Pleiotropy and the low cost of individual traits promote cooperation.

The evolution of cooperation is thought to be promoted by pleiotropy, whereby cooperative traits are coregulated with traits that are important for personal fitness. However, this hypothesis faces a key challenge: what happens if mutation targets a cooperative trait specifically rather than the pleiotropic regulator? Here, we explore this question with the bacterium Pseudomonas aeruginosa, which cooperatively digests complex proteins using elastase. We empirically measure and theoretically model the fate of two mutants-one missing the whole regulatory circuit behind elastase production and the other with only the elastase gene mutated-relative to the wild-type (WT). We first show that, when elastase is needed, neither of the mutants can grow if the WT is absent. And, consistent with previous findings, we show that regulatory gene mutants can grow faster than the WT when there are no pleiotropic costs. However, we find that mutants only lacking elastase production do not outcompete the WT, because the individual cooperative trait has a low cost. We argue that the intrinsic architecture of molecular networks makes pleiotropy an effective way to stabilize cooperative evolution. Although individual cooperative traits experience loss-of-function mutations, these mutations may result in weak benefits, and need not undermine the protection from pleiotropy.

Conflicting claims problem associated with cost sharing of a network

A minimum cost spanning tree (mcst) problem analyzes the way to efficiently connect individuals to a source when they are located at different places. Once the efficient tree is obtained, the question on how allocating the total cost among the involved agents defines, in a natural way, a confliicting claims situation. For instance, we may consider the endowment as the total cost of the network, whereas for each individual her claim is the maximum amount she will be allocated, that is, her connection cost to the source. Obviously, we have a confliicting claims problem, so we can apply claims rules in order to obtain an allocation of the total cost. Nevertheless, the allocation obtained by using claims rules might not satisfy some appealing properties (in particular, it does not belong to the core of the associated cooperative game). We will define other natural claims problems that appear if we analyze the maximum and minimum amount that an individual should pay in order to support the minimum cost tree. Keywords: Minimum cost spanning tree problem, Claims problem, Core JEL classification: C71, D63, D71.

Cost-effectiveness of Tenofovir / Emtricitabine / Efavirenz versus Zidovudine / Lamivudine / Efavirenz as fist-line regimens for the treatment of HIV-infected patients in low-income settings

The Highly Active Antiretroviral Therapy (HAART) is the combination of at least three antiretroviral compounds. The combination purpose is to reduce the likelihood of drug resistance. However in the long-term the resistance to the first-line combination occurs and leads to treatment failure. Thus, a second-line and even a third-line regimen are recommended in the long run. [...] [P. 5] The two treatment alternatives under comparison: Tenofovir (300 mg) CO-formulated with Emtricitabine (200 mg) and Efavirenz (600 mg) currently known under the brand name Atripla (R) was introduced in July 2006 in the United States market. The excellent safety profile and ease of use make this combination a perfect first-line regimen in low-income settings. Therefore, this treatment option was recommended in WHO 2006 reviewed guidelines. Unfortunately, Tenofovir and Emtricitabine compounds are still costly and not yet widely available. For a matter of simplification this regimen is referred in this report as "the recent" therapy. Initially, we had in mind to consider the most frequently used first-line regimen in low-income countries (Stavudine / Larnivudme / Nevirapine) as a comparator for this economic evaluation. Unfortunately, according to the literature review results (see Annex 3); there was no data available comparing head to head the effectiveness of this regimen with the recent one. Instead, we selected a less frequently but commonly used first-line regimen in low-income countries as a comparator: Zidovudine, Lamivudine, Efavirenz. This combination has extensive experience in durability, safety and toxicity and seems to be an optimal choice for a first-line regimen according to the clinical trial group 384 team. Furthermore, Zidovudine, one of the compounds of this combination is now recommended as one of the preferred NNRTI [Non Nucleoside Reverse Transcriptase Inhibitors] options to be considered by countries instead of Stavudine (the most used NNRTI in limited-income countries). As this combination has been included in the WHO guidelines as a first-line therapy since 2003 when WHO launched the "3 by 5" scaling-up initiative, this combination of drugs is referred in this report as the "old" therapy. Objectives: The primary objective of this economic evaluation is to compare the two first-line HAARTs introduced above, in a low-income setting context. Both of these combinations are recommended by the 2006 WHO guidelines as potential first-line regimens. The secondary objective is to provide a simplified and comprehensible cost-effectiveness modeling tool in order to help policy makers, in resource-limited settings, make decisions about which first-line HAART to fund using the scarce resources available. [P. 6-7]

Current and future trens in the quality control of pharmaceuticals and biopharmaticals : impacts on Cost of Goods Sold (COGS)

[Summary] 2. Roles of quality control in the pharmaceutical and biopharmaceutical industries. - 2.1. Pharmaceutical industry. - 2.2. Biopharmaceutical industry. - 2.3. Policy and regulatory. - 2.3.1. The US Food and Drug Administration (FDA). - 2.3.2. The European Medicine Agency (EMEA). - 2.3.3. The Japanese Ministry of Work, Labor and Welfare (MHLW). - 2.3.4. The Swiss Agency for Therapeutic Products (Swissmedic). - 2.3.5. The International Conference on Harmonization (ICH). - - 3. Types of testing. - 3.1. Microbiological purity tests. - 3.2. Physiochemical tests. - 3.3. Critical to quality steps. - 3.3.1. API starting materials and excipients. - 3.3.2. Intermediates. - 3.3.3. APIs (drug substances) and final drug product. - 3.3.4. Primary and secondary packaging materials fro drug products. - - 4. Manufacturing cost and quality control. - 4.1.1. Pharmaceutical manufacturing cost breakdown. - 4.1.2. Biopharmaceutical manufacturing cost breakdown. - 4.2. Batch failure / rejection / rework / recalls. - - 5. Future trends in the quality control of pharmaceuticals and biopharmaceuticals. - 5.1. Rapid and real time testing. - 5.1.1. Physio-chemicals testing. - 5.1.2. Rapid microbiology methods

Solitary pulmonary nodule and 18F-FDG PET/CT. Part 2: accuracy, cost-effectiveness, and current recommendations

Abstract A solitary pulmonary nodule is a common, often incidental, radiographic finding. The investigation and differential diagnosis of solitary pulmonary nodules remain complex, because there are overlaps between the characteristics of benign and malignant processes. There are currently many strategies for evaluating solitary pulmonary nodules. The main objective is to identify benign lesions, in order to avoid exposing patients to the risks of invasive methods, and to detect cases of lung cancer accurately, in order to avoid delaying potentially curative treatment. The focus of this study was to review the evaluation of solitary pulmonary nodules, to discuss the current role of 18F-fluorodeoxyglucose positron-emission tomography, addressing its accuracy and cost-effectiveness, and to detail the current recommendations for the examination in this scenario.

Warranty Practices and Costs in the Industry of Welding Machines Manufacturing

The objective of the master’s thesis is to define the warranty practices and costs in the welding machines manufacturing company and do a proposal for a warranty policy based on the practices and costs. The study include a disquisition of the warranty practices in the subsidiaries and distributor sales. The disquisition of the warranty practices introduces the information relates to warranty period, warranty costs, including repair, spare part and other costs, the practices with the replaced parts, the utilization rate of the eWarranty system and information relates to special arrangements in the warranties. The warranty costs are defined besides the group level also separately per regions and product families. From some product families the disquisition is done per products. In this study is also done a proposal for a warranty policy for the company. The proposal speaks out the length of warranty period, the compensation of the warranty costs, the practices with replaced parts and usage of eWarranty system.

Parental body condition does not correlate with offspring sex-ratio in Cory's shearwater

We analyzed offspring sex ratio variation in Mediterranean Cory's Shearwater (Calonectris d. diomedea) during two consecutive breeding seasons in two colonies. We test for differential breeding conditions between years and colonies looking at several breeding parameters and parental condition. We then explored the relationship between offspring sex ratio and parental condition and breeding parameters. This species is sexually dimorphic with males larger and heavier than females; consequently we expected differential parental cost in rearing sexes, or a greater sensitivity of male chicks to adverse conditions, which may lead to biased sex ratios. Chicks were sexed molecularly by the amplification of the CHD genes. Offspring sex ratio did not differ from parity, either at hatching or fledging, regardless of the colony or year. However, parental body condition and breeding parameters such as egg size and breeding success were different between years and colonies. Nevertheless, neither nestling mortality nor body condition at fledging varied between years or colonies, suggesting that male and female chicks were probably not differentially affected by variability in breeding conditions.

Climate Change and the Cost of Carbon Sequestration: The Case of Forest Management

The Kyoto protocol allows Annex I countries to deduct carbon sequestered by land use, land-use change and forestry from their national carbon emissions. Thornley and Cannell (2000) demonstrated that the objectives of maximizing timber and carbon sequestration are not complementary. Based on this finding, this paper determines the optimal selective management regime taking into account the underlying biophysical and economic processes. The results show that the net benefits of carbon storage only compensate the decrease in net benefits of timber production once the carbon price has exceeded a certain threshold value. The sequestration costs are significantly lower than previous estimates

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia, Spain

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Fair value versus historic cost-valuation for biological assets: Implications for the quality of financial information

[spa] Este trabajo realiza un estudio empírico sobre los efectos, que se señalan en las discusiones teóricas, de la utilización del valor razonable (VR) frente al coste histórico (CH), utilizando dos muestras de explotaciones agrícolas, una de las cuales valora sus activos biológicos a CH y la otra a VR. No se encontraron diferencias significativas en los beneficios e ingresos entre ambas muestras, ni siquiera en sus volatilidades. Tampoco se encontraron diferencias significativas en rentabilidad, manipulación contable, ni en el poder de ambos criterios de valoración para predecir los flujos de tesorería. Por el contrario, la mayor parte de los tests realizados revelan un mayor poder de los beneficios calculados bajo el VR para la predicción de los beneficios futuros, respecto de cuando son calculados bajo el CH. El estudio proporciona también evidencia empírica de prácticas contables defectuosas de CH en el sector agrícola, concluyendo que el VR puede representar un criterio de valoración interesante para un sector, como el agrícola, caracterizado por el predominio de pequeñas explotaciones familiares.

Fair value versus historic cost-valuation for biological assets: Implications for the quality of financial information

[spa] Este trabajo realiza un estudio empírico sobre los efectos, que se señalan en las discusiones teóricas, de la utilización del valor razonable (VR) frente al coste histórico (CH), utilizando dos muestras de explotaciones agrícolas, una de las cuales valora sus activos biológicos a CH y la otra a VR. No se encontraron diferencias significativas en los beneficios e ingresos entre ambas muestras, ni siquiera en sus volatilidades. Tampoco se encontraron diferencias significativas en rentabilidad, manipulación contable, ni en el poder de ambos criterios de valoración para predecir los flujos de tesorería. Por el contrario, la mayor parte de los tests realizados revelan un mayor poder de los beneficios calculados bajo el VR para la predicción de los beneficios futuros, respecto de cuando son calculados bajo el CH. El estudio proporciona también evidencia empírica de prácticas contables defectuosas de CH en el sector agrícola, concluyendo que el VR puede representar un criterio de valoración interesante para un sector, como el agrícola, caracterizado por el predominio de pequeñas explotaciones familiares.

Fair value versus historical cost-based valuation for biological assets: Predictability of financial information

There is an intense debate on the convenience of moving from historical cost (HC) toward the fair value (FV) principle. The debate and academic research is usually concerned with financial instruments, but the IAS 41 requirement of fair valuation for biological assets brings it into the agricultural domain. This paper performs an empirical study with a sample of Spanish farms valuing biological assets at HC and a sample applying FV, finding no significant differences between both valuation methods to assess future cash flows. However, most tests reveal more predictive power of future earnings under fair valuation of biological assets, which is not explained by differences in volatility of earnings and profitability. The study also evidences the existence of flawed HC accounting practices for biological assets in agriculture, which suggests scarce information content of this valuation method in the predominant small business units existing in the agricultural sector in advanced Western countries

Fenestra Oy:n tuotekustannuslaskennan kehittäminen – Case oviteollisuus

Kilpailluilla markkinoilla menestyäkseen yrityksen tulee tuntea oman tuotannon kustannusrakenne. Yrityksen täytyy menestyäkseen tarjota asiakkaalle yksilöllisiä tuotteita kilpailukykyiseen hintaan. Tämä aiheuttaa haasteita tuotannolle, mutta myös tuotekustannuslaskennalle; perinteisin tuotekustannuslaskentamenetelmin ei enää pystytä huomioimaan laajan tuotevalikoiman tuotteiden valmistuksen eroavaisuuksia. Tämän diplomityön tarkoituksena on selvittää Fenestra Oy:n tuotekustannuslaskentakäytäntöjen soveltuvuus nykyhetkeen. Vertailukohdaksi työssä määritellään vaihtoehtoinen laskentamalli tuotekustannusten laskemiseksi. Uuden laskentamallin soveltuvuutta käytäntöön tutkitaan esimerkkilaskelmin, joiden tuloksia verrataan Fenestra Oy:n nykyisen laskennan tuloksiin. Laskentamallilla aikaansaadut tulokset poikkeavat Fenestra Oy:n nykyisestä laskennasta ennakoidulla tavalla; perinteisin menetelmin valmistukseltaan yksinkertaisille tuotteille kohdistuu liikaa kustannuksia ja monimutkaisille liian vähän. Laadittu laskentamalli on diplomityön laajuuden puitteessa varsin yksinkertainen, mutta suuntaa-antava. Jatkokehityskohteena laskennan kehittämiseksi tuotannosta tulisi alkaa kerätä tarkemmin tietoa ja materiaalikäytön osalta tarkkaa hukkaselvitystä.

The Present State and a Development Plan of Cost Accounting in Batch Production of Wind Turbine Gears

The aim of this master’s thesis was to document the present state and to create a development plan for Moventas Wind’s cost accounting. The current cost accounting system was evaluated and most fundamental problems were chosen as areas of focus in development work. The development plan includes both short- and long-term development proposals for problems identified. This report presents two alternative models for product costing. Benchmarking of cost accounting practices and modern cost accounting theories were used in development of cost accounting. It was found that the current cost accounting system functions quite well and the adjustments in unit cost rate calculation have only a minor influence on costs of goods sold. An OEE-based standard cycle concept was also developed and it was found that the implementation of this new system is worthwhile in the long-term.