Timing of Capacity Change: Models for Capital Intensive Industry

The suitable timing of capacity investments is a remarkable issue especially in capital intensive industries. Despite its importance, fairly few studies have been published on the topic. In the present study models for the timing of capacity change in capital intensive industry are developed. The study considers mainly the optimal timing of single capacity changes. The review of earlier research describes connections between cost, capacity and timing literature, and empirical examples are used to describe the starting point of the study and to test the developed models. The study includes four models, which describe the timing question from different perspectives. The first model, which minimizes unit costs, has been built for capacity expansion and replacement situations. It is shown that the optimal timing of an investment can be presented with the capacity and cost advantage ratios. After the unit cost minimization model the view is extended to the direction of profit maximization. The second model states that early investments are preferable if the change of fixed costs is small compared to the change of the contribution margin. The third model is a numerical discounted cash flow model, which emphasizes the roles of start-up time, capacity utilization rate and value of waiting as drivers of the profitable timing of a project. The last model expands the view from project level to company level and connects the flexibility of assets and cost structures to the timing problem. The main results of the research are the solutions of the models and analysis or simulations done with the models. The relevance and applicability of the results are verified by evaluating the logic of the models and by numerical cases.

Using tools to help cost estimating and pricing: examination of costing model's and cost breakdown's workability and their capability to cooperative work

Tämä diplomityö käsittelee työkaluja, jotka on suunniteltu kustannusten ennakointiin ja hinnan asetantaan. Aluksi on käyty läpi perinteisen ja toimintoperusteisen kustannuslaskennan perusteita. Näiden menetelmien välisiä eroja on tarkasteltu ja toimintoperusteisen kustannuslaskennan paremmin sopivuus nykypäivän yrityksille on perusteltu. Toisena käsitellään hinnoittelu. Hinnan merkitys, hinnoittelumenetelmät ja päätös lopullisesta hinnasta on käyty läpi. Hinnoittelun jälkeen esitellään kustannusjärjestelmät ja kustannusten arviointi. Nämä asiat todistavat, että tarkat kustannusarviot ovat elintärkeitä yritykselle. Tuotteen kustannusarviointi, hinnan asetanta ja tarjoaminen ovat erittäin merkityksellisiä asioita ottaen huomioon koko projektin elinkaaren ja tulevat tuotot. Nykyään on yleistä käyttää työkaluja kustannusarvioinnissa ja joskus myös hinnoittelussa. Työkalujen luotettavuus on tiedettävä, ennenkuin työkalut otetaan käyttöön. Myös työkalujen käyttäjät täytyy perehdyttää hyvin. Muuten yritys todennäköisesti kohtaa odottamattomia ja epämiellyttäviä yllätyksiä.

Fish oil replacement by soybean oil in the diet of fat snook juveniles

The objective of this work was to evaluate fish oil replacement by soybean oil in diets, as for the effects on the performance and body composition of juveniles of fat snook (Centropomus parallelus). The experiment was carried out in a randomized block design, with three treatments (lipid sources) and six replicates, in a 60-day period. Fat snook juveniles (24.17±0.28g) were distributed in 18 experimental tanks of 200 L each, equipped with aeration and heating systems, under continuous water renovation (800% per day). Three isoproteic (44% CP) and isoenergetic (4,635 kcal CE kg-1) diets were formulated to comprise three replacement rates (0, 50, and 100%) of fish oil by soybean oil. Biometric analyses were done to evaluate fish performance, and two entire specimens from each replicate were used for body composition analyses. The zootechnical indices of weight gain (38.68±5.41 g), feed conversion (1.38±0.10), and specific growth at 1.70±0.18% weight gain per day were considered satisfactory. Lipid source substitution does not affect the performance and body composition of fat snook juveniles, which suggests that soybean oil can replace fish oil in diet formulation.

Cross-sectional analysis of testosterone therapies in hypopituitary men on stable pituitary hormone replacement.

OBJECTIVE: The last decade has seen a proliferation in options for testosterone replacement. However, little is known as to the benefits of different treatment modalities. Our objective was to determine the testosterone prescription pattern and to examine the impact on various outcome measures. SUBJECTS AND METHODS: A total of 816 adult-onset hypopituitary males on stable pituitary replacement for at least 1 year were identified from the KIMS database. Patients were classified as either eugonadal (n = 106), or hypogonadal (n = 710) on intramuscular (IM, n = 558), oral (n = 74), transdermal (n = 61), and depot (n = 17) testosterone. RESULTS: After 1 year of stable pituitary replacement therapy, body composition, cardiovascular parameters, GH replacement and quality of life were not significantly different in androgen-replaced hypogonadal patients compared to eugonadal patients. There were no differences in outcome variables within the hypogonadal group according to the testosterone replacement regimen used and no difference in response to GH therapy. CONCLUSIONS: The majority of hypopituitary patients in the last decade have received IM testosterone. Body composition, cardiovascular parameters, GH replacement and quality of life were not different between eugonadal and hypogonadal patients and were not differentially affected by the mode of testosterone replacement. These findings are reassuring that there is no major difference in response to different testosterone replacement regimens.

Inter-limb coordination and energy cost in swimming.

OBJECTIVES: This study investigated the relationship between inter-arm coordination and the energy cost of locomotion in front crawl and breaststroke and explored swimmers' flexibility in adapting their motor organization away from their preferred movement pattern. DESIGN: Nine front-crawlers performed three 300-m in front crawl and 8 breaststrokers performed three 200-m in breaststroke at constant submaximal intensity and with 5-min rests. Each trial was performed randomly in a different coordination pattern: freely chosen, 'maximal glide' and 'minimal glide'. Two underwater cameras videotaped frontal and side views to analyze speed, stroke rate, stroke length and inter-limb coordination. METHODS: In front crawl, inter-arm coordination was quantified by the index of coordination (IdC) and the leg beat kicks were counted. In breaststroke, four time gaps quantified the arm to leg coordination (i.e., time between leg and arm propulsions; time between beginning, 90° flexion and end of arm and leg recoveries). The energy cost of locomotion was calculated from gas exchanges and blood lactate concentration. RESULTS: In both front crawl and breaststroke, the freely chosen coordination corresponded to glide pattern and showed the lowest energy cost (12.8 and 17.1Jkg(-1)m(-1), respectively). Both front-crawlers and breaststrokers were able to reach 'maximal glide' condition (respectively, +35% and +28%) but not 'minimal glide' condition for front crawl. CONCLUSIONS: The freely chosen pattern appeared more economic because more trained. When coordination was constrained, the swimmers had higher coordination flexibility in breaststroke than in front crawl, suggesting that breaststroke coordination was easier to regulate by changing glide time.

Oxygen adsorption on Cu(211) and structurally and chemically modified Cu(100)

Kuparipinnan hapettuminen on viimevuosina ollut suosittu tutkimuskohde materiaalitieteissä kuparin laajan teollisuuskäytön vuoksi. Teollisuussovellusten, kuten suojaavien pintaoksidien kehittäminen vaatii kuitenkin syvällistä tuntemusta hapettumisprosessista ja toisaalta myös normaaliolosuhteissa materiaalissa esiintyvien hilavirheiden vaikutuksesta siihen. Tässä työssä keskitytäänkin tutkimaan juuri niitä mekanismeja, joilla erilaiset pintavirheet ja porrastettu pintarakenne vaikuttavathapen adsorptioprosessiin kuparipinnalla. Tutkimus on tehty käyttämällä laskennallisia menetelmiä sekä VASP- ja SIESTA-ohjelmistoja. Työssätutkittiin kemiallisia ja rakenteellisia virheitä Cu(100)-pinnalla, joka on reaktiivisin matalanMillerin indeksin pinta ja porrastetun pinnan tutkimuksessa käytettiin Cu(211)-pintaa, joka puolestaan on yksinkertainen, stabiili ja aiemmissa tutkimuksissa usein käytetty pintarakenne. Työssä tutkitut hilavirheet, adatomit, vähentävät molekyylin dissosiaatiota kuparipinnalla, kun taas vakanssit toimivat dissosiaation keskuksina. Kemiallisena epäpuhtautena käytetty hopeakerros ei estä kuparin hapettumista, sillä happi aiheuttaa mielenkiintoisen segregaatioilmiön, jossa hopeatyöntyy syvemmälle pinnassa jättäen kuparipinnan suojaamattomaksi. Porrastetulla pinnalla (100)-hollow on todennäköisin paikka molekyylin dissosiaatiolle, kun taas portaan bridge-paikka on suotuisin molekulaariselle adsorptiolle. Lisäksi kuparin steppipinnan todettiin olevan reaktiivisempi kuin tasaiset kuparipinnat.

Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics

Purpose: To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. Patients and methods: A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Results: Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was 1,407 ( 897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. Conclusion: LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.

Regulation of Rat and Human T-cell Immune Response by Pharmacologically Modified Dendritic Cells.

BACKGROUND: The central function of dendritic cells (DC) in inducing and preventing immune responses makes them ideal therapeutic targets for the induction of immunologic tolerance. In a rat in vivo model, we showed that dexamethasone-treated DC (Dex-DC) induced indirect pathway-mediated regulation and that CD4+CD25+ T cells were involved in the observed effects. The aim of the present study was to investigate the mechanisms underlying the acquired immunoregulatory properties of Dex-DC in the rat and human experimental systems. METHODS: After treatment with dexamethasone (Dex), the immunogenicity of Dex-DC was analyzed in T-cell proliferation and two-step hyporesponsiveness induction assays. After carboxyfluorescein diacetate succinimidyl ester labeling, CD4+CD25+ regulatory T-cell expansion was analyzed by flow cytometry, and cytokine secretion was measured by ELISA. RESULTS: In this study, we demonstrate in vitro that rat Dex-DC induced selective expansion of CD4+CD25+ regulatory T cells, which were responsible for alloantigen-specific hyporesponsiveness. The induction of regulatory T-cell division by rat Dex-DC was due to secretion of interleukin (IL)-2 by DC. Similarly, in human studies, monocyte-derived Dex-DC were also poorly immunogenic, were able to induce T-cell anergy in vitro, and expand a population of T cells with regulatory functions. This was accompanied by a change in the cytokine profile in DC and T cells in favor of IL-10. CONCLUSION: These data suggest that Dex-DC induced tolerance by different mechanisms in the two systems studied. Both rat and human Dex-DC were able to induce and expand regulatory T cells, which occurred in an IL-2 dependent manner in the rat system.

Community replacement of neritic carbonate organisms during the late Valanginian platform demise: A new record from the Provence Platform

The Valanginian is marked by a major platform demise inducing a hiatus in the northern Tethyan neritic carbonate record from the top of the lower Valanginian to the lower Hauterivian. New biostratigraphic and chemostratigraphic data from the Ollioules section (Provence Platform, southern France) are presented here, demonstrating that a large part of the upper Valanginian is preserved in an inner platform environment. The thick, upper Valanginian, aggrading carbonate succession is observed in an aborted rift domain, implying relatively low subsidence. In this context, a relatively long-term sea-level rise was required to sustain a keep-up style of carbonate production. Like the Apulian Platform, the remarkable preservation of the Provence Platform may have been favored by its remoteness from terrigenous source areas, as suggested by the low clastic inputs and low P-accumulation rates. Two main biotic community replacements are observed in Ollioules. The first saw the development of abundant microbialites and algae at the onset of the late Valanginian. A Tubiphytes concentration occurred during the coolest climatic conditions and the transition towards arid conditions, whereas the subsequent Lithocodium-Bacinella and orbitolinids assemblages developed under low nutrient conditions during a warmer interval. Both assemblages may have been triggered by increased alkalinity. The second community replacement saw the installation of coral- and rudist-dominated communities during the latest Valanginian to early Hauterivian. They indicate a change to oligotrophic, open marine conditions. Six medium-scale sequences have been defined in Ollioules, indicating short-term transgressive-regressive trends superimposed on a long-term transgression. Low nutrient inputs and relatively low subsidence in an aggradational context may explain the survival of the isolated Provence Carbonate Platform during a time of widespread drowning episodes and platform demise in the northern Tethyan domain. (c) 2012 Elsevier B.V. All rights reserved.

Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients.

OBJECTIVES: To determine whether valganciclovir 450 mg every 48 h for cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in solid organ transplant recipients during continuous renal replacement therapy (CRRT). PATIENTS AND METHODS: Ganciclovir pharmacokinetics was intensively studied in two lung transplant recipients under valganciclovir 450 mg every 48 h over one dosing interval. In vitro experiments using blank whole blood spiked with ganciclovir further investigated exchanges between plasma and erythrocytes. RESULTS: Ganciclovir disposition was characterized by apparent total body clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir from red blood cells into plasma, increasing the apparent efficacy of haemofiltration. CONCLUSIONS: A valganciclovir dosage of 450 mg every 48 h appears adequate for patients under CRRT requiring prophylaxis for CMV infection, providing concentration levels in the range reported for 900 mg once daily dosing outside renal failure.

Varastonhallintakäytäntöjen kehittäminen maahantuontia harjoittavalle pienyritykselle

Työn tavoitteet liittyivät varastonhallintakäytäntöjen kehittämiseen sekä tämän seurantaan ja ylläpitoon liittyvien työvälineiden luomiseen. Päätutkimuskysymyksenä oli: 'Miten varastonhallintakäytäntöä kannattaisi parantaa, niin että nykyisillä resursseilla saavutettaisiin kustannussäästöjä asiakkaan palvelutasoa alentamatta?' Keskeinen teoreettinen sisältö liittyy varastonhallintakäytäntöihin. Tämä käsitellään varastonhallinnan perusteiden, varastonohjauksen, suorituskyvyn arvioinnin sekä varastonhallintakäytännön muutosprosessin avulla. Empiirinen osuus suoritetaan kohdeyrityksen logistisen muutosprosessimallin läpiviemisen avulla sisältäen tunnuslukuja, täydennysmenetelmiä, tuoteluokittelua ja muita analyyseja. Muutosprosessin vaiheet ovat edellytysten selvittäminen, nykytilan kuvaus ja analysointi, vaihtoehtoisten ratkaisujen ehdottaminen, nykytilan vertailu ratkaisuehdotelmiin, yhden ratkaisun valitseminen, muutoksen läpivienti ja lopputulosten seuranta. Työn keskeiset tulokset ovat erilaisten varastonhallintaan liittyvien tunnuslukujen laskeminen, tuoteluokittelun suorittaminen, täydennysmenetelmiin kuuluvien kaavojen luominen, varastokartan laatiminen ja toimintavaihtoehtojen esittely. Viimeiseen sisältyy oman muokatun kohdeyritykselle soveltuvan ¿voi tilata¿ täydennysmenetelmän laatiminen, ehdotuksen tekeminen liikkumattomien nimikkeiden eroon pääsemisestä, nimikkeiden uudelleensijoittaminen varastoon laaditun varastokartan mukaisesti, uuden työjaonluominen, muutosehdotuksen säännöllinen seuranta ja uusien tavoitteiden asettaminen sekä koulutustarpeeseen ja tietojärjestelmän kehittämiseen liittyvien ehdotusten tekeminen emoyhtiölle.

La biologie moléculaire est-elle utile au praticien [Is molecular biology useful to the practitioner?]

The relative importance of molecular biology in clinical practice is often underestimated. However, numerous procedures in clinical diagnosis and new therapeutic drugs have resulted from basic molecular research. Furthermore, understanding of the physiological and physiopathological mechanisms underlying several human diseases has been improved by the results of basic molecular research. For example, cloning of the gene encoding leptin has provided spectacular insights into the understanding of the mechanisms involved in the control of food intake and body weight maintenance in man. In cystic fibrosis, the cloning and identification of several mutations in the gene encoding the chloride channel transmembrane regulator (CFTR) have resolved several important issues in clinical practice: cystic fibrosis constitutes a molecular defect of a single gene. There is a strong correlation between the clinical manifestations or the severity of the disease (phenotype) with the type of mutations present in the CFTR gene (genotype). More recently, identification of mutations in the gene encoding a subunit of the renal sodium channel in the Liddle syndrome has provided important insight into the physiopathological understanding of mechanisms involved in this form of hereditary hypertension. Salt retention and secondary high blood pressure are the result of constitutive activation of the renal sodium channel by mutations in the gene encoding the renal sodium channel. It is speculated that less severe mutations in this channel could result in a less severe form of hypertension which may correspond to patients suffering from high blood pressure with low plasma renin activity. Several tools, most notably PCR, are derived from molecular research and are used in everyday practice, i.e. in prenatal diagnosis and in the diagnosis of several infectious diseases including tuberculosis and hepatitis. Finally, the production of recombinant proteins at lower cost and with fewer side effects is used in everyday clinical practice. Gene therapy remains an extraordinary challenge in correcting severe hereditary or acquired diseases. The use of genetically modified animal cell lines producing growth factors, insulin or erythropoetin, which are subsequently encapsulated and transferred to man, represents an attractive approach for gene therapy.