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Historically, Cisco Coregonus artedi and Lake Whitefish Coregonus clupeaformis were abundant throughout the Laurentian Great Lakes, but overharvest, habitat degradation, and interactions with exotic species caused most populations to collapse by the mid-1900s. Strict commercial fishery regulations and improved environmental and ecological conditions allowed Cisco to partially recover only in Lake Superior, whereas Lake Whitefish recovered in all the upper Great Lakes (Superior, Michigan, and Huron). The differential responses of Cisco and Lake Whitefish to improved environmental and ecological conditions in lakes Michigan and Huron have led to questions about potential negative interactions between these species. To provide context for fishery managers, we tested for positive and negative correlations between historical (1929–1970) Cisco and Lake Whitefish commercial gill net catch per effort (CPE; kg/km of net) at a variety of spatial scales in Michigan waters of the upper Great Lakes. The three best-fit spatial models—LAKEWIDE, REGIONAL 10, and SIMPLE—all had similar levels of support (scaled second-order Akaike Information Criterion < 3.0), and we used these models to determine whether there was a significant correlation between Cisco and Lake Whitefish CPE (positive and negative). There was either no correlation between Cisco and Lake Whitefish CPE or a positive correlation for most (12 of 13) pairwise (Cisco–Lake Whitefish) comparisons. We identified no strong positive or negative correlations in the lakewide (LAKEWIDE) or reduced (SIMPLE) models. In the regional model (REGIONAL 10), we identified strong and positive correlations between Cisco and Lake Whitefish CPE in two regions (ρ = 0.59–0.71) and a weak negative correlation in one region (ρ = −0.45). Collectively, our findings suggest that Cisco and Lake Whitefish CPE were largely independent of each other; thus, these species likely did not interact to the detriment of one another in Michigan waters of the upper Great Lakes during 1929–1970.

Background:Boron is unusual to organic chemists, yet boron interacts greatly with organic biochemicals and has considerable bioactivity, especially as an antifungal and insecticide. The bestknown bioactive boron compounds are boric acid, its salt borax, and the closely related boronic acids. A newcomer is tavaborole (trade name Kerydin), recently developed and approved in 2014 for topical treatment of onychomycosis, a fungal infection of nails and the nail bed. It is timely to review the literature and explore the way in which these compounds may work.Methods:The focus of this review is to examine peer-reviewed literature relating to boric acid, boronic acid and tavaborole, the most bioactive boron-containing compounds, and the evidence for their proposed mechanism of antifungal action. In parallel with the literature, we have examined the fungistatic effects of boric acid on yeast.Results:All three compounds are reported to inhibit protein synthesis but their mechanism of action may differ. Chemistry studies indicate an interaction of boric acid with ribose and ribose-containing moieties such as NAD. In this review, we discuss the activity of boric acid and use both tavaborole and the boronic acids to exemplify the similar underlying mechanisms used. As there is a push to develop new antimicrobials, we demonstrate that boric acid’s fungistatic effect is alleviated with ribose, NAD and tryptophan.Conclusion:We speculate that boric acid inhibits yeast growth by disrupting tryptophan synthesis as well as downstream NAD, a rate limiting co-enzyme, essential for cellular function.

From an analytical chemistry standpoint, determining the chemical attribution signatures (CAS) of synthetic reaction mixtures is an impurity profiling exercise. Identifying and understanding the impurity profile and CAS of these chemical agents would allow them to be exploited for chemical forensic information, such as how a particular chemical agent was synthesised. Being able to determine the synthetic route used to make a chemical agent allows for the possibility of batches of the agent, and individual incidents using that agent, to be forensically linked. This information is of particular benefit to agencies investigating the nefarious and illicit use of chemical agents. One such chemical agent of interest to law enforcement and national security agencies is fentanyl. In this study two acylation methods for the final step of fentanyl production, herein termed the Janssen and Siegfried methods, were investigated by liquid chromatography- high resolution mass spectrometry (LC-HRMS) and multivariate statistical analysis (MVA). From these data, fifty-five chemical impurities were identified. Of these, ten were specific CAS for the Janssen method, and five for the Siegfried method. Additionally, analytical data from four different literature methods for production of the fentanyl precursor 4-anilino-N-phenethylpiperidine (ANPP), were compared to the results obtained from the method of production (Valdez) used in this study. Comparison of the LC-HRMS data for these five methods allowed for four Valdez specific impurities to be identified. These may be useful CAS for the Valdez method of ANPP production.

First-year undergraduate classes present challenges in teaching as they usually have high student enrolment numbers and students studying across a range of higher education programs that require a fundamental understanding of knowledge that is not perceived in their area of study. This provides a challenge in terms of engaging and maintaining student interest, primarily because students do not recognize the application of knowledge to their field of study. The challenge is to contextualize the content for the range of student cohorts within the one course. This is a common issue within many of the programs offered at RMIT University, Melbourne, Australia. The teaching pedagogy and learning design pattern developed address the implementation of activities that incorporate the flexible delivery of content, including online media-rich interactive learning via the creation of short videos, to illustrate the direct application and relevance of the content and thereby capture student interest and increase their...

High-field Nuclear Magnetic Resonance (NMR) spectroscopy combined with multivariate analysis techniques have been used extensively in several fields particularly, metabolomics and food quality assessment. In contrast, low-field Fourier transform NMR instruments are a relatively new analytical platform and recent studies have shown its potential application for forensic narcotic identification. In this study Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) were applied on spectra data from both low-field (43 MHz) and high-field (300 MHz) NMR of two key precursors to fentanyl, N-phenethyl-4-piperidone (NPP) and 4-anilino-N-phenethylpiperidine (ANPP). Three different methods were employed for the synthesis of these two precursors – the Siegfried, Valdez and One-Pot methods. The application of low-field NMR spectroscopy combined with multivariate analysis allowed successful classification of fentanyl precursors, NPP and ANPP, based on each synthetic method’s unique impurity profile. This approach supports the possibility of low-field NMR being employed by law enforcement for forensic attribution of clandestine fentanyl and its precursors to a specific synthetic method.

Background Patients with painful varicose veins and venous insufficiency can be treated by eliminating axial reflux only or by eliminating axial reflux plus phlebectomy with transilluminated powered phlebectomy. This study was undertaken with the aim of determining and improving signs and symptoms of venous disease (measured by venous clinical severity score) and complications (by routine surveillance ultrasound and long-term post-operative follow up) for each treatment strategy. Methods We performed a retrospective evaluation of prospectively collected data from 979 limbs undergoing procedures for significant varicose veins and venous insufficiency from March 2008 until June 2014 performed at a single tertiary referral hospital. Patient demographics, Clinical Etiology Anatomy and Pathophysiology classification, venous clinical severity scores pre- and post-procedure, treatment chosen, and peri-operative complications were collected; descriptive statistics were calculated and unadjusted surgical outcomes for patients stratified by the procedure performed. Multivariable logistic regression was used to evaluate the relationship between procedure type and thrombotic complications after adjusting for patient characteristics, severity of disease, pre-operative anticoagulation, and post-operative compression. Result Venous clinical severity scores improved more with radiofrequency ablation + transilluminated powered phlebectomy as compared to radiofrequency ablation alone (3.8 ± 3.4 vs. 3.2 ± 3.1, p = 0.018). Regarding deep venous thrombosis, there was no significant difference between radiofrequency ablation + transilluminated powered phlebectomy vs. radiofrequency ablation alone. There was no statistical difference in asymptomatic endovenous heat-induced thrombosis or infection, although there were slightly more hematomas and cases of asymptomatic superficial thrombophlebitis with combined therapy. On multivariable analysis, only procedure type predicted thrombotic complications. Conclusion Ablation of axial reflux plus transilluminated powered phlebectomy produces improved outcomes as measured by venous clinical severity score, with slight increases in minor post-operative complications and should be strongly considered as initial therapy when patients present with significant symptomatic varicose veins and superficial venous insufficiency. Implementation of a standardized thromboprophylaxis protocol with individual risk assessment results in few significant thrombotic complications amongst high-risk patients, thus potentially obviating the need for routine post-operative duplex.

A novel, solution-processable non-fullerene electron acceptor, 6,6′-((9-(heptadecan-9-yl)-9H-carbazole-2,7-diyl)bis(thiophene-5,2-diyl))bis(2,5-bis(2-ethylhexyl)-3-(thiophen-2-yl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione) (coded as N7), based on central carbazole and terminal diketopyrrolopyrrole building blocks was designed, synthesized and characterized. N7 displayed excellent solubility, thanks to its design allowing incorporation of numerous lipophilic chains, thermal stability, and afforded a 2.30% power conversion efficiency with a high open-circuit voltage (1.17 V) when tested with the conventional donor polymer poly(3-hexylthiophene) in solution-processable bulk-heterojunction devices. To our knowledge, not only is N7 the first reported chromophore based on carbazole and diketopyrrolopyrrole functionalities but the open-circuit voltage reported here is among the highest values for a single junction bulk-heterojunction device that has been fabricated using a simple device architecture, with reproducible outcomes and with no special treatment.

Since human health benefits are influenced by diets and lifestyle, the dietary intake and body–brain interactions of phytochemicals which are abundant in fruits, berries, vegetables, herbs, and in beverages are a promising avenue and resource that can provide dietary intervention and protection strategies against Alzheimer’s disease, Parkinson disease, Huntington disease, and Amyotrophic Lateral Sclerosis dementia diseases. The manipulation of the molecular mechanisms and metabolic processes of food consumption occurring in body and brain can direct, determine, and provide new strategies of how to optimize and select dietary constituents that may sustainably provide generic benefits for neurons to defend against insults and damage, and sustain mental fitness against all neurodegenerative diseases. This chapter provides a perspective of the molecular episodes of dietary phytochemicals including polyphenols, brain foods/beverages, and herbs that can be used and directed towards providing health-sustaining interventions against protein misfolding-neurodegenerative and dementia disorders.

The synthesis and olfactory properties of a series of 2-substituted and 2,3-annulated 1,4-dioxepan-6-ones is reported. By Williamson etherification with 3-chloro-2-(chloromethyl)prop-1-ene (6) and subsequent Katsuki-Sharpless oxidation, 1,4-dioxepan-6-one (8a) and its 2-methyl (8b), 2-propyl (8c), 2-isobutyl (8d), and 2,2,3,3-tetramethyl derivative (8e), as well as four 2,3-annulated 1,4-dioxepan-6-ones 8h, 8i, 8j, and 8k were synthesised. By etherification with ethyl diazoacetate and subsequent Dieckmann cyclisation, (5aS,9aS)-9-bromo- and 9-iodo-5a,6,7,9a-tetrahydro-2H-benzo[b][1,4]dioxepin-3(4H)-one (8f/g) as well as a 2,3-annulated derivative 8m from (+)-limonene were prepared. 2-Propyl-1,4-dioxepan-6-one (8c) was discovered to have a green floral odour with anisic and cinnamic nuances, which could be rationalised by a superposition analysis. The olfactory properties of the 1,4-dioxepan-6-ones synthesised underline the crucial importance of a benzenoid ring system for marine odorants.

As part of our research exploring the influence of molecular variations of Calone 1951® on marine fragrance performance, we report the synthesis, crystal structures, and olfactory analysis of the first saturated benzodioxepinone analogues. By substitution of the aromatic moiety of the benzodioxepinone fragrance molecule with a saturated ring counterpart, we endeavoured to discover the molecular interactions of the aromatic and aliphatic rings with fragrance receptor sites, and also to shed light on any potential chiral interactions occurring within the receptor. Our results showed that an aromatic ring system is necessary for binding to the marine odour receptor(s), and that the addition of an alkene or methyl substituent has little effect on the low receptor affinity. However, a weak marine odour character was found for the 6-methyl saturated derivatives, which could possibly be explained by superposition analysis of the respective structures, which were derived from X-ray coordinates.

Historically, the Cisco Coregonus artedi was abundant throughout the Great Lakes basin, but anthropogenic influences caused the collapse of stocks during the mid-1900s, and fishery managers are currently exploring options for restoration. To increase understanding of biotic and abiotic factors influencing Cisco recruitment dynamics throughout the Great Lakes, we used Ricker stock–recruitment models with rearing-habitat-weighted indices of recruitment and adult spawning stock size in Lake Superior to identify and quantify (1) the appropriate spatial scale for modeling age-1 recruitment dynamics and (2) the effects of biotic and abiotic factors on age-1 recruitment dynamics within the regions identified for modeling. Cisco recruitment variation in Lake Superior was best described by a regional model with separate stock–recruitment relationships for western, southern, eastern, and northern regions. The spatial scale for modeling was approximately 260 km. Age-1 recruitment was negatively correlated w...

Alkanes are a noninvasive method to estimate dry matter intake (DMI) of grazing herbivores. Other cuticular wax components such as long chain fatty alcohols (LCOH) have been used for estimation of diet composition of ruminants eating mixed diets. This study estimated diet composition using n-alkanes and LCOH and estimated DMI using naturally occurring and dosed n-alkanes. Beef steers (Bos taurus) (16 mo. old, 358 ± 9 kg) grazing vegetative adjacent monocultures of tall fescue (Festuca arundinacea Schreb.) and alfalfa (Medicago sativa L. subsp. sativa) were used in this study, which also evaluated diet preference. The LCOH (C 26 , C 28 , and C 30 ) added additional characterization of the forages, but diet composition estimates were not different (P ≥ 0.22) than when estimated using four n-alkanes (C 27 , C 29 , C 31 , and C 33 ). Diet composition estimation indicated that steers consumed similar (P = 0.13) diets of 79 and 70% alfalfa in Year 1 and Year 2, respectively, corresponding to previous work showing a partial preference for legumes. Dry matter intake in Year 2 was lower (P = 0.0002, 4.7 kg d –1 ) than Year 1 (9.2 kg d –1 ), likely due to hot weather in Year 2. This study suggests that if n-alkane profi les of the forages being grazed are distinct, the additional analysis needed to determine LCOH concentrations may not be necessary. Analyzing preliminary forage and fecal samples for n-alkanes to estimate diet composition could reduce labor and expenses by eliminating additional laboratory analyses.

The cisco Coregonus artedi was once the most abundant fish species in the Great Lakes, but currently cisco populations are greatly reduced and management agencies are attempting to restore the species throughout the basin. To increase understanding of the spatial scale at which density-independent and density-dependent factors influence cisco recruitment dynamics in the Great Lakes, we used a Ricker stock–recruitment model to identify and quantify the appropriate spatial scale for modeling age-1 cisco recruitment dynamics in Lake Superior. We found that the recruitment variation of ciscoes in Lake Superior was best described by a five-parameter regional model with separate stock–recruitment relationships for the western, southern, eastern, and northern regions. The spatial scale for modeling was about 260 km (range = 230–290 km). We also found that the density-independent recruitment rate and the rate of compensatory density dependence varied among regions at different rates. The density-independ...

Domestic ruminants select a mixed diet when grazing heterogeneous pastures. Adjacent monocultures allow diet preference to be evaluated without certain constraints that could infl uence diet selection; however, few forage species have been evaluated. Adjacent monocultures of tall fescue (Festuca arundinacea Schreb.) and alfalfa (Medicago sativa L. ssp. sativa) were used to test the theories that selection of mixed diets is infl uenced by a plant’s “novelty,” and that regardless of forage species, cattle will have a partial preference for legumes over grasses. Cattle without previous experience eating alfalfa spent 78% of total grazing time eating alfalfa, whereas after having experience grazing alfalfa they spent less (P = 0.04) time grazing alfalfa (72%). Overall, proportion of the day spent grazing was less (P = 0.001) when alfalfa was novel (40%) than when steers were experienced with both forages (46%). Proportion of the day spent idling was greater (P < 0.001) when alfalfa was novel (35%) than when both forages were familiar (26%). The proportion of grazing time in alfalfa was greater (P = 0.02) in the afternoon (76.8%) than in the morning (72.1%), differing from previous studies that reported a decline in legume preference over the day with an increased grass preference in the afternoon. Application of adjacent monocultures in production systems would benefi t from additional research on performance of cattle grazing in this paddock arrangement.

We evaluate prairie plant community variation in a matrix of restoration treatments in the south Puget Lowland, WA. Native and exotic plant community diversity and composition were measured across areas that differed in burning history and grass-specific herbicide application, having received one to several treatments since 2002. All plots were also variable in historical proximity to a key invasive exotic species (Cytisus scoparius - Scotch broom), a nitrogen-fixing shrub. Three trends were readily apparent from our data: 1) total plant species richness was higher following a prescribed fire. This trend was associated with increases in both native and exotic plants; 2) areas treated with a grass-specific herbicide generally had lower exotic and higher native cover; and 3) using a combination of GIS modeling and community analysis, we found that historical proximity to C. scoparius across all treatment areas was associated with suppressed native species richness. In fact, the magnitude of the effect of historical proximity to C. scoparius was as large as the differences among fire treatment areas. These data suggest that restoration treatments such as fire and herbicide application affect species richness and diversity in prairies, but the changes were neither rapid nor large. Further, exotic species legacies may interact with treatment effects to variably alter restoration outcomes.

Adjacent forage monocultures are a valuable tool to study the diet preference of grazing animals. Previous research has suggested that cattle will exhibit a partial preference for a legume over a grass regardless of forage species. The objective of this study was to determine if beef steers have a partial preference for alfalfa (Medicago sativa L. subsp. sativa) over tall fescue (Festuca arundinacea Schreb.). These forages have not been evaluated previously as adjacent monocultures. Behavior data recorders, global positioning system (GPS), and pedometers were used to evaluate grazing behavior and diet preference of beef steers grazing tall fescue monocultures or adjacent monocultures of tall fescue and alfalfa at proportions (by ground area) of 50:50, 25:75, and 75:25. Steers exhibited a partial preference for alfalfa, grazing it for 61 to 65% of the time regardless of the proportion offered. A diurnal pattern of preference was not observed. Steers grazing tall fescue monocultures spent more time ruminating (p = 0.02) and tended to graze less time (p = 0.06) than steers in adjacent monoculture treatments. Time spent idling, number of prehensions and mastications, and bite rate were similar (p > 0.05) among treatments. Steers grazing tall fescue monocultures spent less time standing, more time lying, were less active, and took fewer steps (p ≤ 0.05) than steers in adjacent monoculture treatments. These results support the proposal that cattle have a partial preference for legumes over grasses.

A 45 T Hybrid Magnet System is being developed at the Nijmegen High Field Magnet Laboratory as part of the Nijmegen Center for Advanced Spectroscopy. The 45 T Hybrid Magnet System will be used in combination with far-infra-red light produced by a Free Electron Laser under construction directly adjacent to the High Field Magnet Laboratory. The superconducting outsert magnet will consist of three CICC coils wound on a single coil form, using Nb$_{3}$Sn strands. A test program for strand and cable qualification is underway. The CICC will carry 13 kA and the coils will produce 12 T on axis field in a 600 mm warm bore. The nominal operating temperature will be 4.5 K maintained with forced-flow supercritical helium. The insert magnet will produce 33 T at 40 kA in a 32 mm bore consuming 20 MW, and will consist of four coils. The insert magnet will be galvanically and mechanically isolated from the outsert magnet. Complete system availability for users is expected in 2014. In this paper we will report on the conceptual design of the 45 T Hybrid Magnet System.

Ruminants grazing mixed-species pastures face many choices, including when and where to graze and how much herbage to consume. These choices affect not only the nutritional status of the animal, but also sward composition and nutritive value through selective defoliation. Limited research has been conducted in the area of dietary selection and preference, most of which has been limited to simple model systems often involving a choice between only two herbage species. Although these studies have provided a vital tool to allow understanding of the fundamental principles of foraging behavior, in reality, grazing ruminants are faced with more complex situations. Understanding and managing animal preferences in mixed swards and thereby altering dietary selection can result in greater primary (plant) and secondary (animal) productivity. Key issues to improve this understanding include a better linking of behavioral and nutritional studies, a better understanding of the genetic factors influencing diet selection, and the development of more explicit spatial models of foraging behavior that incorporate multiple scales of decision making. This article, as part of a set of synthesis articles, reviews the current state of knowledge and research methodologies related to diet selection of grazing domestic ruminants with particular reference to improved temperate grazing environments, including how well we understand each part of the complex decision-making process a grazing ruminant faces, the links with primary and secondary productivity, and developments in methodologies. Finally, we identify key areas where knowledge is lacking and further research is urgently required.

Diet selection, live-weight changes and productivity per hectare of two breeds of goats (Cashmere and local Celtiberic) managed in natural vegetation dominated by heather, and the effect of stocking rate (high or low) in the Cashmere breed, were studied during four grazing seasons. Breed had a significant (P 0.05) between high ( - 0.6 kg/ha) and low stocking rate treatments (4.1 kg/ha). However it was significantly (P

The importance of plant species diversity on performance of livestock grazing temperate region pastures is summarized in this review. As livestock producers seek less capital-intensive production systems, emphasis is redirected toward low-input pasture systems that rely on complex species mixtures to produce forage. Increased plant species diversity has been linked to improvements in ecosystem function. While it is recognized that grazing management can have a profound impact on sward composition, which in turn can affect grazing behavior and animal performance, the effects of increased plant species diversity on animal productivity (and vice versa) have not been well explored. This review addresses mechanisms by which grazing livestock alter cool-season plant species diversity, mechanisms of diet choice, effects of plant species diversity on animal performance, and implications to sustainable domestic livestock grazing systems. We review evidence for these effects at one trophic level, that of grazing livestock in agroeco-systems. While grazing behavior research conducted during the last several decades has led to advances in the understanding of plant-animal interactions, improved knowledge of these interactions is crucial for predicting animal performance. Also important is the evaluation of the impact of grazing livestock on mixed sward dynamics. This knowledge will lead to new opportunities to develop environmentally and economically sustainable grazing systems.

The first saturated benzodioxepinone analogues of Calone 1951 ®, an important artificial fragrance, are synthesized via two different pathways.

Dynamic retirement glidepaths evolve over time based on some measure such as the retiree's funded status or current market valuations. Conversely, static glidepaths are fixed at a starting point and selected under the assumption that they will not change. In practice, new static glidepaths may be derived periodically making them more flexible. The optimal static retirement glidepath would be the one that performs better than all others with respect to some metric. When systematic withdrawals are made from a retirement portfolio, glidepaths are often assessed via the probability of ruin (or success). Our goal here is to derive the optimal static glidepath with respect to this metric. It is a result new to the literature and the shape will be of special interest to retirees, financial advisors, retirement researchers, and target-date fund providers., Comment: Fully documented source code from a C++ implementation is included in the attached proofs appendix

Lognormal random variables appear naturally in many engineering disciplines, including wireless communications, reliability theory, and finance. So, too, does the sum of (correlated) lognormal random variables. Unfortunately, no closed form probability distribution exists for such a sum, and it requires approximation. Some approximation methods date back over 80 years and most take one of two approaches, either: 1) an approximate probability distribution is derived mathematically, or 2) the sum is approximated by a single lognormal random variable. In this research, we take the latter approach and review a fairly recent approximation procedure proposed by Mehta, Wu, Molisch, and Zhang (2007), then implement it using C++. The result is applied to a discrete time model commonly encountered within the field of financial economics., Comment: Fully documented source code is included

Background Opioids like morphine and heroin induce mast cell degranulation in vitro. The release of mast cell mediators like histamine and tryptase may lead to allergic symptoms. In this study it was investigated whether mast cell mediator release also occurs in vivo in addicted patients who participated in a heroin on medical prescription trial, and were under treatment with large doses of heroin in combination with methadone. Method Plasma levels of tryptase, a specific marker for mast cell degranulation, were measured by immuno-assay at baseline and 60 min after heroin administration. Heroin was administered either by intravenous injection (11 subjects) or by inhalation (nine subjects). Single heroin doses varied from 200 to 450 mg. Besides tryptase, the plasma concentrations of heroin, its metabolite morphine and methadone were measured. Results After heroin injection, the mean tryptase plasma concentration increased dose dependently by on average 23.1% (95% CI 14.6–31.6%). After heroin inhalation, no tryptase release was observed. Heroin and morphine peak plasma concentrations were 3–5 times greater in heroin injectors than in inhalers. In heroin injectors, tryptase levels were related to morphine peak concentrations, but not to heroin concentrations. Tryptase plasma concentrations were not related to methadone levels. Mild allergic reactions were reported in five cases after intravenous heroin use, but not after inhalation. Conclusion This study revealed that mast cell mediator tryptase concentrations increase after intravenous heroin injection in chronic opioid users, but not after heroin inhalation. This may be explained by the higher C max levels of metabolite morphine that were achieved after injection than after inhalation. Although statistical significance was reached, the degree of mast cell degranulation after intravenous injection of heroin was mild, and did not lead to clinically relevant side effects in this group of opioid-tolerant subjects.

We present the final design of a 50 mm bore 31+ T Florida-Bitter type resistive magnet using a new shape for the cooling slots. The new shape is like the bow of a boat and effectively smears out stress peaks that usually occur near the sides of cooling slots in previously designed Bitter magnets. Thus peak stress reduction of approximately 20% is obtained. The four-sub-coil magnet will produce 31.2 T at a power dissipation of 17.7 MW, and it will be the most efficient magnet in its class. The three innermost sub coils will be used as an insert to our 8 T Hybrid outsert, providing 30 T continuously at only 9 MW of power

BACKGROUND: In several European countries and in Canada, clinical trials are being conducted in which heroin-addicted patients are treated with pharmaceutically prepared heroin in order to reduce the destructive behaviour that is so often associated with this drug. OBJECTIVE: To develop an integrated population pharmacokinetic model for heroin (diamorphine) and its pharmacodynamically active metabolites 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide. Additionally, the influence on heroin pharmacokinetics of several covariates that are typical for this population was determined. METHOD: Plasma concentration data from 106 heroin-dependent patients in The Netherlands (74 heroin inhalers and 32 injectors) were obtained. The 'chasing the dragon' technique was used for inhalation, in which the fumes of heroin base, heated on aluminum foil, were inhaled. Heroin doses varied between 66 and 450 mg. Heroin, 6-acetylmorphine and morphine data were fitted simultaneously using sequential two-compartment models. Morphine-3-glucuronide and morphine-6-glucuronide data were fitted separately to one-compartment models. All data analysis was performed using nonlinear mixed-effect modelling. RESULTS: The bioavailability of inhaled heroin was estimated to be 53% (95% CI 43.7, 62.3). The terminal half-lives of heroin and 6-acetylmorphine were estimated to be 7.6 and 21.8 minutes, respectively. The clearances of morphine and the morphine-glucuronides were estimated to be 73.6 L/h (95% CI 62.8, 84.4) and between 6 and 10 L/h, respectively. The terminal half-life of 6-acetylmorphine was 13% lower in cocaine users (p < 0.05). No other significant relationships between covariates and pharmacokinetic parameters were discovered. CONCLUSIONS: Pharmacokinetic parameters of heroin and its five major metabolites were assessed simultaneously in one integrated model. Covariate analyses revealed that sex, bodyweight, benzodiazepine use and creatinine clearance (>60 mL/min) do not need to be taken into account in the medical prescription of pharmaceutically prepared heroin for the treatment of heroin dependency

A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to creatinine clearance. After heroin administration, the reaction time was significantly prolonged with 28+/-5.3 msec. in injecting and 13+/-4.9 msec. in inhaling patients. Cardiovascular changes were only mild after heroin administration. Craving-scores declined immediately after heroin administration in both administration groups. Subjective heroin effect was rated more positively in heroin inhaling than in injecting patients, despite the lower C(max) levels following heroin inhalation. In both groups, in this blinded study heroin dose increments were more appreciated than dose reductions. Increments of 50% of the regular heroin dose did not cause any serious side effect.

Electronic animal identification was used to register when sheep moved from one place to another. Non-return gates were used to control the direction of travel of the sheep past electronic identification antennas at the boundary between two areas. A personal computer program was written to control the network of identification readers and to log the ID data together with time stamps of when the IDs were captured. This allowed automatic monitoring of the periods spent by the sheep in the two areas. Forty-nine out of 50 sheep learnt to use the non-return gates when offered a concentrate feed reward during training. The method allowed error-free measurement of sheep movements between paddocks. A race could be added to the non-return gate to increase the level of work required to obtain access to another area. This would allow measurements of the motivation of sheep to obtain pasture resources and thus test the strength of diet preference at pasture.

This paper reviews recent work carried out by the Institute of Grassland and Environmental Research and collaborating organizations that addresses some of the impacts of grazing management on both species-rich and species-poor lowland neutral grassland. Results indicate that for species-rich grassland, lenient grazing pressure maintained botanical diversity and the abundance of positive indicator species of nature conservation value over a 5-year period and also enhanced faunal diversity and abundance reflecting improvements in spatial, architectural and temporal structure. However, there was no enhancement in positive indicator species and there was also an increase in pernicious weeds suggesting that grazing alone may not suffice to deliver all the biodiversity goals for these grasslands and that additional management interventions may be required. For species-poor grassland, results indicate that distinctive differences in structure can lead to differences in faunal diversity. There is also some tentative evidence that livestock breed may affect invertebrate species assemblages.

For a pharmacokinetic-pharmacodynamic study in opioid tolerant patients, who were treated with heroin in combination with methadone, a liquid chromatographic assay with tandem mass spectrometry detection (LC-MS/MS) was developed for the simultaneous determination of heroin, methadone, heroin metabolites 6-monoacetylmorphine, morphine, and morphine-6 and 3-glucuronide and methadone metabolite EMDP. To detect any abuse of substances besides the prescribed opioids the assay was extended with the detection of cocaine, its metabolites benzoylecgonine and norcocaine and illicit heroin adulterants acetylcodeine and codeine. Heroin-d6, morphine-d3, morphine-3-glucuronide-d3 and methadone-d9 were used as internal standards. The sample pre-treatment consisted of solid phase extraction using mixed mode sorbent columns (MCX Oasis). Chromatographic separation was performed at 25 degrees C on a reversed phase Zorbax column with a gradient mobile phase consisting of ammonium formate (pH 4.0) and acetonitrile. The run time was 15 min. MS with relatively mild electrospray ionisation under atmospheric pressure was applied. The triple quadrupole MS was operating in the positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 5-500 ng/mL for all analytes. The total recovery of heroin varied between 86 and 96% and of the heroin metabolites between 76 and 101%. Intra-assay and inter-assay accuracy and precision of all analytes were always within the designated limits (< or =20% at lower limit of quantification (LLQ) and < or =15% for other samples). This specific and sensitive assay was successfully applied in pharmacokinetic studies with medically prescribed heroin and toxicological cases.

In preparation for a treatment program concerning the medical coprescription of heroin and methadone to treatment-resistant addicts in the Netherlands, we studied a novel strategy for monitoring co-use of illicit (nonprescribed) heroin. A deuterated analogue of heroin was added (1:20) to pharmaceutical, smokable heroin (a powder mixture of 75% w/w diacetylmorphine base and 25% w/w caffeine anhydrate), to be used by inhalation after volatilization ("chasing the dragon"). Plasma and urine samples were collected from nine male patients who had used pharmaceutical, smokable heroin during a four-day stay in a closed clinical research unit, and these samples were analyzed by liquid chromatography coupled with tandem mass spectrometry. Ratios of deuterated and undeuterated diacetylmorphine and 6-acetylmorphine (MAM/MAM-d3) in plasma and urine were calculated from peak areas of these substances in the respective chromatograms. The MAM/MAM-d3 ratios in plasma and urine were normally distributed (with small standard deviations) and independent from concentrations of 6-acetylmorphine and from time after use of pharmaceutical heroin. A MAM/MAM-d3 ratio in urine above 32.8 was considered indicative of co-use of illicit heroin, and this value was associated with a false-positive rate of only 1% (95% confidence interval: -1 to 3%). The MAM/MAM-d3 ratio was detectable in urine for 4-9.5 h after use of pharmaceutical, smokable heroin. Addition of stable, isotopically labelled heroin to pharmaceutical, smokable heroin is considered to be a feasible strategy for the detection of co-use of illicit heroin by patients in heroin-assisted treatment.

In this paper we review the experimental development of agri-environment measures for use on grasslands. Sward structure has been shown to have a strong influence on birds' ability to forage in grasslands, but the effects of food abundance on foraging behaviour are poorly understood and this hinders development of grassland conservation measures. The experiments described have a dual purpose: to investigate the foraging ecology of birds on grasslands and to test candidate management measures. Most of the work featured focuses on increasing invertebrate food resources during the summer by increasing habitat heterogeneity. We also identify important gaps in the habitats provided by existing or experimental measures, where similar dual-purpose experiments are required.

Pairs of ewes or heifers were allowed to graze for short periods from previously prepared ‘homogeneous’ areas of ryegrass, in order to study their bite dimensions and movement patterns and to investigate the role of different species in initiating spatial heterogeneity. Apparent bite area was calculated from number of bites and total bitten area when ewes or heifers took 10–15 bites from an 80 cm ×80 cm area in a homogeneous Lolium perenne sward. Apparent bite depth was calculated from sward surface height (SSH) within and adjacent to bitten areas. Apparent bite mass was calculated from grazed stratum bulk density. Incisor arcade breadth was measured. Animals also grazed 20 m ×40 m plots for 45 min. Position and activity were recorded and distance travelled calculated. Number of bites and steps, number and duration of grazing bouts, feeding station dimensions and horizontal head sweep were recorded. Bites per bout, per feeding station and per m forward movement, bite rate, inter-bout interval, and distance travelled, speed of movement, number of steps, step length and step rate within and between bouts were calculated. Distribution of grazing bout and inter-bout durations and the animals’ foraging paths were tested for randomness. Apparent bite area for heifers was 2.2 times that for ewes and incisor arcade breadth 1.8 times that for ewes. Apparent bite depths were similar at 0.35 of SSH. SSH distribution within bitten areas was non-normal and differed between animal species. Heifers’ bite mass was 2.1 times that for ewes. Heifers had longer grazing bouts, more feeding stations per bout, moved farther per bout but had similar movement speed while grazing. Distance between feeding stations was similar between species but heifers’ feeding station residence time was twice as long. Heifers’ biting rate was lower but they took more bites per bout, per feeding station and per metre of forward movement. Mean head sweep distance was greater for heifers. Both species moved a similar distance between grazing bouts but ewes moved more slowly with more, shorter steps. For both species, grazing bout and inter-bout durations were not randomly distributed. At a 1 m 2 scale for both species and a 5 m 2 scale for heifers, movement was non-random with a strong propensity to walk in a straight line but at a 5 m 2 scale sheep movement was uniformly distributed on the circle.

Highly filled polypropylene (PP) composites have been produced by extrusion of polypropylenes with surface treated fillers. The aim is to include the highest proportion of filler that can provide hardness and high density, without undue brittleness. Modification of the filler surface provided significant enhancement of the processing properties that have been studied with parallel plate rheometry. The experimental results indicated that the viscoelastic behavior of melt flow of highly filled polypropylene composites significantly depended on the following properties of the fillers: aspect ratio, specific surface area and particle size in talc, calcium carbonate and barium sulfate filled polypropylene composites. Traditional surface modifiers such as stearic acid are useful, but titanates and in particular small amounts of silicones have provided the greatest rheological modification.

Three replicate paddocks, each of 0.235 ha, containing adjacent monocultures of perennial ryegrass or white clover [50:50 by ground area, 6 cm sward surface height (SSH) at start of experiment] were continuously stocked with three yearling and four mature non-lactating, non-pregnant Scottish halfbred ewes for 12 weeks. Herbage intake, grazing behaviour and dietary selection were measured on seven occasions. Clover SSH declined rapidly over the first 5 weeks then stabilized at 1.2-1.6 cm, whereas perennial ryegrass SSH rose slightly initially, then declined gradually. Animals initially included proportionately c . 0.6 white clover in their diet but, by the end of the experiment, this had fallen to 0.3. Total daily herbage intake declined over the 12 weeks from 1.8 kg dry matter (DM) day(-1) at the start to 1.0 kg DM day(-1) . Total grazing time increased from 561 min day(-1) to 649 min day(-1) at the end of the experiment. The results suggest that, despite overall herbage depletion and a greater depletion of white clover than perennial ryegrass as a result of the initial partial preference for white clover, the animals traded-off a reduced total intake and an increased grazing time in an attempt to maintain their initial preferred dietary composition.

Models to predict herbage intake were constructed using 168 dairy cow records from three grazing experiments. Variables included fell into three categories: animal state, sward state and animal behaviour. Linear regression models of varying complexity were obtained by removing variables from the best fitting model to reflect progressive lack of information availability on farms. Thus, behavioural variables were removed first, followed by sward surface height and milk fat concentration. Models were subject to outlier analysis and collinearity tests. Equivalent models were constructed using ridge regression to minimize collinearity problems. They were tested using 20 Holstein–Friesian dairy cows continuously stocked on a perennial ryegrass sward. A `best practice' treatment [7 cm sward surface height (SSH), 6 kg day−1 concentrate (C)] was used together with treatments of SSH5/C6, SSH7/C8, SSH7/C0 and SSH9/C6. The best model accounted for 0.37 of the variance in the estimation data and contained the following variables: concentrate intake, milk yield, milk fat concentration, days in milk, sward surface height and chewing rate while ruminating. Model performance against test data was generally poor. This was mainly because of consistent underprediction of herbage intake, caused in part by the higher average herbage intakes in the test data compared with the estimation data.

Highly filled polypropylene composites have been prepared with filler contents up to 43.8 vol.% (70 wt.%) after surface treatment of the fillers with titanate or silicone. The fillers used were calcium carbonate, talc and barium sulfate. Surface modification of the fillers facilitated extrusion and reduced brittleness while providing hard composites with high density. The high density and hardness provide a texture which is not characteristic of polypropylenes, but more like thermoset composites or ceramics; yet the composites can be extruded using typical thermoplastic processing equipment. The composition has been measured by thermogravimetry, and morphology observed with scanning electron microscopy. The tensile properties were measured and related to the composition, filler type and surface treatment.

Retirees who exhaust their savings while still alive are said to experience financial ruin. These savings are typically grown during the accumulation phase then spent during the retirement decumulation phase. Extensive research into invest-and-harvest decumulation strategies has been conducted, but recommendations differ markedly. This has likely been a source of concern and confusion for the retiree. Our goal is to find what has heretofore been elusive, namely an optimal decumulation strategy. Optimality implies that no alternate strategy exists or can be constructed that delivers a lower probability of ruin, given a fixed inflation-adjusted withdrawal rate., Proofs appendix with full C++ implementation is included

Meal patterns and rates of feed intake by grazing herbivores may be markedly different from those found in housed ruminants and monogastrics. Cumulative intakes over the evening meal (satiety curves) were measured using groups of sheep ( Ovis aries L.) grazing monocultures of white clover ( Trifolium repens L., cv. Kent Wild White) and ryegrass ( Lolium perenne L., cv. Parcour). Intake was measured by weighing ewes before and after grazing, with an allowance for insensible weight loss, for each of six groups in sequence; when grazing clover after 15, 30, 45, 60, 75 or >90 min and when grazing grass after 20, 40, 60, 80, 100 and >120 min. In each case, the sixth group was allowed to graze until a break of at least 6 min had occurred, which was taken to be an inter-meal as opposed to an intra-meal interval. Measurements were made on both herbage species using non-fasted control animals and animals that had been fasted for 24 h prior to measuring intake. Regressions of cumulative fresh and dry matter (DM) intakes against minutes of eating (excluding intra-meal intervals), constrained to pass through the origin, were best described by linear rather than curvilinear relationships. This showed that intake rates were constant within a meal. However, as the meal progressed, the number of intra-meal intervals increased and if these intervals were included in eating time, then the relationships were curvilinear with intake rate decreasing with time since the onset of the meal. The non-fasted animals had shorter meals than fasted animals and animals grazing clover had shorter meals than those grazing grass. The application of these results to intake control mechanisms is discussed.

Polypropylene (PP) composites with high filler content have been prepared with surface-treated fillers. The effect of the filler is twofold; nucleation of crystallization occurs, though the PP is also adsorbed onto the filler thereby retarding its motion. Differential scanning calorimetry has been used to study the crystallization of the PP. Melting and recrystallization during melting has been characterized by differential scanning calorimetry. The properties of the composites are more than an additive combination of the filler and polymer. In the case of highly filled composites, the morphology of the PP is important in limiting brittleness and for the strength of the interface between filler and polymer. Surface treatment of the filler has been found to have a significant control over the morphology and properties of the composites.

The pre-requisites for nutritional management of dairy cows are information about how much feed is being consumed as well as the nutrients that are being derived from that feed. Studies of feed intake and nutrient supply have been limited by difficult experimental techniques, particularly with grazing animals. The models derived from much earlier work are of only general applicability and there is a need for more site-specific information in order to benefit further from conceptual advances.We have adopted a different approach to studying herbage intake and nutrient supply, using less-invasive approaches as well as techniques that monitor more accessible aspects of these processes, such as jaw movements. These techniques have a major advantage, in addition to their value as research tools, because they could translate directly into commercial applications in on-farm monitoring. The use of diagnostics and behavioural recording is well explored in relation to health monitoring; here we argue for its potential to advance the application of knowledge about grazing and nutrition. We will illustrate this approach using our experiences in measuring grazing behaviour, using IGER behaviour recorders and assessing rumen function, using a series of non-invasive techniques.The IGER grazing behaviour recorder allows us to record jaw movements and hence grazing and ruminating time and bite dynamics. It also allows the recording of steps and is now being developed to incorporate non-invasive rumen state sensors. It has made a major contribution to our understanding of the foraging strategies of grazing animals and their effect on herbage intake. This technology has the potential to be developed for on-farm monitoring of foraging behaviour providing valuable inputs to the prediction of herbage intake, in decision support systems for grazing.The introduction of concept of protein degradation and microbial synthesis in the rumen are significant advances in protein rationing schemes. However, real progress has been limited because the lack of consistent experimental results means that models have little relevance to specific farm situations. We foresee considerable opportunities to monitor products of rumen degradation and synthesis that appear in milk (e.g. odd-chain fatty acids) or breath (e.g. sulphides).Taken together these technologies open the possibilities of an entirely new approach to nutritional management of dairy cows, with site-specific recommendations based on information gathered using new sensors that are incorporated into computerised feeding equipment and milking parlours.

Non-pregnant, non-lactating ewes grazed adjacent monocultures of white clover and perennial ryegrass with three sward surface height (SSH) combinations [6 cm white clover: 6 cm perennial ryegrass (c6g6), 3 cm white clover: 6 cm perennial ryegrass (c3g6), 3 cm white clover: 9 cm perennial ryegrass (c3g9)] at two stocking densities (21·3 or 29·8 ewes ha–1). Immediately prior to the experiment, all ewes grazed a c6g6 sward. Grazing time on each plant species was recorded during daylight over two 48 h-test periods. Subsequently, herbage intake rates for each species at each SSH were measured allowing intakes of each species to be calculated. For the first 24 h of both test periods (D1), ewes on treatment c3g6 spent less time grazing white clover than those on treatment c6g6 (228 vs. 362 min) and more time grazing perennial ryegrass (360 vs. 182 min). Total grazing time on treatment c3g6 was more than on treatment c6g6 (587 vs. 544 min) but the difference was not significant. Perennial ryegrass intake was higher (895 vs. 452 g), and white clover intake (814 vs. 1687 g), total intake (1719 vs. 2140 g) and proportion of white clover in the diet (0·460 vs. 0·794) were lower for treatment c3g6 than treatment c6g6. There were no significant differences in total grazing time, grazing time on either species, proportion of grazing time on white clover or proportion of white clover in the diet between treatment c3g6 and treatment c3g9. However, the higher intake rate of perennial ryegrass in treatment c3g9 led to higher perennial ryegrass and total intakes. For the second 24 h of both test periods (D2), ewes on treatment c3g6 again spent more time grazing perennial ryegrass than on treatment c6g6 (270 vs. 161 min) but time spent grazing white clover was similar (318 vs. 308 min). Total grazing time was significantly higher on treatment c3g6 than on treatment c6g6 (588 vs. 469 min) but proportion of grazing time on white clover was similar (0·554 vs. 0·668). Perennial ryegrass intake was significantly higher for treatment c3g6 than for treatment c6g6 (672 vs. 402 g) while white clover intake was significantly lower (1140 vs. 1435 g) but total intake was similar (1812 vs. 1836 g). The proportion of white clover in the diet was significantly lower for treatment c3g6 (0.628 vs. 0.785) than for treatment c6g6. The only significant differences between treatments c3g6 and c3g9 were in perennial ryegrass intake (672 vs. 906 g) and in total intake (1812 vs. 2287 g). Intake of perennial ryegrass on treatment c3g9 was also significantly greater than on treatment c6g6 (906 vs. 402 g) and total intake was higher (2287 vs. 1836 g). At the higher stocking density, time spent grazing perennial ryegrass and perennial ryegrass intake were significantly lower on D1 and D2 while total grazing time was also significantly lower and proportion of time grazing white clover and proportion of white clover in the diet were significantly higher at the higher stocking rate on D2. The results indicate that behaviour changed over the 48 h observation period for treatments c3g6 and c3g9 but behaviour remained relatively constant for animals on treatment c6g6. Ewes traded off dietary preference against total intake by altering grazing times on perennial ryegrass and white clover to achieve maximum net benefit.

The effect of physiological state lactating vs. non-lactating (dry) on grazing behaviour and herbage intake by Holstein-Friesian cows was examined on grass pastures maintained at 5, 7 or 9 cm sward surface height (SSH), typical of those provided under continuous variable stocking management. Intake rates were estimated over periods of 1 h by weighing the animals before and after grazing, retaining the faeces and urine excreted, and applying a correction for insensible weight loss. Grazing behaviour during these periods and over 24 h was recorded automatically using sensors to measure jaw movements. Bite mass (BM) did not differ significantly between lactating and dry cows but decreased ( P −1 as overall mean SSH decreased from 9 to 5 cm. An increase ( P =0.040) in grazing jaw movement (GJM) rate, from 75.3 to 80.3 GJM min −1 , as SSH decreased, did not compensate for reductions in bite mass, and intake rate declined linearly ( P =0.006) from 24.6 to 18.9 g OM min −1 . Lactating and dry cows compensated for the reduction in intake rate, by increasing total grazing time and total number of bites per day. As SSH decreased from 9 to 5 cm, lactating and dry cows increased total eating time (528 to 607 and 419 to 510 min), total GJM (40 400 to 49 300 and 31 300 to 40 600 GJM) and total bites (31 100 to 37 900 and 24 600 to 31 200 bites, respectively). As a result, there was no significant effect of SSH on daily intake of OM, although lactating cows had greater intakes than dry cows; 12.9 vs. 9.3 kg day −1 , ( P P P =0.060), allowing them 120 to 160 min more idling (i.e., non-grazing, non-ruminating) behaviour ( P =0.001).