the “ … story of what's happening in the picture.” Self-monitoring performance was assessed by tabulating the number of uncorrected errors as well as repaired errors. We divided repairs into two types based on the psycholinguistics literature ( van Wijk & Kempen, 1987. Cognitive Psychology, 19, 403–440). Speech corrections were judged to be lemma repairs when the reparandum was a single word, and reformulation repairs when a new syntactic constituent was added to the reparandum. Patients with DAT corrected only 24% of their total errors and patients with PD only 25%. Healthy subjects, by contrast, corrected from 72 to 92% of their total errors. Patients with DAT tended to rely on reformulation repairs while patients with PD used both repair types about equally often. While healthy elderly Ss (in the 70s group) utilized lemma repairs more often than the reformulation strategy, all other healthy Ss used both strategies about equally often. Across all groups naming performance correlated negatively with numbers of undetected errors. Results point to a previously unrecognized communication disorder associated with PD and DAT and manifested by an impairment in the ability to correct output errors. This impairment may be related to attentional and frontal dysfunction in the two patient groups.

About reformulation in full-text IRS

In this paper, we analyze different kinds of reformulation used in Information Retrieval systems where full-text databases are accessed through natural language queries. These reformulations are tested separately on large actual full-text databases managed by the SPIRIT system (Syntactic and Probabilistic Indexing and Retrieval of Information in Texts). Some modifications on the weighted comparison are being tested for taking reformulation into account. At the end, an expert system solution is proposed as a reformulation strategy manager.