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Hill, MW, Roberts, M, Price, MJ, and Kay, AD. Effects of flywheel training with eccentric overload on standing balance, mobility, physical function, muscle thickness, and muscle quality in older adults. J Strength Cond Res 36(11): 3190-3199, 2022-This study investigated the effects of a 6-week eccentric overload flywheel training program on vastus lateralis (VL) and gastrocnemius medialis (GM) muscle thickness and muscle quality (echo intensity), mobility (Timed Up and Go [TUG]), physical function (sit-to-stand), and balance (postural sway) performance. Nineteen subjects were assigned to either a flywheel training group ( n = 11, age = 66.4 ± 5.2 years) or a control group ( n = 8, age = 65.9 ± 3.8 years). The flywheel group underwent twice weekly squat and calf raise exercises for 6 weeks with outcome measures assessed before and after training or a time-matched control period. Throughout the training, subjects were instructed to contract as fast as possible with maximal effort during the concentric phase and to maximally resist the pull during the eccentric phase. The alpha value was a priori set at p0.05. Statistically significant ( p0.05) mean ( SD ) increases in right and left VL (7.6-9.6 ± 7.7-9.8%) and GM (8.6-8.7 ± 6.4-11.5%) muscle thickness and a reduction in VL (10.2-11.3 ± 5.9-7.9%) and GM (11.7-11.9 ± 5.6-9.6%) echo intensity were accompanied by faster TUG time (13.7 ± 7.0%) improved sit-to-stand performance (17.8-23.5 ± 7.6 - 13.4%) and reduced postural sway (29.7-42.3 ± 13.2-24.2%) after 6 weeks of flywheel training. There were no differences in any outcome measures between the treatment and control group at baseline ( p0.05). Overall, we observed substantial gains in muscle thickness and muscle quality, in addition to enhanced physical function, balance, and mobility performance among older adults after flywheel training, which may have important implications for preserving the functional capacity of older adults.

Objective To investigate the effect of formulation parameters on the preparation of transfersomes as sustained-release delivery systems for lidocaine and to develop and validate a new high-performance liquid chromatography (HPLC) method for analysis. Method Taguchi design of experiment (DOE) was used to optimise lidocaine-loaded transfersomes in terms of phospholipid, edge activator (EA) and phospholipid : EA ratio. Transfersomes were characterised for size, polydispersity index (PDI), charge and entrapment efficiency (%EE). A HPLC method for lidocaine quantification was optimised and validated using a mobile phase of 30%v/v PBS (0.01 m) : 70%v/v Acetonitrile at a flow rate of 1 ml/min, detected at 255 nm with retention time of 2.84 min. The release of lidocaine from selected samples was assessed in vitro. Key findings Transfersomes were 200 nm in size, with PDI ~ 0.3. HPLC method was valid for linearity (0.1–2 mg/ml, R2 0.9999), accuracy, intermediate precision and repeatability according to ICH guidelines. The %EE was between 44% and 56% and dependent on the formulation parameters. Taguchi DOE showed the effect of factors was in the rank order : lipid : EA ratio ˃ EA type ˃ lipid type. Optimised transfersomes sustained the release of lidocaine over 24 h. Conclusion Sustained-release, lidocaine-loaded transfersomes were successfully formulated and optimised using a DOE approach, and a new HPLC method for lidocaine analysis was developed and validated.

It is Tuesday, April 2 2019. On this day, like many days, the three of us sat down to answer and craft emails. But on this day, we wrote to each other, responding to a simple question that we began to ponder: “What if we created a peer review journal of academic librarian engagement?”.

Objective Evaluating Health Information Technologies (HITs) can be challenging, but studies are necessary so that the most beneficial interventions can be identified. Our objective was to systematically review the available recommendations for improving the methods used in HIT evaluations. Methods HIT evaluation frameworks were identified from database (MEDLINE, EMBASE, CINAHL) and grey literature searches. Outcome measures included framework recommendations and characteristics. Recommendations were coded and organised using thematic analysis methods. A scoring instrument was used to measure framework quality. Results The search identified 23 frameworks and 272 recommendations. These were organised into five evaluation domains and 42 themes. The themes included recommendations for improving the evaluation of technical aspects of HITs (e.g. describing aspects of HIT functionality) and suggestions for improving the evaluation of complex factors that may influence the overall effects of HITs (e.g. careful reporting of whether the HIT became integrated into existing working patterns). The frameworks were not generally developed in association with healthcare professionals, or with input from patients. The frameworks tended not to have been developed using systematic methods designed to reduce the risk of bias. Discussion HIT evaluations are important but they are challenging to conduct and appraise. This review was conducted using systematic methods enabling the organisation of framework recommendations into key themes. These findings may help investigators to successfully plan, conduct and appraise HIT evaluations. The quality appraisal demonstrated that HIT evaluation research may be improved by using more systematic methods and the involvement of participants from a range of differing backgrounds.

Purpose The aim of this study was to develop novel paclitaxel-loaded proliposome tablet formulations for pulmonary drug delivery. Method Proliposome powder formulations (i.e. F1 – F27) were prepared employing Lactose monohydrate (LMH), Microcrystalline cellulose (MCC) or Starch as a carbohydrate carriers and Soya phosphatidylcholine (SPC), Hydrogenated soya phosphatidylcholine (HSPC) or Dimyristoly phosphatidylcholine (DMPC) as a phospholipid. Proliposome powder formulations were prepared in 1:5, 1:15 or 1:25 w/w lipid phase to carrier ratio (lipid phase; comprising of phospholipid and cholesterol in 1:1 M ratio) and Paclitaxel (PTX) was used as model anticancer drug. Results Based on flowability studies, out of 27 formulations; F3, F6, and F9 formulations were selected as they exhibited an excellent angle of repose (AOR) (17.24 ± 0.43, 16.41 ± 0.52 and 15.16 ± 0.72°), comparatively lower size of vesicles (i.e. 5.35 ± 0.76, 6.27 ± 0.59 and 5.43 ± 0.68 μm) and good compressibility index (14.81 ± 0.36, 15.01 ± 0.35 and 14.56 ± 0.14) via Carr’s index. The selected formulations were reduced into Nano (N) vesicles via probe sonication, followed by spray drying (SD) to get a dry powder of these formulations as F3SDN, F6SDN and F9SDN, and gave high yield (>53%) and exhibited poor to very poor compressibility index values via Carr’s Index. Post tablet manufacturing, F3 tablets formulation showed uniform weight uniformity (129.40 ± 3.85 mg), good crushing strength (14.08 ± 1.95 N), precise tablet thickness (2.33 ± 0.51 mm) and a short disintegration time of 14.35 ± 0.56 min, passing all quality control tests in accordance with British Pharmacopeia (BP). Upon nebulization of F3 tablets formulation, Ultrasonic nebulizer showed better nebulization time (8.75 ± 0.86 min) and high output rate (421.06 ± 7.19 mg/min) when compared to Vibrating mesh nebulizer. PTX-loaded F3 tablet formulations were identified as toxic (60% cell viability) to cancer MRC-5 SV2 cell lines while safe to normal MRC-5 cell lines. Conclusion Overall, in this study LMH was identified as a superior carbohydrate carrier for proliposome tablet manufacturing in a 1:25 w/w lipid to carrier ratio for in-vitro nebulization via Ultrasonic nebulizer.

In an attempt to decrease the dose, anticipated side effects, and the cost of production of glibenclamide, GLC, a potent oral hypoglycemic drug, the enhancement of the dissolution and hence the oral bioavailability were investigated. Adsorption and co-adsorption techniques using carriers having a very large surface area and surface active agents were utilized to enhance the drug dissolution. Moreover, the Langmuir adsorption isotherms were constructed to identify the type and mechanism of adsorption. The optimized formulation showing the highest in vitro release was compressed into mini-tablet to facilitate drug administration to elderly patients and those having swallowing difficulties. The produced mini-tablets were tested for their mechanical strength and in vitro release pattern. In addition, the pharmacodynamic and pharmacokinetic studies in New Zealand rabbits were performed using the optimized mini-tablet formulation. Mini-tablets containing GLC co-adsorbate with Pluronic F-68 and Laponite RD showed 100 ± 1.88% of GLC released after 20 min. Pharmacodynamic studies in rabbits revealed significantly higher (p ≤ 0.05) hypoglycemic effect with the optimized mini-tablets at a lower GLC dose compared to mini-tablets containing the commercial GLC dose. Moreover, pharmacokinetic analysis showed significantly higher (p ≤ 0.05) AUC, Cmax, and shorter Tmax. The optimized mini-tablet formulation showed 1.5-fold enhancement of the oral bioavailability compared to mini-tablets containing untreated GLC. It could be concluded that the co-adsorption technique successfully enhanced the oral bioavailability of GLC. Furthermore, the produced mini-tablets have a higher oral bioavailability with a lower GLC dose, which could offer economic benefit for industry as well as acceptability for patients.

Fast-dissolving oral films (FDFs) provide an alternative approach to increase consumer acceptance by advantage of rapid dissolution and administration without water. Usually, FDFs require taste-masking agents. However, inclusion of these excipients could make developing the formulation a challenging task. Hence, this work employed fused-deposition modeling three-dimensional printing to produce single-layered FDFs (SLFDFs), or multilayered FDFs (MLFDFs) films, with taste-masking layers being separated from drug layer. Filaments were prepared containing polyethylene oxide (PEO) with ibuprofen or paracetamol as model drugs at 60°C. Also, filaments were produced containing polyvinyl alcohol and paracetamol at 130°C. Furthermore, a filament was prepared containing PEO and strawberry powder for taste-masking layer. FDFs were printed at temperatures of 165°C (PEO) or 190°C (polyvinyl alcohol) with plain or mesh designs. High-performance liquid chromatography and mass spectroscopy analysis indicated active ingredient stability during film preparation process. SLFDFs had thicknesses as small as 197 ± 21 μm, and MLFDFs had thicknesses starting from 298 ± 15 μm. Depending on the formulation and design, mesh SLFDFs presented disintegration time as short as 42 ± 7 s, and this was 48 ± 5 s for mesh MLFDFs. SLFDFs showed drug content uniformity in the range of 106.0%-112.4%. In conclusion, this study provides proof-of-concept for the manufacturing of FDFs by using 3D printing.

Weather forecasting is crucial to both the demand and supply sides of electricity systems. Temperature has a great effect on the demand side. Moreover, solar and wind are very promising renewable energy sources and are, thus, important on the supply side. In this paper, a large vector autoregression (VAR) model is built to forecast three important weather variables for 61 cities around the United States. The three variables at all locations are modeled as response variables. Lag terms are used to capture the relationship between observations in adjacent periods and daily and annual seasonality are modeled to consider the correlation between the same periods in adjacent days and years. We estimate the VAR model with 16 years of hourly historical data and use two additional years of data for out-of-sample validation. Forecasts of up to six-hours-ahead are generated with good forecasting performance based on mean absolute error, root mean square error, relative root mean square error, and skill scores. Our VAR model gives forecasts with skill scores that are more than double the skill scores of other forecasting models in the literature. Our model also provides forecasts that outperform persistence forecasts by between $$6\%$$ and $$80\%$$ in terms of mean absolute error. Our results show that the proposed time series approach is appropriate for very short-term forecasting of hourly solar radiation, temperature, and wind speed.

Clays have previously demonstrated potential as drug delivery carriers for the extended release of a variety of drugs. The objective of this study was to develop and characterise drug-containing clays in combination with natural hydrogels for the preparation of lyophilised xerogels. Sulfathiazole (STH) (a hydrophobic model drug) was intercalated within the interlayer spaces of Laponite® RDS (LAP RDS) or refined montmorillonite (MMT) and then mixed with either carageenen 812 (CAR 812) or hydrohydroxy ethyl cellulose (HEC) hydrogels prior to lyophilisation. The resulting xerogels were characterised visually, using differential scanning calorimetry (DSC) and with scanning electron microscopy (SEM). Optimal geo-polymeric wafers contained 1.5% W/W CAR 812 with 2% LAP RDSand 1% W/W intercalated STH. DSC and SEM results indicated the amorphous form of STH was intercalated inLAP RDS within theleafy structure of CAR 812. This xerogel hydrated up to1700% within 40 minutes and released the STH by Higuchikinetic model. Keywords: Polymer; Clay, Intercalation, Xerogel, Wound delivery, Amorphous, Physicochemical characterisation, Polymers, hydrogel, drug delivery, lyophilised wafer.

This paper examines spatial effects on hybrid-electric vehicle (HEV) adoption. This is in contrast to most existing analyses, which concentrate on analyzing socioeconomic factors and demographics. This paper uses a general spatial model to estimate the strength of ‘neighbor effects’ on HEV adoption—namely that each consumer’s HEV-adoption decision can be influenced by the HEV-adoption decisions of geographic neighbors. We use detailed census tract-level demographic data from the 2010 United States Census and the 2012 American Community Survey and vehicle registration data collected by the Ohio Bureau of Motor Vehicles. We find that HEV adoption exhibits significant spatial effects. We further conduct a time-series analysis and show that historical HEV adoption has a spatial effect on future adoption. These results suggest that HEVs may appear in more dense clusters than models that do not consider spatial effects predict.

Understanding the effect of surfactant properties is critical when designing vesicular delivery systems. This review evaluates previous studies to explain the influence of surfactant properties on the behavior of lipid vesicular systems, specifically their size, charge, stability, entrapment efficiency, pharmacokinetics, and pharmacodynamics. Generally, the size of vesicles decreases by increasing the surfactant concentration, carbon chain length, the hydrophilicity of the surfactant head group, and the hydrophilic-lipophilic balance. Increasing surfactant concentration can also lead to an increase in charge, which in turn reduces vesicle aggregation and enhances the stability of the system. The vesicles' entrapment efficiency not only depends on the surfactant properties but also on the encapsulated drug. For example, the encapsulation of a lipophilic drug could be enhanced by using a surfactant with a low hydrophilic-lipophilic balance value. Moreover, the membrane permeability of vesicles depends on the surfactant's carbon chain length and transition temperature. In addition, surfactants have a clear influence on pharmacokinetics and pharmacodynamics such as sustaining drug release, enhancing the circulation time of vesicles, improving targeting and cellular uptake.

Understanding energy use is critical. Although simulation is valuable, such models are simplified abstractions of actual energy systems. The authors present an energy system multimodel implemented with the Language and Platform Independent Steering (LAPIS) computational steering API. They present an adaptable framework for the integration and development of multimodel simulations. This framework enables independent development of component simulations, limits coordination overhead between developers, and allows modularity and flexibility in the overall multimodel simulation. Use case studies demonstrate the capabilities of the multimodel energy system simulation and LAPIS.

The ability of clay minerals to adsorb and desorb drugs, including antibacterial molecules, is an attractive and exciting prospect for healthcare applications. The antibacterial ciprofloxacin was adsorbed onto kaolin, montmorillonite K-10, and Laponite® RD then the subsequent antibacterial activity of the composites formed was confirmed. The effects of time, pH, and CIP concentration were investigated. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy were used to confirm the mechanism of ciprofloxacin adsorption onto the clay minerals. Dispersion pH was the most important variable influencing the adsorption of ciprofloxacin onto the clay minerals and the mechanism of adsorption was confirmed as cation exchange. Adsorption isotherms and application of Langmuir and Freundlich models showed that a ciprofloxacin monolayer was formed at different concentrations on each of the clay minerals tested. Kinetic studies showed that maximal CIP adsorption was achieved within the first hour of adsorption. Antibacterial activity of clay–ciprofloxacin composites against the common skin bacteria Staphylococcus epidermidis and Propionibacterium acnes was demonstrated. This work showed that clay–ciprofloxacin composites are potential delivery systems for ciprofloxacin molecules. As a result, this could make them ideal candidates to take forward for healthcare applications, including the development of novel wound dressings.

This paper presents a model to simulate the electricity demand of a single household consisting of multiple individuals. The total consumption is divided into four main categories, namely cold appliances, heating, ventilation, and air conditioning, lighting, and energy consumed by household members’ activities. The first three components are modeled using engineering physically-based models, while the activity patterns of individuals are modeled using a heterogeneous Markov chain. Using data collected by the U.S. Bureau of Labor Statistics, a case study for an average American household is developed. The data are used to conduct an in-sample validation of the modeled activities and a rigorous statistical validation of the predicted electricity demand against metered data is provided. The results show highly realistic patterns that capture annual and diurnal variations, load fluctuations, and diversity between household configuration, location, and size.

BACKGROUND: Children often need to be administered very small volumes of medicines that are authorised for use in adults. Neonatal drug delivery is particularly challenging, and doses are often immeasurable with the equipment currently available. AIM: To summarise research to date on the accuracy of intravenous and enteral medicine preparation requiring small volumes (

This paper specifies and estimates state-level models of short- and long-term electricity demand in the United States. The short-term model predicts hourly load based on weather and calendar inputs. The long-term model estimates interannual demand, and includes population, prices, and gross state product as predictors. These models are combined to incorporate the short- and long-term trends in electricity consumption when generating forecasts of diurnal patterns into the future. Finally, the authors investigate the effects of short-run price elasticities of demand. The short-term model is shown to be within 95% accuracy of actual levels in out-of-sample tests.

Sustained-release mini-tablets are a potentially suitable for paediatric drug delivery or as multi-particulate dosage forms.To evaluate the potential for developing lipophilic matrix mini-tablets and to assess the effects of Compritol® 888 ATO concentration on drug release from differently sized mini-tablets prepared by direct compression.A formulation comprising theophylline as a model soluble drug, 15% w/w Compritol® 888 ATO as the inert matrix-forming agent, with dibasic dicalcium phosphate anhydrous and lactose as diluents was evaluated by producing 12 mm tablets at a range of compression speeds and forces. The same formulation and further formulations with 25, 35 or 45% w/w Compritol® 888 ATO were evaluated by producing 2, 3 and 4 mm mini-tablets.Drug release from matrix tablets was sustained over a period of 12 hours and release rate varied according to the compression force and speed employed. The rate of drug release from matrix mini-tablets was more rapid and increasing Compritol® 888 ATO concentration resulted in slower release rates. The rate of drug release from matrix mini-tablets was inversely proportional to mini-tablet size (2 mm3 mm4 mm). Drug release from the matrix tablets and mini-tablets followed square-root of time kinetics.Tailored drug release from matrix mini-tablets may achieved by altering the size of mini-tablet or level of Compritol® 888 ATO in the formulation and this may have potential in the development of paediatric formulations or multi-particulate dosage forms.

Ibuprofen (α-methyl-4-(isobutyl)phenylacetic acid) was recrystallised from a range of solvents. Particle morphology, crystallinity, melting points and powder flow properties were evaluated. Additionally, the compaction properties of the ibuprofen control and recrystallised samples were assessed at different compaction forces and speeds, before and after blending with an equal amount of lactose, using a Stylcam® 100R rotary press simulator. Recrystallised ibuprofen samples displayed equal or better tablet strength than the control, whilst ibuprofen recrystallised from acetone had improved flowability and ibuprofen recrystallised from 2-ethoxyethyl acetate exhibited lower levels of elastic energy during compaction. Additionally, when formulated with lactose, recrystallised ibuprofen samples displayed lower punch adhesion levels, particularly at a low compaction force.

Much of the current literature on trade in biofuels is focused on the partial equilibrium welfare effects in the U.S. ethanol sector of potentially distorting policy instruments such as tax credits to blenders and import tariffs (see Elobeid and Tokgoz 2006; de Gorter and Just 2007). However, recent studies by the OECD (2006) and the World Bank (Kojima, Mitchell, and Ward 2007) have expanded the analysis to consider the future prospects for trade in both ethanol and biodiesel, paying particular attention to current production costs across countries and the connection between thresh old prices for crude oil prices and biofuel pro duction costs as well as the land requirements needed to meet the types of biofuel production mandates being implemented in the United States, the European Union (EU), and else where. Two key stylized facts can be gleaned from these latter studies: while increasing crude oil prices have improved the economic viability of say U.S. corn-based ethanol, Brazil continues to have a significant comparative advantage in producing ethanol from sugarcane (OECD 2006; Kojima, Mitchell, and Ward 2007); sec ond, the land requirements necessary to meet targets being set for the proportion of biofu els used in transport fuel consumption show that again Brazil has a clear comparative ad vantage. For example, Brazil only requires 3 % of its agricultural land to meet a 10% share of biofuels in domestic transport fuel consump tion, compared to 30%, 36%, and 72%, re spectively in the United States, Canada, and the E.U. (OECD 2006). This all seems to point to a simple, but rather predictable story of trade in biofuels: in the absence of trade-distorting policy instru ments, Brazil currently has a comparative and maybe even an absolute advantage in produc ing biofuels, based on lower ethanol feedstock costs and relative abundance of agricultural land. Even in the presence of trade distortions, Brazil exported 20% of its production during the 2006-7 harvest season (Kojima, Mitchell, and Ward 2007), and this would increase sub stantially if the United States removed its ethanol import tariff of 54 cents per gallon (Elobeid and Tokgoz 2006). However, the mar gin for competitiveness in biofuels is rather narrow, only 10% of production being traded internationally, of which Brazil accounts for 50% (Kojima, Mitchell, and Ward 2007). This is a static story, though, based on cur rent crop yields as well as existing biofuel production technologies. Consequently, in try ing to analyze the potential for United States comparative advantage in biofuels production, it is important to account for technological innovation that may occur within the next decade, notably in the production of ethanol from cellulosic material. To that end a styl ized trade model is set out in the first part of this article, which allows for the possibil ity that the United States could become a fu ture exporter of biofuels. The model draws on a Heckscher-Ohlin-Ricardo approach origi nally due to Davis (1995), as well as analysis of trade in the presence of external economies (Helpman and Krugman 1985). Given this analysis, the second part of the article is con cerned with the possibility that current U.S. policy toward corn-based ethanol production may actually stymie the potential for future exports, drawing on recent literature analyz ing the infant-industry argument for protec tion (Saure 2007).

The national movement towards progress files, incorporating personal development planning and reflective learning, is supported by lecturers providing effective feedback to their students. Recent technological advances mean that higher education tutors are no longer obliged to return comments in the ‘traditional’ manner, by annotating students' work with red pen. This paper considers some of the options currently available for returning computer-assisted feedback, including the Electronic Feedback freeware. This MS Office application enables tutors to readily synthesise and email feedback reports to students. To further ascertain the value of this software, 169 1st-year Pharmaceutical Science and Pharmacy students completed a questionnaire to gauge their reaction to formative feedback on an extended laboratory report. This included 110 responses from students graded by three tutors who marked work using either handwritten annotations or the Electronic Feedback program. Principle component analysis (PCA) of the Likert scale responses indicates that the identity of the marker did not significantly affect the response of students. However, the type of feedback was a factor that influenced the students' responses, with electronic feedback being rated superior. A Mann-Whitney analysis of the satisfaction ratings (generated by PCA) indicates that four features of the assignment and feedback were considered significantly improved when the software was used to create feedback, namely; markscheme clarity, feedback legibility, information on deficient aspects, and identification of those parts of the work where the student did well. Modern academics face a number of challenges if they wish to return meaningful and timely feedback to students, among them large class sizes and infrequent face-to-face contact. It is pleasing to note, therefore, that assessors reported taking less time to mark when using the software. It is concluded that electronic formative feedback can be returned more quickly and may be used to synthesise relevant feedback that is both fair and balanced.

An updated supply of storage is estimated to reflect recent developments in the literature. This study adds a measure of price variability, specifically implied volatility. It also adds a measure of the call-option value to sell stocks before the end of the storage period, specifically a measure developed by Heaney (2002). The model is estimated for U.S. soybean stocks carried between crop years. A quadratic relationship is found between stocks to use ratio and implied volatility. A statistically significant, inverse, linear relationship is found between the storage-cost–adjusted spread and the estimated call-option value. This finding is consistent with the much debated idea that convenience yield is a return to storage that can offset losses from storage when intertemporal price spreads are negative. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:657–676, 2006

Hypromellose, formerly known as hydroxypropylmethylcellulose (HPMC), is by far the most commonly employed cellulose ether used in the fabrication of hydrophilic matrices. Hypromellose provides the release of a drug in a controlled manner, effectively increasing the duration of release of a drug to prolong its therapeutic effect. This review provides a current insight into hypromellose and its applicability to hydrophilic matrices in order to highlight the basic parameters that affect its performance. Topics covered include the chemical, thermal and mechanical properties of hypromellose, hydration of the polymer matrices, the mechanism of drug release and the influence of tablet geometry on drug-release rate. The inclusion of drug-release modifiers within hypromellose matrices, the effects of dissolution media and the influence of both the external environment and microenvironment pH within the gel matrix on the properties of the polymer are also discussed.

Although academic research on the usefulness of technical analysis is mixed at best, its use remains widespread in commodity markets. Much prior research into technical analysis suffers from data-snooping biases. Using genetic programming, ex ante optimal technical trading strategies are identified. Because they are mechanically generated from simple arithmetic operators, they are free of the data-snooping bias common in technical analysis research. Futures prices from 24 markets are used in rule generation. Rules for only two of the markets are capable of generating profits at the 5% level of significance using out-of-sample data, lending little support for technically based systems. © 2005 Wiley Periodicals, Inc. Jrl Fut Mark 25:643–660, 2005

There has been considerable debate regarding which probability distribution best represents crop yields. This study ranks six yield densities based on their out-of-sample forecasting performance. The forecasting ability for each density was ranked according to its likelihood function value when observed at out-of-sample observations. Results show that a semiparametric model offered by Goodwin and Ker best forecasts county average yields. Copyright 2004, Oxford University Press.

The aim was to enhance the dissolution of lornoxicam (LOR) and to produce mini-tablets with an optimised system to provide a rapid-release multi-particulate formulation. LOR systems were prepared through co-evaporation with either polyethylene glycol 6000 or Pluronic(®) F-68 (PLU) and adsorption onto Neusilin(®) US2 alone or co-adsorption in the presence of different amounts of polysorbate 80. All systems were characterised by FT-IR, differential scanning calorimetry, X-ray diffraction, flowability and dissolution techniques. Mini-tablets were prepared using the system with the optimum dissolution profile and flowability. Tensile strengths, content uniformity and dissolution profiles of the mini-tablets were evaluated. The effects of different excipients and storage conditions on mini-tablet properties were also studied. The optimised rapid-release LOR mini-tablets were further evaluated for their in vivo pharmacokinetic profile. The co-evaporate of LOR with PLU showed significantly faster dissolution and superior flowability and was evaluated together with three directly compressible excipients (Cellactose(®) 80, StarLac(®) (STA) and Emcompress(®)) for mini-tablet formulation. The formulation with STA provided the optimum results in terms of tensile strength, content uniformity and rapid drug release following a 3-month stability study and was selected for further in vivo evaluation. The pharmacokinetic profile indicated the potential of the mini-tablets achieving rapid release and increased absorption of LOR.

The consumption of fibers is associated with many health benefits, such as a reduction of cardiovascular and gastrointestinal diseases, control of body weight, and prevention of diabetes. Despite the widespread use of fiber supplements such as capsules or tablets, there is an almost complete lack of information concerning the technological properties of functional fibers used in nutraceutical formulations. The aim of this work was to characterize the technological properties of citrus fibers necessary for their use as a processing aid in tableting. The results obtained showed that citrus fibers share many properties of other polysaccharides used as tableting excipients, such as thermal behavior and compaction mechanism, together with an appreciable tabletability. However, the most interesting properties resulted from their disintegration power. Citrus fibers behaved in a similar manner to the well-known super disintegrant croscarmellose sodium and resulted to be little susceptible to their concentration, to lubricant type, and lubricant concentration. Thus, this work supports the idea of a potential use of citrus fibers as “active” substances and processing aid in the tableting of nutraceutical products and also as functional excipient in pharmaceutical tablets formulation.

Parenteral administration, specifically the intravenous route, is the most widely used method of drug administration in very ill preterm and term neonates and children and during unconsciousness. In other circumstances, some drugs need to be given parenterally due to instability and enzymatic degradation in the gut, variable oral absorption, the need for rapid onset of action, high or sustained levels not achievable by other routes or to avoid first-pass metabolism and gastrointestinal side effects. Consequently, intravenous, intramuscular and subcutaneous injections are commonly used administration routes.

The preparation of lipophilic matrix tablets for the sustained release of water soluble drugs via direct compression is not always feasible due to poor flow and rapid drug release. The aim was to evaluate the potential for developing sustained-release diclofenac sodium tablets, using Compritol® 888 ATO as a lipid matrix, by a wet granulation technique. The effects of wet granulation method (planetary mixer and fluid-bed) and liquid binder type (HPMC Metolose® 603, 606 or 615) on weight uniformity, tensile strength and release rates were investigated. The influence of compression force and speed during tablet manufacture under simulated rotary press production conditions were also evaluated. Rapid release of diclofenac sodium from directly compressed matrices was observed. A wet granulation technique using different HPMC binders produced free-flowing granules and matrices which released diclofenac sodium in a sustained manner over several hours. When the formulation comprising the lowest viscosity grade HPMC (Metolose® 603) was further evaluated using a laboratory scale fluid-bed system, consistently sized granules with good flowability and matrices with good weight uniformity and tensile strengths were produced. Release rates were consistent over a range of compression speeds and forces indicating the suitability of the formulation for production on a rotary tablet press.

It is well known that ethanol has less energy per unit volume than gasoline. Differences in engine design and fuel characteristics affect the efficiency with which the chemical energy in gasoline and ethanol is converted into mechanical energy, so that the change in fuel economy may not be a linear function of energy content. This study analyzes the fuel economy tests performed by the US Environmental Protection Agency (EPA) on 2007 model year E85-compliant vehicles and finds that the difference in average fuel economy is not statistically different from the differential in energy content.

Congenital myasthenic syndromes are a heterogeneous group of conditions in which muscle weakness resulting from impaired neuromuscular transmission is often present from infancy. One form of congenital myasthenic syndrome is due to a reduction of the number of acetylcholine receptors (AChRs) at the neuromuscular junction. We describe four new cases of AChR deficiency, characterized by a reduction in both miniature endplate potential amplitude and AChR abundance accompanied by elongation of the neuromuscular junction and some decrease in postsynaptic folding. A number of cytoplasmic proteins are normally associated with the postsynaptic membrane and may contribute to the clustering of AChRs at the neuromuscular junction. We therefore investigated the expression of several of these proteins in these AChR-deficiency patients. In each patient, immunolabelling of the neuromuscular junction for rapsyn, dystrophin, beta-dystroglycan and a form of beta-spectrin was strong but that for utrophin was markedly reduced or absent. This suggested that a defect in utrophin expression might underlie the congenital AChR deficiency. However, a reduction in utrophin labelling was also seen in three patients with adult acquired autoimmune myasthenia gravis in whom AChR loss results directly from the extracellular binding of autoantibodies. We conclude that the loss of AChRs in AChR deficiency does not result from the absence of rapsyn or beta-dystroglycan and that reduction of utrophin is probably secondary to the loss of AChRs. The possible role of AChRs and/or utrophin in determining the extent of postsynaptic folding is discussed.

Hypromellose (HPMC) has been previously used to control drug release from mini-tablets. However, owing to poor flow, production of mini-tablets containing high HPMC levels is challenging. Directly compressible (DC) HPMC grades have been developed by Dow Chemical Company.To compare the properties of HPMC DC (METHOCEL™ K4M and K100M) with regular (REG) HPMC grades.Particle size distribution and flowability of HPMC REG and DC were evaluated. 3 mm mini-tablets, containing hydrocortisone or theophylline as model drugs and 40% w/w HPMC DC or REG were produced. Mini-tablets containing HPMC DC grades were manufactured using a rotary press simulator at forces between 2-4 kN and speeds of 5, 10, 15 or 20 rpm. Mini-tablets containing HPMC REG were produced manually.The improved flowability of HPMC DC grades, which have a narrower particle size distribution and larger particle sizes, meant that simulated large scale production of mini-tablets with good weight uniformity (CV 1.79-4.65%) was feasible. It was not possible to automatically manufacture mini-tablets containing HPMC REG due to the poor flowability of the formulations. Drug release from mini-tablets comprising HPMC DC and REG were comparable. Mini-tablets containing HPMC DC illustrated a higher tensile strength compared to mini-tablets made with HPMC REG. Mini-tablets produced with HPMC DC at different compression speeds had similar drug release profiles.Production of extended release mini-tablets was successfully achieved when HPMC DC was used. Drug release rate was not influenced by the different HPMC DC grades (K4M or K100M) or production speed.

Agricultural and food production is fundamentally different than other forms of production in the economy, and the differences require alternate methods of risk management. This chapter reviews the primary tools available to producers for the management of price and quantity risk, including insurance, government programs, and market-based instruments. Each of these tools is explained in both historical context and for how it impacts on market function. Current controversies in policy and markets and marketing are then discussed, as are recent research findings and proposed solutions. Some of the controversies addressed are the impact of speculation, packer ownership of cattle, and planting restrictions for decoupled payments.

Mini-tablets are compact dosage forms, typically 2-3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL™ K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.

Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied.

Embedding a drug in a polymeric matrix in the molecular or dispersed state can enhance or control its rate of dissolution/release from the dosage form to modify its bioavailability or pharmacokinetics. The embedded drug may be dissolved in the polymer, be in a highly dispersed form, or in a stable high-energy state such as its amorphous form. Other materials added to the drug/polymer system may help provide a release and subsequent plasma profile or time-course that optimizes the drug’s action. The thermoplasticity of the polymer is a prerequisite for utility in such matrices. Functionality depends on its nature and level and on the presence and properties of other release-affecting additives. Thermal stability of the drug and compatibility with the other agents is vital. Pharmaceutical textbooks have not traditionally provided detailed accounts of the equipment and technologies used for preparing thermoplastic matrices at industrial scale. Hence, a fulsome account is provided at the start of this chapter. The suitability and properties of the polymeric excipients are also summarized and discussed.

The aim of this study was to evaluate the compaction behavior of a model two-component amorphous spray-dried dispersion system compared with the unprocessed excipients, using simulated rotary tablet press production conditions.In this study, the stabilizing polymer, hypromellose acetate succinate (HPMCAS), was solubilized and spray dried with and without sodium lauryl sulfate (SLS). The impact of compression force and speed on the tabletting process was quantified by means of tablet tensile strength, compaction energy, and Heckel analysis.Addition of the surfactant SLS, spray dried or as a physical mix, reduced the tablet strength. However, a lesser impact on the unprocessed excipients was observed in comparison with the spray-dried excipients. In the presence of 1% (w/w) SLS, tablets displayed a tendency to cap when compressed at higher speeds, supported by high elastic energy values indicating high uniaxial stress upon decompression. In the presence of 3% (w/w) SLS, tablets could not be produced at high speeds. Heckel analysis revealed a greater strain rate sensitivity of HPMCAS when spray dried in the presence of surfactant. Exposure of samples to a range of relative humidities before compaction had no effect on tablet strength.This study has shown that spray drying of HPMCAS in the presence of a surfactant affects the compressibility of the material, resulting in decreased tablet strength, increased elastic deformation, and capping.

The dairy industry in the United States is amidst a long-running trend toward fewer, larger dairy farms. This development has created a backlash in some communities over concerns such as odor, waste management, and environmental degradation. Separately, anaerobic digestion has advanced as a waste management technology that potentially offers solutions to some of these issues, providing odor control and a combustible biogas among other things. These digesters require significant capital investments. Voluntary consumer premiums for the renewable energy produced have been used in some instances as a means to move adoption of such systems toward financial feasibility. This project employed a survey to measure Ohio consumers' willingness to pay a premium for renewable energy produced by anaerobic digesters on dairy farms. Cluster analysis was used to segment consumers by willingness to pay, age, education, income, self-identified political inclination, and a composite variable that served as a proxy for respondents' environmental stewardship. Four distinctive groups emerged from the data. Older, less educated respondents were found to have the least amount of support for digesters on dairy farms, whereas politically liberal, environmentally proactive respondents demonstrated the strongest support. Well-educated, affluent respondents and young respondents fell between these 2 groups. Most large dairy farms are generally met with fairly negative responses from their local communities; in contrast, this research finds some popular support for anaerobic digestion technology. Going forward, establishing a positive link between support for anaerobic digesters and for their use on large dairies could open up a new route for less-contested large dairy farm developments. Evaluation of community demographics could become an important part of finding an optimal location for a large dairy farm.

To be effective as communications or sales tools, documents that are personalized and customized for each customer must be visually appealing and aesthetically pleasing. Producing perhaps millions of unique versions of essentially the same document not only presents challenges to the printing process but also disrupts the standard quality control procedures. The quality of the alignment in each document can easily distinguish professionally looking documents from amateur designs and some computer generated layouts. A multicomponent measure of document alignment and regularity, derived directly from designer knowledge, is developed and presented in computable form. The measure includes: edge quality, page connectivity, grid regularity and alignment statistics. It is clear that these components may have different levels of importance, relevance and acceptability for various document types and classes, thus the proposed measure should always be evaluated against the requirements of the desired class of documents.

There is a significant need for research and development into paediatric medicines. Only a small fraction of the drugs marketed and utilized as therapeutic agents in children have been clinically evaluated. The majority of marketed drugs are either not labelled, or inadequately labelled, for use in paediatric patients. The absence of suitable medicines or critical safety and efficacy information poses significant risks to a particularly vulnerable patient population. However, there are many challenges associated with developing medicines for the paediatric population and this review paper is intended to highlight these. The paediatric population is made up of a wide range of individuals of substantially varied physical size, weight and stage of physiological development. Experimentation on children is considered by many to be unethical, resulting in difficulties in obtaining critical safety data. Clinical trials are subject to detailed scrutiny by the various regulatory bodies who have recently recognized the need for pharmaceutical companies to invest in paediatric medicines. The costs associated with paediatric product development could result in poor or negative return on investment and so incentives have been proposed by the EU and US regulatory bodies. Additionally, some commonly used excipients may be unsuitable for use in children; and some dosage forms may be undesirable to the paediatric population.

Release profiles of aspirin from hypromellose matrices in hydro-ethanolic media were studied. Percent aspirin released increased with increasing levels of ethanol in the dissolution media, correlating with the drug's solubility, however, dose dumping of aspirin did not occur. An initial rapid release was observed in media comprising 40% ethanol. Release in these conditions was considered to be both erosion and diffusion-mediated, in contrast to the release in 0, 10, 20 and 30% ethanol media, where erosion-controlled release dominated. Image analysis of matrix swelling indicated a slower initial interaction between ethanol and hypromellose accounting for the initial rapid release. Cloud point studies suggested that ethanol retarded hydration of the polymer.

The sticking of a model ibuprofen-lactose formulation with respect to compaction force, punch tip geometry and punch tip embossment was assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Three sets of ‘normal’ concave punches were used to evaluate the influence of punch curvature and diameter. The punches were 10, 11 and 12 mm in diameter, respectively. The 10-mm punch was embossed with a letter ‘A’ logo to assess the influence of an embossment on sticking. Flat-faced punches (12.5 mm) were used for comparison with the concave tooling. Surface profiles (Taylor Hobson Talysurf 120) of the upper punch faces were obtained to evaluate the surface quality of the tooling used. Following compaction, ibuprofen attached to the upper punch face was quantified by spectroscopy. Increasing punch curvature from flat-faced punches to concave decreased sticking. Altering punch diameter of the concave punches had no effect on sticking when expressed as μg mm−2. The embossed letter ‘A’ logo increased sticking considerably owing to the probable concentration of shear stresses at the lateral faces of the embossed logo.

A model formulation, comprising ibuprofen and direct compression lactose (Tablettose 80) was used to assess the influence of two lubricants, magnesium stearate and stearic acid, on punch tip adherence. Lubricant concentrations were varied from 0.25% to 2% w/w. Formulations in the presence and absence of 0.5% w/w colloidal silica (Aerosil 200) were examined, to assess the influence of the glidant on the anti-adherent effects of the lubricants. Differential scanning calorimetry (DSC) was used to examine the effect of the lubricants on the melting temperature of ibuprofen. Tablets were compacted using a single punch tablet press at 10 kN using hard chrome-plated punches or at 40 kN using uncoated steel punches, tooling was 12.5-mm diameter in each case. The upper punch faces were characterized by obtaining Taylor Hobson Talysurf surface profiles. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. At low concentrations of each lubricant, the levels of sticking observed were similar. Whilst sticking increased at magnesium stearate concentrations above 1%, sticking with stearic acid remained relatively constant at all concentrations. DSC revealed that the melting temperature of ibuprofen was lowered by the formation of eutectic mixtures with both lubricants. However, the onset temperature of melting and melting point were lowered to a greater extent with magnesium stearate compared with stearic acid. When using uncoated tooling at 40 kN, the deleterious effects of magnesium stearate on the tensile strength of the tablets also contributed to sticking. When using chrome-plated punches at 10 kN, the tensile strength reduction by the presence of magnesium stearate was less pronounced, as was the level of sticking.

A six-state USDA-IFAFS funded research project (Aerial Pollutant Emissions from Confined Animal Buildings, APECAB) was conducted with the purpose of determining hydrogen sulfide, ammonia, PM10, and odor emission rates from selected swine and poultry housing systems. An important aspect of emission studies is to be able to measure the mass flow rate of air through the housing system. For this research project, the decision was made to study only fan ventilated buildings due to the difficulty in estimated mass flow rates through naturally ventilated buildings. This paper highlights the various techniques used throughout the study to determine mass flow rate through fan ventilated swine and poultry housing systems.

The sticking of three model ibuprofen–lactose formulations with respect to compaction force and the surface quality of the upper punch were assessed. Compaction was performed at 10, 25 or 40 kN using an instrumented single-punch tablet press. Two sets of 12.5-mm flat-faced punches were used to evaluate the influence of surface quality. A third set of chrome-plated tooling was also used. Surface profiles (Taylor Hobson Talysurf 120) of the normal tooling upper punches indicated a large difference in quality. The punches were subsequently classified as old (Ra = 0.33 μm) or new (Ra = 0.04 μm) where Ra is the mean of all positive deviations from zero. Surface profiles of sample tablets were also obtained. Following compaction, ibuprofen attached to the face was quantified by spectroscopy. Punch surface roughness, compaction force and the blend composition were all significant factors contributing to sticking. Chrome plating of punch faces increased sticking at a low compaction force but decreased sticking at higher forces. Surface roughness of the tablets did not correlate with the corresponding data for sticking, indicating that this is not a suitable method of quantifying sticking.

We welcome the comment by Ramirez and McDonald (RM) and view the comment as a proposed extension of our 2004 paper (Norwood, Roberts, and Lusk). There is little to disagree within what they have to say, so in this reply we revisit the main issues of our 2004 paper with particular attention to how RM's comment relates to our findings. Yield models are primarily used to forecast the probability distribution of future yields (e.g., for setting crop insurance rates). Thus, yield models should primarily be judged on their forecasting ability, and the main purpose of our paper was "to develop a method for evaluating crop yield distributions by determining how well they describe the distribution of out-of-sample yields" (p. 1032). This method is referred to as out-of-sample-log-likelihood function (OSLLF) approach. Nowhere do RM criticize this method. Later in the paper we illustrate the OSLLF method by comparing six yield distributions. It is here where RM add to the interpretation of our results. Let us disaggregate any yield model into three components: the equations describing (a) expected yield, (b) yield variance, and (c) the remaining moments. These are referred to as the mean equation, variance equation, and conditional distribution. A yield model's forecasting ability will depend on how well each component approximates the true yield generating process and the model's degrees of freedom. While a model containing more parameters may better approximate the true yield distribution, due to its smaller degrees of freedom that erode statistical information, it may provide inferior yield predictions. The OSLLF provides a useful method of comparing models that differ in their degrees of freedom. To demonstrate the OSLLF method in our 2004 paper, we chose six yield models on the basis of prior AJAE articles. Our intention was to match the past articles exactly, but because of data limitations and other c ncerns, some modifications were made. The yield models differed in their mean equation, variance equation, and conditional distribution. Using the OSLLF method, we ranked the six models according to their forecasting ability. It is important to note that we ranked yield models, which are combinations of the mean equation, variance equation, and conditional distributions; we did not rank specific conditional distributions.