The Growth and Direction of the Biodiesel Industry in the United States, 2007

The biodiesel industry in the United States has realized significant growth over the past decade through large increases in annual production and production capacity and a transition from smaller batch plants to larger-scale continuous producers. The larger, continuous-flow plants provide operating cost advantages over the smaller batch plants through their ability to capture co-products and reuse certain components in the production process. This paper uses a simple capital budgeting model developed by the authors along with production data supplied by industry sources to estimate production costs, return-on-investment levels, and break-even conditions for two common plant sizes (30 and 60 million gallon annual capacities) over a range of biodiesel and feedstock price levels. The analysis shows that the larger plant realizes returns to scale in both labor and capital costs, enabling the larger plant to pay up to $0.015 more per pound for the feedstock to achieve equivalent return levels as the smaller plant under the same conditions. The paper contributes to the growing literature on the biodiesel industry by using the most current conversion rates for the production technology and current price levels to estimate biodiesel production costs and potential plant performance, providing a useful follow-up to previous studies.

Supply chain management implementation in the Spanish grocery sector: An exploratory study

This paper explores the integration process that firms follow to implementSupply Chain Management (SCM) and the main barriers and benefits relatedto this strategy. This study has been inspired in the SCM literature,especially in the logistics integration model by Stevens [1]. Due to theexploratory nature of this paper and the need to obtain an in depthknowledge of the SCM development in the Spanish grocery sector, we used thecase study methodology. A multiple case study analysis based on interviewswith leading manufacturers and retailers was conducted.The results of this analysis suggest that firms seem to follow the integration process proposed by Stevens, integrating internally first, andthen, extending this integration to other supply chain members. The casesalso show that Spanish manufacturers, in general, seem to have a higherlevel of SCM development than Spanish retailers. Regarding the benefitsthat SCM can bring, most of the companies identify the general objectivesof cost and stock reductions and service improvements. However, withrespect to the barriers found in its implementation, retailers andmanufacturers are not coincident: manufacturers seem to see more barrierswith respect to aspects related to the other party, such as distrust and alack of culture of sharing information, while retailers find as mainbarriers the need of a know-how , the company culture and the historyand habits.

Relative price riddles in international business cycle theory: Are transport costs the explanation?

We study relative price behavior in an international business cyclemodel with specialization in production, in which a goods marketfriction is introduced through transport costs. The transporttechnology allows for flexible transport costs. We analyze whetherthis extension can account for the striking differences betweentheory and data as far as the moments of terms of trade and realexchange rates are concerned. We find that transport costs increaseboth the volatility of the terms of trade and the volatility of thereal exchange rate. However, unless the transport technology isspecified by a Leontief technology, transport costs do not resolvethe quantitative discrepancies between theory and data. Asurprising result is that transport costs may actually lower thepersistence of the real exchange rate, a finding that is in contrastto much of the emphasis of the empirical literature.

Review of the literature on reference pricing

This paper reviews the literature on reference pricing (RP) in pharmaceutical markets. The RP strategy for cost containment of expenditure on drugs is analyzed as part of the procurement mechanism. We review the existing literature and the state-of-the-art regarding RP by focusing on its economic effects. In particular, we consider: (1) the institutional context and problem-related factors which appear to underline the need to implement an RP strategy; i.e., its nature, characteristics and the sort of health care problems commonly addressed; (2) how RP operates in practice; that is, how third party-payers (the insurers/buyers) have established the RP systems existing on the international scene (i.e., information methods, monitoring procedures and legislative provisions); (3)the range of effects resulting from particular RP strategies (including effects on choice of appropriate pharmaceuticals, insurer savings, total drug expenditures, prices of referenced and non-referenced products and dynamic efficiency; (4) the market failures which an RP policy is supposed to address and the main advantages and drawbacks which emerge from an analysis of its effects. Results suggest that RP systems achieve better their postulated goals (1) if cost inflation in pharmaceuticals is due to high prices rather than to the excess of prescription rates, (2) when the larger is the existing difference in prices among equivalent drugs, and (3) more important is the actual market for generics.

DIGITAL LIBRARIES IN THE DEVELOPING COUNTRIES

Digital libraries (DL) are seen as a hope to developing countries in their struggle for accessing bibliographic resources, especially in a context where the traditional distribution mechanisms failed tragically. Several difficulties are however faced by these countries to build and use digital libraries, due mainly to its high development costs and to the poor existing ICT resources in these countries. This paper discusses the importance of digital libraries for developing countries and introduces the main challenges they face in building and using such libraries. The current alternatives and major initiatives for making digital information accessible to developing countries are also addressed.

Cardiac paraganglioma: diagnostic work up and review of the literature.

Paraganglioma of the heart are potentially invasive, highly vascularized tumors for which complete resection may be curative. Derived from the cardiac wall in most instances, resectability can be assessed after integration of the data provided by MRI in T2 sequence, and coronarography. A fully documented case of a large cardiac pheochromocytoma of the left atrium and AV groove is reported and the pertinent literature on the subject is here presented.

Appropriateness of use of infliximab in the Swiss IBD Cohort Study

Introduction: Anti-TNFs have significantly improved the management of Crohn's disease (CD), but not all patients will benefit from this therapy. We used data from the Swiss IBD Cohort Study (SIBDCS) and preset appropriateness criteria to examine the appropriateness of use of infliximab (IFX) in CD patients. aims & methods: EPACT II (European Panel on the Appropriateness of Crohn's disease Therapy) appropriateness criteria (www.epact.ch) have been developed by a formal panel process combining evidence from the published literature and expert opinion (end 2007), yielding 3 categories of indications: appropriate, uncertain, and inappropriate. Enrolment and follow-up of all SIBDCS patients were achieved with questionnaires relating to EPACT II criteria. Patients could correspond to several clinical categories; pregnant patients or those with stenosing disease could not be assessed using EPACT II criteria. A step-by-step analysis based on frequency allowed identification of the most appropriate indication for IFX in a given patient. results: 822 CD patients were included between November 2006 and March 2009. 146 patients (18%) were on IFX at inclusion (130 maintenance of remission, 16 new treatments). At inclusion, and in comparison with non-IFX treated patients, patients on infliximab were more frequently female (56% vs 51%), younger at diagnosis (27.4 years old vs 30.4) and had a slightly shorter disease duration (10.3 years vs 11.7). Disease extension was greater in these patients, who were mainly treated in university centres (83% vs 72%). IFX therapy was considered appropriate in 47%, uncertain in 36% and inappropriate in 18 % of patients (6% of situations could not be assessed). conclusion: In this cohort, most indications (47%) for IFX therapy were appropriate. Uncertain or inappropriate indications were mostly due to complex patient characteristics (e.g. complex fistulas, history of multiple drug-failures), which reflect the broad use of IFX in clinical practice. Cohort studies are well suited to evaluating the implementation of new scientific evidence in clinical practice.

Which anesthetic should be used in the treatment of refractory status epilepticus?

While the treatment of refractory status epilepticus (SE) relies on the use of anesthetic agents, mostly barbiturates, propofol, or midazolam, the study of the available literature discloses that the evidence level is low. Therapeutic coma induction appears straightforward for generalized convulsive or subtle SE, but this approach is debated for complex partial SE. Each anesthetic has its own advocates, and specific advantages and risks; furthermore, several different protocols have been reported regarding the duration and depth of sedation. However, it seems that the biological background of the patient (especially the etiology) remains the main prognostic determinant in SE. There is a clear need of controlled trials regarding this topic.

Transnational authority in the knowledge-based economy: Who sets the standards of ICT training and certification?

This article examines the extent and limits of nonstate forms of authority in international relations. It analyzes how the information and communication technology (ICT) infrastructure for the tradability of services in a global knowledge-based economy relies on informal regulatory practices for the adjustment of ICT-related skills. By focusing on the challenge that highly volatile and short-lived cycles of demands for this type of knowledge pose for ensuring the right qualification of the labor force, the article explores how companies and associations provide training and certification programs as part of a growing market for educational services setting their own standards. The existing literature on non-conventional forms of authority in the global political economy has emphasized that the consent of actors, subject to informal rules and some form of state support, remains crucial for the effectiveness of those new forms of power. However, analyses based on a limited sample of actors tend toward a narrow understanding of the issues concerned and fail to fully explore the differentiated space in which non state authority is emerging. This article develops a three-dimensional analytical framework that brings together the scope of the issues involved, the range of nonstate actors concerned, and the spatial scope of their authority. The empirical findings highlight the limits of these new forms of nonstate authority and shed light on the role of the state and international governmental organizations in this new context.

Alcohol consumption in late adolescence and early adulthood - where is the problem?

Risky single-occasion drinking (RSOD) is more common in late adolescence and early adulthood (approximately between the ages of 16 and 30) than in any other period in life. This is also the age when young people in Switzerland and many other European countries are legally allowed to buy and drink alcohol, but they usually do not yet have adult responsibilities. This paper reviews evidence from the international literature and provides examples of studies conducted in Switzerland demonstrating that (a) RSOD is by far most prevalent on Saturday evenings followed by Friday evenings, usually because young people go out and do not have any work or study responsibilities the next day; (b) RSOD results from drinking in private before going out ("predrinking") and accelerating the pace of drinking (i.e. increasing the number of drinks consumed per hour); (c) RSOD is often not accidental but purposeful,. to seek excitement, to have fun and to feel the effects of alcohol; (d) RSOD occurs predominantly outside the home, mostly in bars, pubs, discos or at special events and festivals; (e) RSOD often results in intended and unintended injuries and other acute consequences, which are leading risk factors for mortality and morbidity in this age group. Effective prevention strategies should include attempts to reduce opportunities to engage in heavy drinking as well as strategies to reduce its harmful consequences.

New insights on the crystalline forms in binary systems of n-alkanes: Characterization of the solid ordered phases in the phase diagram tricosane + pentacosane

X-ray diffraction analyses of the pure components n-tricosane and n-pentacosane and of their binary mixed samples have enabled us to characterize the crystalline phases observed at low temperature. On the contrary to what was announced in literature on the structural behavior of mixed samples in odd-odd binary systems with D n = 2, the three domains are not all orthorhombic. This work has enabled us to show that two of the domains are, in fact, monoclinic, (Aa, Z = 4) and the other one is orthorhombic (Pca21, Z = 4). The conclusions drawn in this work can be easily transposed to other binary systems of n-alkanes.

Quoi de neuf dans le traitement des séminomes [What's new in the treatment of seminomas?]

Pure testicular seminoma is a rare disease with an excellent prognosis. Its management is controversial. In stage I disease, several treatment options are considered. Those are radiation therapy alone, chemotherapy alone or active surveillance, which is becoming increasingly popular. For more advanced stages, treatment is based on chemotherapy with or without radiation therapy. In this article, we review thoroughly the existing literature and recent recommendations the various treatment options, their advantages and disadvantages in different stages of the disease.

Geochemical changes at the Permian-Triassic transition in Southern Alps and adjacent area: a review

Compilation of the recent literature from the Southern Alps and adjacent area confirms the geochemical variations of unusual amplitudes during the Permian-Triassic boundary interval (PTBI). A great attention has been given to the negative δ13C anomaly within the Tesero Member close to the Permian-Triassic boundary. Very detailed geochemical works have been done on the scientific Gartnerkofel core (Gk-1) and on the Slovenian sections. Major minor and rare earth elements (REE) data are reported and show a marked enrichment in alkaline metals and REE of some levels of the boundary interval. But recent studies show that the low Iridium anomalies and the Osmium and Helium isotopes anomalies lack the characteristics of a large extraterrestrial impact.

Analyse des taux de renvoi entre médecins praticiens: une revue de la littérature. [Analysis of referral rate between medical practitioners: a review of the literature].

The authors are discussing the results of the international literature with regards to referrals between ambulatory physicians. There are still few studies on this problem and the methodologies used are often too different to make valid comparisons. However, the earned results suggest more questions than they give answers to the determinants of the referral process. This can be explained by the multidimensionality of factors which are involved in the decision to refer a patient to another practitioner, particularly by the complex interaction between the characteristics of each patient, practitioner and the sanitary system itself.

Cheminformatic studies of molecular properties and their influence on bioactivity in the context of drug discovery

Molecular shape has long been known to be an important property for the process of molecular recognition. Previous studies postulated the existence of a drug-like shape space that could be used to artificially bias the composition of screening libraries, with the aim to increase the chance of success in Hit Identification. In this work, it was analysed to which extend this assumption holds true. Normalized Principal Moments of Inertia Ratios (NPRs) have been used to describe the molecular shape of small molecules. It was investigated, whether active molecules of diverse targets are located in preferred subspaces of the NPR shape space. Results illustrated a significantly stronger clustering than could be expected by chance, with parts of the space unlikely to be occupied by active compounds. Furthermore, a strong enrichment of elongated, rather flat shapes could be observed, while globular compounds were highly underrepresented. This was confirmed for a wide range of small molecule datasets from different origins. Active compounds exhibited a high overlap in their shape distributions across different targets, making a purely shape­ based discrimination very difficult. An additional perspective was provided by comparing the shapes of protein binding pockets with those of their respective ligands. Although more globular than their ligands, it was observed that binding sites shapes exhibited a similarly skewed distribution in shape space: spherical shapes were highly underrepresented. This was different for unoccupied binding pockets of smaller size. These were on the contrary identified to possess a more globular shape. The relation between shape complementarity and exhibited bioactivity was analysed; a moderate correlation between bioactivity and parameters including pocket coverage, distance in shape space, and others could be identified, which reflects the importance of shape complementarity. However, this also suggests that other aspects are of relevance for molecular recognition. A subsequent analysis assessed if and how shape and volume information retrieved from pocket or respective reference ligands could be used as a pre-filter in a virtual screening approach. ln Lead Optimization compounds need to get optimized with respect to a variety of pararneters. Here, the availability of past success stories is very valuable, as they can guide medicinal chemists during their analogue synthesis plans. However, although of tremendous interest for the public domain, so far only large corporations had the ability to mine historical knowledge in their proprietary databases. With the aim to provide such information, the SwissBioisostere database was developed and released during this thesis. This database contains information on 21,293,355 performed substructural exchanges, corresponding to 5,586,462 unique replacements that have been measured in 35,039 assays against 1,948 molecular targets representing 30 target classes, and on their impact on bioactivity . A user-friendly interface was developed that provides facile access to these data and is accessible at http//www.swissbioisostere.ch. The ChEMBL database was used as primary data source of bioactivity information. Matched molecular pairs have been identified in the extracted and cleaned data. Success-based scores were developed and integrated into the database to allow re-ranking of proposed replacements by their past outcomes. It was analysed to which degree these scores correlate with chemical similarity of the underlying fragments. An unexpectedly weak relationship was detected and further investigated. Use cases of this database were envisioned, and functionalities implemented accordingly: replacement outcomes are aggregatable at the assay level, and it was shawn that an aggregation at the target or target class level could also be performed, but should be accompanied by a careful case-by-case assessment. It was furthermore observed that replacement success depends on the activity of the starting compound A within a matched molecular pair A-B. With increasing potency the probability to lose bioactivity through any substructural exchange was significantly higher than in low affine binders. A potential existence of a publication bias could be refuted. Furthermore, often performed medicinal chemistry strategies for structure-activity-relationship exploration were analysed using the acquired data. Finally, data originating from pharmaceutical companies were compared with those reported in the literature. It could be seen that industrial medicinal chemistry can access replacement information not available in the public domain. In contrast, a large amount of often-performed replacements within companies could also be identified in literature data. Preferences for particular replacements differed between these two sources. The value of combining different endpoints in an evaluation of molecular replacements was investigated. The performed studies highlighted furthermore that there seem to exist no universal substructural replacement that always retains bioactivity irrespective of the biological environment. A generalization of bioisosteric replacements seems therefore not possible. - La forme tridimensionnelle des molécules a depuis longtemps été reconnue comme une propriété importante pour le processus de reconnaissance moléculaire. Des études antérieures ont postulé que les médicaments occupent préférentiellement un sous-ensemble de l'espace des formes des molécules. Ce sous-ensemble pourrait être utilisé pour biaiser la composition de chimiothèques à cribler, dans le but d'augmenter les chances d'identifier des Hits. L'analyse et la validation de cette assertion fait l'objet de cette première partie. Les Ratios de Moments Principaux d'Inertie Normalisés (RPN) ont été utilisés pour décrire la forme tridimensionnelle de petites molécules de type médicament. Il a été étudié si les molécules actives sur des cibles différentes se co-localisaient dans des sous-espaces privilégiés de l'espace des formes. Les résultats montrent des regroupements de molécules incompatibles avec une répartition aléatoire, avec certaines parties de l'espace peu susceptibles d'être occupées par des composés actifs. Par ailleurs, un fort enrichissement en formes allongées et plutôt plates a pu être observé, tandis que les composés globulaires étaient fortement sous-représentés. Cela a été confirmé pour un large ensemble de compilations de molécules d'origines différentes. Les distributions de forme des molécules actives sur des cibles différentes se recoupent largement, rendant une discrimination fondée uniquement sur la forme très difficile. Une perspective supplémentaire a été ajoutée par la comparaison des formes des ligands avec celles de leurs sites de liaison (poches) dans leurs protéines respectives. Bien que plus globulaires que leurs ligands, il a été observé que les formes des poches présentent une distribution dans l'espace des formes avec le même type d'asymétrie que celle observée pour les ligands: les formes sphériques sont fortement sous­ représentées. Un résultat différent a été obtenu pour les poches de plus petite taille et cristallisées sans ligand: elles possédaient une forme plus globulaire. La relation entre complémentarité de forme et bioactivité a été également analysée; une corrélation modérée entre bioactivité et des paramètres tels que remplissage de poche, distance dans l'espace des formes, ainsi que d'autres, a pu être identifiée. Ceci reflète l'importance de la complémentarité des formes, mais aussi l'implication d'autres facteurs. Une analyse ultérieure a évalué si et comment la forme et le volume d'une poche ou de ses ligands de référence pouvaient être utilisés comme un pré-filtre dans une approche de criblage virtuel. Durant l'optimisation d'un Lead, de nombreux paramètres doivent être optimisés simultanément. Dans ce contexte, la disponibilité d'exemples d'optimisations réussies est précieuse, car ils peuvent orienter les chimistes médicinaux dans leurs plans de synthèse par analogie. Cependant, bien que d'un extrême intérêt pour les chercheurs dans le domaine public, seules les grandes sociétés pharmaceutiques avaient jusqu'à présent la capacité d'exploiter de telles connaissances au sein de leurs bases de données internes. Dans le but de remédier à cette limitation, la base de données SwissBioisostere a été élaborée et publiée dans le domaine public au cours de cette thèse. Cette base de données contient des informations sur 21 293 355 échanges sous-structuraux observés, correspondant à 5 586 462 remplacements uniques mesurés dans 35 039 tests contre 1948 cibles représentant 30 familles, ainsi que sur leur impact sur la bioactivité. Une interface a été développée pour permettre un accès facile à ces données, accessible à http:/ /www.swissbioisostere.ch. La base de données ChEMBL a été utilisée comme source de données de bioactivité. Une version modifiée de l'algorithme de Hussain et Rea a été implémentée pour identifier les Matched Molecular Pairs (MMP) dans les données préparées au préalable. Des scores de succès ont été développés et intégrés dans la base de données pour permettre un reclassement des remplacements proposés selon leurs résultats précédemment observés. La corrélation entre ces scores et la similarité chimique des fragments correspondants a été étudiée. Une corrélation plus faible qu'attendue a été détectée et analysée. Différents cas d'utilisation de cette base de données ont été envisagés, et les fonctionnalités correspondantes implémentées: l'agrégation des résultats de remplacement est effectuée au niveau de chaque test, et il a été montré qu'elle pourrait également être effectuée au niveau de la cible ou de la classe de cible, sous réserve d'une analyse au cas par cas. Il a en outre été constaté que le succès d'un remplacement dépend de l'activité du composé A au sein d'une paire A-B. Il a été montré que la probabilité de perdre la bioactivité à la suite d'un remplacement moléculaire quelconque est plus importante au sein des molécules les plus actives que chez les molécules de plus faible activité. L'existence potentielle d'un biais lié au processus de publication par articles a pu être réfutée. En outre, les stratégies fréquentes de chimie médicinale pour l'exploration des relations structure-activité ont été analysées à l'aide des données acquises. Enfin, les données provenant des compagnies pharmaceutiques ont été comparées à celles reportées dans la littérature. Il a pu être constaté que les chimistes médicinaux dans l'industrie peuvent accéder à des remplacements qui ne sont pas disponibles dans le domaine public. Par contre, un grand nombre de remplacements fréquemment observés dans les données de l'industrie ont également pu être identifiés dans les données de la littérature. Les préférences pour certains remplacements particuliers diffèrent entre ces deux sources. L'intérêt d'évaluer les remplacements moléculaires simultanément selon plusieurs paramètres (bioactivité et stabilité métabolique par ex.) a aussi été étudié. Les études réalisées ont souligné qu'il semble n'exister aucun remplacement sous-structural universel qui conserve toujours la bioactivité quel que soit le contexte biologique. Une généralisation des remplacements bioisostériques ne semble donc pas possible.