Thèses sur le sujet « Syringes »

The use of solid dispersions to formulate poorly water soluble drugs is a growing field in the pharmaceutical sciences. Hot-melt extrusion is a common method for producing dispersions. However, bench-top extruders require large amounts of powder to run and are inappropriate for early formulation screens. Plastic and glass syringes are readily available in most laboratories. 250 mg of drug-polymer blend is placed in a plastic syringe body that has the tip covered with a bent needle. The syringe is heated for 5 minutes and the extrudate is pushed through the syringe. Extrudates are characterized by differential scanning calorimetry and powder x-ray diffraction. Acetaminophen, griseofulvin, indomethacin, salicylamide, and sulfamethoxazole extruded with polyvinylpyrrolidone K12 match or exceed the performance of solvent evaporated controls. Glass syringes can be used when polymers have processing ranges above the melting point of the plastic syringes. Syringe extrusion is effectively demonstrated as a rapid process for early formulation screening.

Thesis (MBA)--Stellenbosch University, 2001.
ENGLISH ABSTRACT: Daily more than 300 000 health care workers in South Africa are to a lesser or greater extent exposed to the risk of deadly viruses which can be transferred through neediestick injuries. It is estimated that currently 9,8 million people in South Africa are HIV positive. This high incidence of HIV has a great impact on the danger of infection from neediestick injuries. It is estimated that 44 000 neediestick injuries takes place annually in South Africa. Despite such a high risk there are currently few safety regulations or official efforts to prevent or determine the true impact and incidence of needlesticks in South Africa. This study project investigated the number of neediestick injuries that could potentially be prevented by the use of needles with safety features and estimated the ranges of benefits and costs of using such safety devices. With the financial constraints that are imposed on South African hospitals, infection control through the use of safety syringes makes economic sense. Prevention of infections is clearly far cheaper than cure.
AFRIKAANSE OPSOMMING: Daagliks word meer as 300 000 gesondheids personeel in Suid Afrika in 'n mindere of meerdere mate blootgestel aan die risiko van lewens gevaarlike viruse wat deur middel van naaldprik ongelukke oorgedra kan word. Hierdie risiko word spesifiek in Suid Afrika verhoog deur die hoë insidensie van HIV. Dit word beraam dat daar tans 9,8 miljoen mense in Suid Afrika is wat HIV positief is. Daar word beraam dat daar tans 44 000 naaldprik ongelukke per jaar in Suid Afrika plaasvind. Ten spyte van die hierdie hoë risko is daar tans min veiligheids regulasies of amptelike pogings om die omvang en voorkoming van naaldprik insidente te bepaal nie. Hierdie studie het die getal naaldprikke wat voorkom kan word deur die gebruik van veiligheids inspuitnaalde ondersoek en het die voordele en kostes van sulke veiligheidsmaatreëls beraam. Gegewe die finasiële druk wat ons tans in Suid Afrikaanse hospitale ondervind, is bewys dat die gebruik van veiligheids inspuitnaalde ekonomiese sin maak. Voorkoming op hierdie manier is bewys as 'n ver goedkoper opsie as nasorg.

Oral vitamin K is administered to patients who have very high INR lab values and are on warfarin therapy. Due to the inability of some patients to swallow tablets, and the commercial formulation of vitamin K being available only as a tablet or an injectable emulsion, it may be necessary to compound an oral liquid formulation. When compounding batches of oral solutions, it is sometimes convenient to measure the product in unit doses. In this project, we compared liquid vitamin K in sterile water (1mg/mL) verses liquid vitamin K in Ora-Sweet (1mg/mL) stored in amber plastic syringes. Vitamin K is light sensitive and is best stored in amber containers. Vitamin K is also lipophilic and may adsorb to the plastic syringes. In this study, we investigated the feasibility of bulk compounding oral vitamin K solutions, and aliquoting them for storage in amber plastic syringes. The Vitamin K in sterile water syringes were made by mixing 45 mL of sterile water and 5 ampules, each containing 10mg/mL of vitamin K emulsion, together in an amber glass bottle for a final concentration of 1mg/mL. Thirty 1mL plastic amber syringes were filled with the mixture, capped, and placed in the refrigerator. The same process was repeated using Ora-Sweet instead of sterile water to fill thirty more plastic amber syringes. Three syringes of vitamin K in sterile water mixture, three syringes of vitamin K in Ora-Sweet mixture, and one Vitamin K reference standard were all analyzed using HPLC-UV on the day of compounding, and at day 1, 2, 4, 7, 14, 21, 30, 60, and 90. If stability is defined as 90-110% active ingredient, then Vitamin K in sterile water is stable to fourteen days, 95.3±3.5% recovery, but some samples fell below 90% recovery after 14 days. By day ninety, the recovery in SWFI syringes was 84.2±8.9%. For vitamin K in Ora-Sweet, the within-day variability was very high due to limitations in drug dissolution; as such the average concentration was not consistently above 90%. On the day of compounding, the percent recovery in the Ora-Sweet syringes was 92.7±9.9%, despite 1 hour of stirring. In conclusion, the Vitamin K in sterile water mixture can be stored in refrigerated, amber oral plastic syringes for 14 days, but plastic amber syringes were not appropriate for storage of the Vitamin K in Ora-Sweet mixture.

The purpose of this study was to evaluate the stability of vitamin K1 oral liquids in Sterile Water for Injection when stored in amber glass bottles and amber plastic syringes under refrigerated conditions. Four 100-mL batches of vitamin K1 in Sterile Water for Injection were prepared in amber glass bottles to protect from light. One of the batches was divided into 1-mL aliquots, using amber plastic oral syringes, and capped. The prepared bottles and syringes were stored in a laboratory refrigerator. On each day of sampling, 1-mL aliquots were removed from each bottle and mixed with an equal volume of ethanol. Likewise, the contents of sample syringes were mixed with ethanol to achieve an assay concentration of 0.5 mg/mL. Recovery of vitamin K1 in the compounded samples was quantified against a United States Pharmacopeia reference standard. Quantification was achieved using a stability-indicating high-performance liquid chromatography with ultraviolent light detection method. Product stability is defined as 90% to 110% of the initial concentration. The percent recovery in the Sterile Water for Injection preparations in glass bottles remained above 90% for the 105-day duration of the study, but some samples stored in amber plastic syringes fell below 90% on day 21. Furthermore, a statistically significant difference (2-way ANOVA, P < 0.0001) emerged between syringes at day 0 and day 30, and this trend continued through the day 60, 90, and 105 samples. The only statistically significant difference found within the bottle-stored samples occurred on day 105 (versus zero, P = 0.0465), but the recovery on day 105 still exceeded 90%. Vitamin K1 in Sterile Water for Injection, stored in a refrigerated amber glass bottle, is stable for 105 days. This preparation can also be stored in amber plastic syringes, but this decreases the beyond-use date to 14 days.

Background:Compounded vitamin K oral liquids may be useful in some patient populations, or when an appropriate solid dosage form is not available. While vitamin K oral liquid is typically prepared with sterile water for injection (SWFI), other compounding agents may be more palatable.Objective:To evaluate stability of compounded vitamin K liquids in SWFI, Ora-Sweet, simple syrup, cherry syrup, and SyrPalta stored in amber plastic oral syringes.Methods:Five types of compounded vitamin K liquids were prepared in triplicate—Ora-Sweet, simple syrup, cherry syrup, SyrPalta, and SWFI without flavoring; aliquoted into amber plastic oral syringes; and stored in a laboratory refrigerator (4.9°C to 5.4°C). On study days, 3 syringes from each batch were removed, diluted to assay concentration, and compared with a freshly prepared US Pharmacopeia reference solution. The samples and reference were analyzed using a previously validated high-performance liquid chromatography–ultraviolet method. Product stability was defined as 90% to 110% labeled amount. Results were further compared using a 2-way ANOVA (analysis of variance; P = .05) with post hoc Tukey’s correction for multiple comparisons.Results:Vitamin K in SWFI, SyrPalta, and cherry syrup was stable for 21 days, 7 days, and 24 hours, respectively, under refrigeration in amber plastic oral syringes. Vitamin K in Ora-Sweet and simple syrup demonstrated high within-day variability and low potency. Statistically significant differences were detected between the SWFI formulation and all other vehicles.Conclusion:Vitamin K in SWFI is appropriate for longer-term storage of unit-dosed vitamin K; however, SyrPalta and cherry syrup may be used for short-term storage or immediate administration of vitamin K.

Purpose: Vitamin K1 (phytonadione) is a fat-soluble vitamin and an essential cofactor for the synthesis of clotting factors II, VII, IX, X, protein C, and protein S. Vitamin K antagonists deplete vitamin K reserves effectively preventing the synthesis of these clotting factors leading to anticoagulation. Overly excessive anticoagulation, as evidenced by INRs greater than 5, may necessitate vitamin K for reversal of warfarin depending on bleeding risk factors. For elevated INR without bleeding, the oral route is preferred. Orally administered vitamin K1 tablets are only supplied by a single manufacturer, and only available as a 5 mg tablet. Concerns with availability of this tablet, lack of dosing options for treatment requiring less than 5 mg, and delivery options for patients unable to swallow whole tablets have prompted the exploration of alternative dosing strategies using the 10 mg/mL injectable emulsion compounded into an oral liquid. The possibility of storing the oral liquid in unit-doses adds a layer of convenience, and is common practice in many hospital pharmacies. In this project, we compared oral liquid vitamin K1 in sterile water for injection (SWFI) to oral liquid vitamin K1 in Ora-Sweet, simple syrup, cherry syrup, and Syrpalta stored in amber plastic oral syringes. Methods: Batches of 1 mg/mL vitamin K1 were prepared in SWFI, Ora-Sweet, simple syrup, cherry syrup, and Syrpalta and drawn up by 1-mL aliquots into amber plastic oral syringes. Syringes were capped and stored in a laboratory refrigerator (4.9-5.4oC). for the duration of the study. On each study day (0, 1, 2, 4, 7, 14, 21, 30, 60, and 90), three syringes from each vehicle were removed, and the contents diluted with ethanol to achieve a 0.5 mg/mL assay concentration. Additionally, USP reference material was used on each study day to prepare a fresh 0.5 mg/mL reference solution. The samples and reference were analyzed using a previously validated HPLC-UV method. Results were compared using a 2-way ANOVA (p = 0.05) with post-hoc Tukey’s correction for multiple comparisons. Product stability was defined as 90-110% labeled amount. Results: Of the vehicles tested, SWFI was the most suitable vehicle for longer-term storage of unit-dosed vitamin K1. The 1 mg/mL vitamin K1 in SWFI, when stored in amber plastic oral syringes, remains within the acceptable 90 – 110% range for 21 days. The Syrpalta preparation demonstrated the next highest BUD of 7 days, with one syringe (2 injections) falling outside the 90% potency at the 14 day time point. Cherry syrup allowed for very limited stability, with a BUD of 24 hours. By the 48-hour time point, two of the three samples were below the 90% potency cutoff. For the vitamin K oral solutions prepared in simple syrup and Ora-Sweet, the recovery of vitamin K was not within acceptable limits, even on the day of compounding. The initial recovery for vitamin K in simple syrup was only 86.8%. Similarly, the preparation in Ora-Sweet, was not at acceptable potency on the day of compounding, (92.7 ± 9.9%). While the average recovery in Ora-Sweet exceeded 90%, the variability between samples suggests a lack of homogeneous distribution of drug through the vehicle. Statistically significant differences were detected between the SWFI preparation and all other vehicles in a 2-way ANOVA with Tukey’s multiple comparison post-test (p-value of 0.05). This difference was most pronounced between SWFI and Ora-Sweet and SWFI and simple syrup (both p < 0.0001). Cherry syrup was also vastly different from SWFI (p = 0.0002), and the difference between SWFI and Syrpalta was less pronounced, yet still significant (p = 0.0442). Conclusion: Vitamin K1 in sterile water and Syrpalta was stable for 21 days and 7 days, respectively, when stored in amber plastic syringes. Vitamin K1 in cherry syrup was only stable for 24 hours in the syringes. For vitamin K1 in Ora-Sweet and simple syrup, the within-day variability was very high due to limitations in drug dissolution; as such the average recovery was not consistently above 90%, even on the day of compounding. Statistically significant differences were detected between the SWFI formulation and all other vehicles. Several factors appear to affect the potency and stability of vitamin K1 in different vehicles. Because the stability of vitamin K1 oral solution differs between storage in amber glass bottles and oral syringes, vitamin K1 may have the potential to adsorb to polypropylene (PPE). The pH of the vehicle may contribute to degradation of vitamin K1, and the viscosity of the vehicle may affect the achievable potency of certain mixtures. The viscosity of the mixture also appears to affect maintenance of a homogenous mixture, but the presence of alcohol in the vehicle may help aid in solubilizing the vitamin K1 in Syrpalta. Vitamin K1 in SWFI appears to be the most suitable vehicle for longer-term storage of unit-dosed vitamin K, but Syrpalta and cherry syrup may also be appropriate for more immediate use.

The purpose of this study was to evaluate the stability of two preparations of vancomycin oral solution in two different storage containers, capped amber oral-dosing syringes and heat-sealed oral-dosing cups, stored under refrigerated conditions. Commercially available grape-flavored vancomycin oral preparation and compounded vancomycin for intravenous use in cherry syrup oral preparation were divided into 5-mL aliquots into heat-sealed plastic dosing cups and capped oral-dosing syringes. All samples were stored under refrigeration (2°C to 8°C) and evaluated at days 0, 3, 7, 14, 30, 60, and 90. For each evaluation, samples were visually inspected and analyzed for potency using a stability-indicating high-performance liquid chromatographic method with ultraviolet detection. Over the study period, at least 90% of the initial concentrations for the preparation and the product in both storage containers were retained at 60 days. The commercially available oral vancomycin further demonstrated stability within 90% out to 90 days in the syringe and the unit-dose cups. Visual inspection revealed no changes in the grape-flavored vancomycin oral preparation, but a detectable red-dye precipitate could be seen in the crevices of the dosing cups from the vancomycin in cherry syrup oral preparation after 60 days. Commercially available grape-flavored vancomycin oral preparation was stable up to 90 days, and com- pounded vancomycin for intravenous use in cherry syrup oral preparation maintained stability for 60 days when dispensed in capped amber polypropylene oral-dosing syringes and heat-sealed plastic dosing cups when stored at refrigerated conditions.

Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Dr. Jonathan S. Colton; Committee Member: Dr. Mark R. Prausnitz; Committee Member: Dr. Rudolph L. Gleason. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Purpose:Omeprazole is a proton pump inhibitor (PPI) used in the treatment of gastrointestinal conditions, such as gastrointestinal esophageal reflux disease (GERD). Omeprazole is often prepared as an oral suspension to accommodate certain patients. Historically, oral suspensions of omeprazole were prepared using pharmaceutical compounding with sodium bicarbonate, but a kit for preparation of omeprazole oral suspension is available, FIRST® - Omeprazole. The purpose of this project is to compare the stability of the active pharmaceutical ingredient (API), omeprazole, in the FIRST® kit product to a traditionally compounded omeprazole suspension, when stored in refrigerated unit-dosed syringes. Methods: Five 100-mL batches of compounded omeprazole oral suspension (2 mg/mL) and five 300-mL kits of FIRST® - Omeprazole were prepared by a licensed pharmacist, and aliquoted into 5-mL doses in clear luer-lock plastic oral syringes, and stored at refrigerated temperature (2-8oC). Omeprazole concentration was assessed in each batch/kit on the day of preparation. Triplicate syringes from each batch/kit (n = 15 per test group per day) were removed after 7 days, 14 days, 21 days, and 30 days of refrigerated storage. Samples were diluted to assay concentration (1 mg/mL) in ion-free water and filtered using a 0.22-micron microcentrifuge filter tube. Samples were analyzed for omeprazole recovery using a validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method. Recovery was quantitatively assessed by comparing sample peak area to a freshly prepared calibration curve (1 – 0.125 mg/mL) using United States Pharmacopoeia (USP) reference standard on each day of sampling. Refrigerator temperatures were recorded daily using a digital thermometer. Results:Stability was defined as recovery of 90 - 110% of initial concentration of API. For the FIRST® - Omeprazole samples, the chemical potency remained within this window for the entire study period of 30 days. The compounded omeprazole suspension demonstrated a less than 90% average recovery at the day 21 sample. Furthermore, a statistically significant difference in the initial concentration was detected on the day of compounding (p = 0.0244), with the compounded omeprazole starting at 1.89 ± 0.10 mg/mL and the FIRST® - Omeprazole at 1.98 ± 0.04 mg/mL. After 30 days, the compounded omeprazole suspension had an 89.13% average API recovery (standard deviation; ± 5.17%) and the FIRST® - Omeprazole 97.20% API recovery (± 3.59%). Conclusion:Both traditionally compounded omeprazole suspension (2mg/mL) and FIRST® - Omeprazole suspension (2mg/mL) may be stored in clear luer-lock oral syringes under refrigeration for 14 days, and retain potency between 90 to 110% based on initial concentration. Furthermore, the FIRST® - Omeprazole suspension can be stored for the duration of the product’s beyond-use date of 30 days and retain potency between 90 to 110% of initial concentration or label claim. Finally, the data suggest that API concentration in FIRST® - Omeprazole suspension is more consistent from batch to batch than traditionally compounded omeprazole suspension.

Purpose: Oral vancomycin is a first-line treatment for Clostridium difficile-associated diarrhea. Preparation of oral vancomycin solutions historically has been facilitated by extemporaneous compounding, using various formulas or compounding kits, such as FIRST® - Vancomycin. More recently, FIRVANQ™ (vancomycin HCl) for oral solution was approved by the FDA, replacing the FIRST® compounding kits. Preparation and storage of unit-doses of oral solutions can expedite delivery of the medication to the patient and reduce opportunity for dosing errors. In this study, we evaluated the stored stability of two preparations of vancomycin HCl oral solution (FIRST® – Vancomycin and FIRVANQ™), stored in oral syringes and dosing cups at refrigerated and room temperatures. Methods: Triplicate batches of vancomycin HCl oral solution (50 mg/mL) were prepared using FIRST® - Vancomycin and FIRVANQ™, aliquoted into plastic oral syringes and sealed dosing cups, and stored at refrigerated and room temperatures for a total of six batches. Additionally, remaining samples from FIRVANQ™ batches were unit-dosed in clear Luer-Lok™ syringes and stored under refrigeration as a seventh batch. Samples were removed and analyzed for vancomycin recovery using a previously validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method over a 30-day period. Recovery was quantitatively assessed by comparing to a freshly prepared United States Pharmacopoeia (USP) reference standard on each day of sampling. Results: Stability was defined as recovery of 90 - 110% of labeled amount. For all tested samples, the chemical potency remained within the therapeutically acceptable window for the entire study period of 30 days. At room temperature, the FIRST® syringes and cups both retained 95% potency after 30 days. Under refrigeration, this product retained 100% potency and 91% potency in syringes and cups, respectively. Similarly, the FIRVANQ™ room temperature syringes were at 99% recovery and the room temperature cups at 95% recovery after 30 days. Refrigerated FIRVANQ™ retained a potency of 102% potency in the dosing cups after 30 days, and the both syringes types (clear and amber) were 97% and 101%, respectively, recovery during the study period. Conclusion: The percent recovery of vancomycin in each test group remains within 90 – 110% of the labeled amount throughout duration of study (0 – 30 days). Based on this study, unit-dosing has been shown to have a 30-day chemical stability. In this case, unit-dosing not only may be used to improve workflow and reduce dosing errors, but may also have an impact of reducing drug waste due to avoidance of discarding appropriately potent drug product. Additionally, stability within the study period was independent of storage container and condition. Finally, this unit-dosing practice for FIRVANQ™ is equally acceptable in the classic luer-slip amber plastic syringes, and the newer Luer-Lok™ clear plastic syringes.

O Diabetes Mellitus com suas complicações agudas e crônicas, é considerado um problema de saúde pública que compromete a produtividade, qualidade de vida e sobrevida dos indivíduos, envolvendo custos elevados para seu controle e terapêutica. A falta de fornecimento de materiais pode levar à prática de reutilização de seringas descartáveis para aplicação de insulina. Para conhecer melhor essa prática, optou-se por realizar este estudo que tem por objetivos descrever as características sócio-demográficas da população, avaliar a prática de aplicação de insulina, analisar a prática de reutilização, descrever as alterações mais freqüentes nos locais de aplicação e associá-las entre o Grupo A que reutiliza e o B que não reutiliza, associar as alterações mais freqüentes com o tamanho de agulha, número de aplicações de insulina fixa diária da população e relacionar o número de reutilizações com as alterações do Grupo A. O estudo é comparativo, analítico, transversal com abordagem quantitativa, foi desenvolvido no ambulatório de diabetes do Instituto da Criança do HCFMUSP. A população foi constituída de 199 pacientes (crianças e adolescentes) divididos em Grupo A que reutiliza seringas e Grupo B que não as reutiliza. A comparação das medianas de idade, tempo de doença e renda familiar entre os Grupos foi possível com o teste não paramétrico de Mann-Whitney. Os nódulos e lipohipertrofias foram comparados entre os Grupos através do teste de Fisher e para associar as complicações freqüentes com o tamanho de agulha, insulinas fixas diárias e número de reutilizações, foi usado o Qui-quadrado (2). Nas análises estatísticas foi adotado o nível de significância de 5%. O sexo feminino prevaleceu com 65,3%, a maioria provém de São Paulo capital (53,8%). A idade média do grupo A foi de 11 anos e do grupo B de 9 anos. O ensino fundamental sobressaiu-se com 51,3% nos pacientes e o fundamental incompleto 40,2% nos responsáveis. A média de renda familiar predominante foi de 1 a 2 salários mínimos 48,8%. A preferência pela seringa com agulha acoplada foi de 75,9%, compradas na farmácia (65,3%) com gasto mensal entre 20 a 79 reais (82,4%) ou seja, de 8 a 27 dólares. Um percentual de 55,8% pacientes auto-aplicam a insulina, preferem o álcool de supermercado para desinfecção da tampa do frasco (58,3%) e antissepsia da pele (57,3%). Lavam as mãos antes do preparo e aplicação da insulina 97,5%. Os locais preferidos para a injeção de insulina foram os braços (92%) e a coxa (82%), houve uma média de três aplicações no mesmo local em uma semana. A estratégia comum para reutilizar a seringa foi o reencape sem limpeza prévia (60,1%), guarda dentro (50,4%) ou fora da geladeira (49,7%) em um recipiente fechado (64,7%). A dor (39,2%) e outros motivos (38,6%) foram as causas para a troca da seringa. O hospital foi o local responsável pela orientação da reutilização em 52,3% e o enfermeiro em 34,6%. O local mais apontado para as complicações foi o braço para a presença de nódulos (61,3%) e de lipohipertrofias (52,8%). Não houve associação estatística entre as complicações com o tamanho da agulha e número de insulinas fixas diárias da população. Também não houve associação estatística entre o número de reutilizações com nódulos (p=0,185) e lipohipertrofias (p=0,841) do Grupo A. Os resultados desta pesquisa corroboram com os da literatura que apontam a baixa evidência de riscos de complicações pela prática de reutilização. Outras investigações envolvendo maior número de pacientes se fazem necessárias.
Diabetes Mellitus, with its acute and chronic complications, is considered a public health issue which compromises the productivity, quality of life and the individual survival, involving high costs for its control and therapeutic. The lack of material supply leads to the practice of reusing the discarded syringes in the insulin application. A study aiming at describing socio-demographic characteristics of the population, evaluating the practice of insulin application, analyzing the practice of the reuse, describing the most frequent alterations in the site of the application and associating these alterations with the size of the needle and the number of doses of daily fixed insulin between patients who reused the syringes and the ones who did not reuse them and associate the most frequent alterations in the site with the number of reuses, was performed in order to better know this practice. The study is comparative, analytical, transversal with a quantitative approach, and it was developed at the diabetes outpatient, Child’s Institute, Clinics Hospital, School of Medicine, University of São Paulo. The population was composed by 199 patients who were divided into two groups; Group A was composed by the ones that reused the syringes and Group B were the ones that did not reuse the syringes. The comparison of age, time of disease and family income medians between the groups was possible with the Mann-Whitney non parametric test. The nodules and lipohypertrophies were compared with Fisher test and the Chi-Square (2) test was used to associate the size of the needle and daily fixed insulin. The significance level of 5% was adopted in the statistical analysis. The female gender was predominant with 65.3%, majority of which comes from the city of São Paulo (53.8%). The average age was 11 years from Group A, and 9 years from Group B. A number of 51.3% of the patients had regular background and 40.2% of the responsible ones had an incomplete background, and the predominant average income family was from 1 to 2 minimum salaries 48.8%. The preference for the syringe with coupled needle was of 75.9%, bought at drugstores (65.3%) with monthly expenses between R$ 20 and R$ 79 (82.4%). A percentage of 55.8% of the patients self-applies the insulin, prefer the alcohol from supermarkets in order to decontaminate the cover of the bottle (58.3%) and perform the antisepsis of the skin (57.3%). They wash their hands before the preparation and the insulin application (97.5%). The preferable places to apply the insulin were the arms (92%) and the thighs (82%), and there was a mean of three applications in the same place in one week. The common strategy to reuse the syringe was the recap without a previous cleaning (60.1%), keep inside (50.4%) or outside the refrigerator (49.7%) in a closed recipient (64.7%). The pain (39.2%) and other motives were the cause for changing the syringe (38.6%). The hospital was the main site responsible for orienting the reuse in 52.3% and the nurse in 34.6%. The most reported place for complications was the arm due to the presence of nodules (61.3%) and lipohypertrophies (52.8%). There was neither statistical association of these complications between Groups A and B nor relation of the size of the needle and number of daily fixed insulin. There was also no statistical association between the number of reusing with nodules (p=0.185) and lipohypertrophies (p=0.841). The results of this research corroborate with the results of the literature, which point out the low evidence of risks of complications by the practice of reuse. Other investigations involving greater number of patients are necessary.

Syringopeptin (syp) and syringomycin (syr) are major necrosis-inducing lipodepsipeptide phytotoxins produced by P. syringae pv. syringae. This report demonstrates that syringopeptin production is activated by plant signal molecules. Syringopeptin production by BR132 was increased two-fold by addition of arbutin (100 µM) and D-fructose (0.1%) to syringomycin minimal medium (SRM). Subgenomic analysis of transcriptional expression with a 70-mer oligonucleotide microarray demonstrated that the syr-syp genes are induced 2.5- to 10.5-fold by arbutin and D-fructose. The syr-syp genomic island was found to be organized into 12 transcriptional units based on reverse transcriptional PCR (RT-PCR) and computer analysis. The transcriptional start sites of the salA gene and operons III and IV were located 63, 75, and 104-bp upstream of the start codons of salA, syrP, and syrB1, respectively, using primer extension analysis. The predicted -10/-35 promoter region of operon IV was confirmed based on mutagenesis analyses of the syrB1::uidA reporter with β-glucuronidase (GUS) assays. A 20-bp conserved sequence (TGTCccgN4cggGACA) with dyad symmetry around the -35 region was identified via computer analysis for the syr-syp genes/operons responsible for biosynthesis and secretion of syringomycin and syringopeptin. Expression of the syrB1::uidA fusion was decreased 59% when 6-bp was deleted from the 5’ end of the syr-syp box in the promoter region of operon IV. These results demonstrate that the conserved promoter sequences of the syr-syp genes contribute to the co-regulation of syringomycin and syringopeptin production. Microarray analysis established that the syr-syp genes responsible for synthesis and secretion of syringomycin and syringopeptin belong to the SyrF regulon. Vector pMEKm12 was successfully used to express both SalA and SyrF proteins fused to maltose-binding protein (MBP). Both MBP-SalA and MBP-SyrF fusion proteins were purified with maltose-affinity chromatography. Gel shift analysis revealed that the purified MBP-SyrF, but not the MBP-SalA fusion protein, bound to a 262-bp fragment containing the syr-syp box. Purified MBP-SalA caused the shift of a 324-bp band containing the putative syrF promoter. Gel filtration analysis or cross-linking experiments indicated that both SalA and SyrF form dimers in vitro. This study may provide an important perspective on the regulation of syringomycin and syringopeptin production.

Animals are commonly trained to perform behaviors during routine husbandry procedures. However, some husbandry procedures have aversive consequences when the real procedure is performed. This commonly results in loss of the trained behavior. The present study assessed whether maintaining the antecedent environmental stimulus conditions between appetitive and aversive outcomes would prevent this effect and, conversely, whether adding a stimulus discrepancy would facilitate this effect. Three domestic rats served as participants in a multiple baseline across participants design with multi-element components. All three rats stopped performing a trained behavior when a discrepant stimulus reliably predicted an aversive outcome. In addition, all three rats continued to perform the same behavior when antecedent environmental stimulus conditions were consistent between aversive and appetitive outcomes. Results are discussed in terms of practical implications for behavior change agents and conceptual implications for learning theory.

 Bakteriozno sušenje trešnje (Prunus avium L.) poslednjih nekoliko godina u mladim zasadima i plantažama trešnje predstavlja značajan problem u proizvodnji ove voćne vrste. Simptomi bolesti se ispoljavaju u vidu sušenja grana, grančica ili celih stabala, što se uglavnom zapaža na mestima rezidbe i oko pupoljaka, sa uočljivim promena boje tkiva kore, koje puca i nastaju rak rane. U periodu od 2012 – 2015 godine izvršen je monitoring zdravstvenog stanja trešnje kojim je obuhvaćeno nekoliko plantaža i manjih zasada trešnje iz više lokaliteta na području AP Vojvodine i centralne Srbije (Ritopek). Mlade voćke su očigledno najugroženije, jer smo na osnovu praćenja zdravstvenog stanja u više lokaliteta i zasadima različite starosti, pojavu bakterioznog sušenja u jačem ili slabijem intenzitetu, konstatovali samo u mladim zasadima (do 3 godine starosti – Selenča, Gornji Tavankut, Donji Tavankut, Ljutovo, Mikićevo i Kanjiža). Izolacijama na strandardne hranljive podloge, iz prikupljenih obolelih uzoraka trešnje, kao i sa zdravih pupoljaka i listova trešnje (epifitna populacija), dobijeni su brojni izolati bakterija P. syringae pvs. od kojih je za dalja ispitivanja odabrano 155 izolata. Identifikikacija dobijenih izolata je izvršena je na osnovu fenotipskih i genotipskih metoda. Na osnovu LOPAT testova izolati pripadaju Ia grupi fluorescentnih vrsta Pseudomonas syringae. Prema GATTa testovima utvrđene su dve grupe izolata u okviru vrste P. syringae: I grupa (G+A+T–Ta–) i II grupa (G–A–T+Ta+). Dodatni testovi su potvrdili GATTa testove, na osnovu kojih je zaključeno da sušenje mladih stabala trešnje prouzrokuju dve grupe bakterije P. s. pv. syringae (I grupa) i P. s. pv. morsprunorum rasa 1 (II grupa). Među ispitivanim izolatima nije bilo odstupanja u pogledu fenotipskih karakteristika u okviru iste grupe, osim sposobnosti stvaranja siringomicina pojedinih izolata I grupe (pv. syringae). Proverom patogenosti na raznim test biljkama i biljci domaćinu utvrđene su razlike, ali i određene sličnosti između izolata I i II grupe. Jasne razlike između grupa izolata utvrđene su pri inokulaciji zelenih plodova trešnje, višnje, ringlova i kruške, paradajza, paprike i mahuna boranije. Pri inokulaciji odvojenih listova jorgovana izolati I grupe (pv. syringae), kao i većina izolata II grupe (pv. morsprunorum rasa 1) su pozitivno reagovali, što ukazuje na heterogenost populacije bakterije P. s. pv. morsprunorum rasa 1. Pri inokulaciji sejanaca voćnih podloga (divlja trešnja, magriva, divlja šljiva, divlja kruška) svi izolati pv. syringae su prouzrokovali karakteristične patološke promene na podlogama svih voćnih vrsta, a izolati pv. morsprunorum rase 1 takođe na svim vrstama, osim na sejancima divlje šljive. Ovi rezultati ukazuju da je širenje bakterija moguće i putem podloga koje takođe mogu biti zaražene. Inokulacijama dvogodišnjih grančica trešnje u periodu mirovanja zaključeno je da su svi izolati pv. syringae i morprunorum rasa 1 podjednako patogeni na svim sortama trešnje (Burlat, Summit, Hedelfigenska i Germerzdorfska). Najveća dužina nekroze najčešće je zabeležena na sortama Burlat i Summit u kombinaciji sa izolatima I grupe (pv. syringae) u pojedinim slučajevima i sa izolatima II grupe (pv. morsprunorum rasa 1), a najmanja uglavnom kod sorti Germerzdorfska i Hedelfigenska sa izolatima II grupe (pv. morsprunorum rasa 1). Identifikacija izolata KBNS71 – 84 (Gornji Tavankut) i KBNS85 – 94 (Selenča) na bazi MLST korišćenjem gena gyrB, rpoD, gapA i gltA, jasno je pokazala prisustvo dva patovara P. s. pv. syringae i P. s. pv. morsprunorum rasa 1. Pri poređenju sa sojevima H – 1, V – 85, V – 88 (višnja) i V – 109 (trešnja) utvrđene su značajne razlike i postojanje genetskog diverziteta populacije ovih patogena. Simultana detekcija gena syrB i syrD utvrđena je kod 70 izolata I grupe (pv. syringae), a samo SyrB kod 9 izolata iste grupe (pv. syringae). Gen za sintezu koronatina detektovan je kod svih 76 izolata II grupe (pv. morsprunorum rasa 1). Rep – PCR metodom ustanovljene su značajne razlike (58%) između I i II grupe izolata (pv. syringae i pv. morsprunorum rasa 1). Ispitivani izolati sa trešnje u okviru pv. syringae nisu ispoljili međusobne razlike, ali se razlikuju od sojeva sa drugih lokaliteta i ranije izolovanih sa istog domaćina (V – 109 i T6), kao i od sojeva sa drugih domaćina – višnje (V – 85) i uljane tikve (Tk21) do 37%. Razlike među izolatima pv. morsprunorum rase 1 iznosile su manje od 5%, a 24% u odnosu na soj CFBP2119 istog patogenog varijeteta. Rep – PCR analiza ukazala je na nizak nivo heterogenosti ispitivanih izolata u okviru istog patogenog varijeteta. RAPD metoda, korišćenjem većeg broja prajmera, bila je uspešnija za poređenje ispitivanih izolata od rep – PCR. Od testiranih 11 prajmera, 4 (SPH1, DJP17, DJ15, DJ16) su selektovana za dalji rad na osnovu razlika među izolatima unutar patogenih varijeteta. Kumulativna RAPD analiza pokazala je da između ispitivanih izolata pv. syringae postoje razlike do 24%, a 41% u poređenju sa sojem KFB0103, dok su kod izolata pv. morsprunorum rase 1 razlike iznosile do 15%, a 36% u odnosu na soj4CFBP2119. Dobijeni rezultati RAPD analize ukazuju da u okviru populacije obe grupe ispitivanih izolata postoji određena heterogenost, ali je genetski diverzitet izraženiji kod pv. syringae. Proučavanjem epidemilogije ovih patogena u poljskim uslovima inokulacijom jednogodišnjih grana / mladara sortama Burlat, Germerzdorfska, Hedelfigenska i Droganova žuta, zaključeno je da trešnja u našim agroekološkim uslovima ranije postaje osetljiva (oktobar) prema P. s. pv. morsprunorum rasa 1 u odnosu na pv. syringae. Prvi pozitivni rezultati pri inokulaciji sojevima pv. syringae utvrđeni su pri inokulaciji u novembru. U pogledu dužine nekroze najuspešnije su bile novembarske inokulacije (najduže nekroze; 2,17 – 3,35 cm), uspešne su bile i januarske i martovske inokulacije, ali je dužina nekroze bila sve manja, respektivno. Generalno najduže nekroze su ostvarene kod sorte Burlat, a najkraće kod sorte Germerzdorfska. Sve inokulacije urađene u periodu vegetacije su bile negativne. Inokulacijama dvo – trogodišnjih grana na sorti Summit prve uspešne inokulacije (oba patovara) su ostvarene tek u novembru (oktobarske su bile negativne), kada je utvrđena i veća agresivnost patovara syringae. Pri inokulacijama u januaru dužina nekroze je bila manja, a martovska je bila negativna. Sve inokulacije vršene u periodu od bubrenja pupoljaka do opadanja lišća takođe su bile negativne. Ispitivanjem osetljivosti sotrimenta trešnje i pojedinih sorti višnje zaključeno je da su prema oba patovara (syringae i morsprunorum rasa 1) najosetljivije sorte trešnje Katalin, Linda, Summit, New Star i Burlat, srednje osetljive su sorte višnje Erdi Botermo i sorte trešnje Droganova žuta, CarmCarmen, Germerzdorfska i Rana od Noara, a slabo osetljive sorte višnje Španska i Ujfeheti firtoš i sorta trešnje Rita.
Bacterial die back (canker) of sweet cherry (Prunus avium L.) in young orchards and sweet cherry plantations in the past few years has been a significant problem in the production of this fruit species. Symptoms of the disease were manifested in the form of drying branches, twigs or whole trees, which were mainly observed in places of pruning or around the buds, bark changes a color, cracks and cankers has formed. In the period 2012 - 2015 monitoring of the health status of sweet cherries was carried out covering several plantations and smaller orchards of sweet cherries in several localities in Vojvodina and central Serbia (Ritopek). Young fruit trees are obviously the most susceptible, based on monitoring of the health status in many localities and plantations of different ages, the occurrence of bacterial canker in a stronger or weaker intensity was found only in young plantations (up to 3 years old - Selenča, Gornji Tavankut, Donji Tavankut, Ljutovo, Mikićevo and Kanjiža). From collected diseased samples of sweet cherries, as well as healthy buds and leaves of sweet cherry (epiphytic population) isolations on standard nutrient medium, were obtained numerous isolates of P. syringae pvs. and for further investigations was selected 155 isolates. Identification of isolates was performed on the basis of phenotypic and genotypic methods. Based on LOPAT tests isolates belonging to Ia group fluorescent Pseudomonas syringae. According to GATTa tests two groups of P. syringae isolates were identified, I group (G+A+T-Ta-) and II group (G-A-T+Ta+). Additional tests confirmed the GATT tests, on the basis which it was concluded that the drying of young sweet cherry trees caused P. s. pv. syringae (I group) and P. s. pv. morsprunorum race 1 (II group). Among the tested isolates was not exceptions in phenotypic characteristics within the same group, except for the ability to produced syringomycine for some isolates of I groups (pv. syringae). In pathogenicity tests on various plants and host plant were observed differences, but also and some certain similarity between isolates of I and II groups. Clear differences between the groups of isolates were determined in the inoculations of green fruit of sweet cherry, sour cherry, cherry plum and pears, tomatoes, peppers and green bean pods. In the case of inoculation of separate lilac leaves isolates of I group (pv. syringae) and most isolates of II group (pv. morsprunorum race 1) reactions were positive, what indicating the heterogeneity of the population of P. s. pv. morsprunorum race 1. In the inoculation of fruit rootstock seedlings (wild cherry, Magriva, wild plum, wild pear) all isolates pv. syringae caused the characteristic pathological changes on the all fruit species, isolates of pv. morsprunorum race 1 also except on the seedlings of wild plum. These results suggest that the spreading of bacteria is possibly through the rootstock that can also be infected. Inoculations of two – years old branches of sweet cherry during dormancy, was concluded that all isolates pv. syringae and morprunorum race 1 were equally pathogenic in all sweet cherry cultivars (Burlat, Summit, Hedelfigen and Germersdorf). The longest length of necrosis usually was observed on the cultivars Burlat and Summit in combination with isolates of I groups (pv. syringae), in some cases with isolates of II group (pv. morsprunorum race 1), and the lowest mainly in cultivars Germersdorf and Hedelfigen with isolates of II group (pv. morsprunorum race 1). Identification of isolates KBNS71 - 84 (GornjiTavankut) and KBNS85 - 94 (Selenča) based on MLST using genes gyrB, rpoD, gapA and gltA genes clearly showed the presence of two patovars P. s. pv. syringae and P. s. pv. morsprunorum race 1. Comparison with strains H - 1, V - 85 V - 88 (sour cherry) and V - 109 (sweet cherry) showed significant differences and the existence of genetic diversity in the population of these pathogens. Simultaneous detection of syrB and syrD gene was found in 70 isolates of I group (pv. syringae) and only syrB gene in 9 isolates of the same group (pv. syringae). The gene for coronatine synthesis was detected in all 76 isolates of II group (pv. morsprunorum race 1). Rep - PCR method detected significant differences (58%) between isolates of I and II groups (pv. syringae and pv. morsprunorum race 1). The tested isolates from sweet cherry within pv. syringae did not show differences between them, but they were different from the strains from other locations and previously isolated from the same host (V - 109 and T6), as well as strains from other hosts - cherry (V - 85) and pumpkin (Tk21) to 37 %. The differences between isolates pv. morsprunorum race 1 were less than 5% and 24% compared to the same pathovar strain CFBP2119. Rep - PCR analysis indicated a low level of heterogeneity of isolates within the same pathovar. RAPD method using a large number of primers were more successful to compare isolates than rep - PCR. Among 11 tested primers, 4 (SPH1, DJP17, DJ15, DJ16) were selected for further work on the basis of the difference between isolates within same pathovar. Cumulative RAPD analysis showed up to 24% differences among tested isolates of pv. syringae and 41% compared to the strain KFB0103, while among isolates pv. morsprunorum race 1 differences were 15% and 36% compared to the strain CFBP2119. The results of RAPD analysis indicate that a certain heterogeneity7exists in the population of both tested groups of isolates, but genetic diversity is more pronounced among isolates of pv. syringae. Studying the epidemiology of this pathogen in field conditions, by inoculating one – year old branches / or shoots sweet cherry cultivars Burlat, Germersdorf, Hedelfigen and Droganova žuta, it was concluded that the sweet cherry in our agroecological conditions becoming sensitive (October) to P. s. pv. morsprunorum race 1 before in relation to the pv. syringae. The first positive results of inoculations with strains pv. syringae were determined in November. Regarding the length of necrosis most successful were inoculation in the November (necrosis longest; 2.17 to 3.35 cm), inoculations also were successful in the January and the March, but the length of necrosis was smaller, respectively. Generally longest necrosis were observed in the cultivar Burlat, and the shortest in cultivar Germersdorf. All inoculations carried out in the period of vegetation were negative. Inoculations of two – three – years old branches of the cultivar Summit, first successful inoculations (for both pathovar) were observed only in November (October was negative), when a greater aggressiveness of pathovar syringae were determined. In inoculations in January length of necrosis was smaller, and in March was negative. All inoculations carried out in the period from buds swelling to leaf falling were also negative. Investigation susceptibility of sweet cherry and some sour cherry cultivars was concluded that against to both pathovars (syringae and morsprunorum race 1) the most susceptible were cultivars of sweet cherry Katalin, Linda, Summit, New Star and Burlat, medium susceptible were cultivar of sour cherry Erdi Botermo and sweet cherry cultivars Droganova žuta, Carmen, Germersdorf and Rana od Noara and low susceptible cultivars of sour cherry Španska and Ujfeheti firtoš and cultivar of sweet cherry Rita.

The aim of this study is to evaluate the supply of markers for the identification of syringes distributed by pharmacy needle exchanges and to determine if this product and service delivery offers a feasible method of marking syringes to promote the reduction of accidental sharing of syringes and needles amongst injecting drug users (IDU) and thereby reduce the risk of transmission of blood borne viruses (BBVs) and other related infections. This study involves the assessment, implementation and evaluation of syringe markers as a pilot study within three community pharmacy sites in Glasgow. The secondary aims of the study were to identify whether the supply of syringe markers from community pharmacy needle exchanges was acceptable to IDU and if it enabled them to mark their syringes. The literature review demonstrates that providing a means of identification of personal injecting equipment has been proposed as a viable option that should be promoted to prevent the inadvertent accidental sharing of syringes within a group setting. Needle exchanges (NEX) are important component parts of the harm reduction responses designed to reduce the physical health harms caused to individuals through injecting drug use. The literature is reviewed on BBV transmission and the historical, legal and policy context associated with the development of NEXs. Community pharmacies act as a source of health advice and can help to facilitate access to treatment services for those attending the NEX. However the specific aim of this study is not to investigate the totality of the benefits of a NEX but to examine the supply of a potential means of reducing accidental and unintentional sharing of all injecting equipment and thereby contribute to minimising some of the health harms linked to injecting drug use. Three established community pharmacies were identified as suitable sites to pilot the supply of syringe markers. A number of criteria were used to select the sites. These included an assessment of the geographic locations, staffing arrangements, NEX attendances and transactional activity and the availability of private consultation facilities. The health board central database which holds records on a range of factors including, the characteristics of those who attend NEX and detailed information on all transactions, was used to identify the most suitable sites to pilot the new intervention. This indicated that the characteristics of those who attended the three chosen sites were broadly similar to the wider NEX attending population. The evaluation was conducted in two separate periods. The first 4 week period was the supply phase where markers were distributed over this period to all patients receiving NEX packs from the 3 pharmacies. The second data collection phase was undertaken in the following 4 week period. Data was collected by means of a structured questionnaire. In order to reduce the potential interviewer bias it was decided to incorporate the use of peer researchers in the administration of the questionnaire. The Scottish Drugs Forum (SDF) was approached and agreement was reached to use members of the Service User Involvement Group (SUIG) to assist with the design and administration of the questionnaire. A submission was made to the health board Research Ethics Committee (REC) and approval was given to enable the study and the research evaluation to proceed. Before the start of the study, joint briefing and training sessions were held for pharmacy staff from the 3 sites and the 6 participating SUIG members. A total of 177 questionnaires were completed during the second data collection phase of the evaluation. Information was collected on personal details and injecting behaviours (including deliberate and accidental sharing), any current means of syringe identification, use of the markers and on the usefulness of the instruction card. Most individuals (75%, n=132) had been supplied with the markers to trial during the first supply phase of the study with 63% of the 132 (n=83) of those individuals reporting use of the markers. The results of the evaluation and subsequent analysis of the findings indicated that the syringe marker supply could be successfully implemented using pharmacy NEXs. The product and the supply method were acceptable to both staff and service users. Initial bivariate analysis was conducted using a number of dependent and independent variables identified within the questionnaire. These findings highlighted a number of areas worthy of further exploration, including emerging differences between male and female respondents, and indicated specific target groups for future developments in syringe identification. The contribution of the peer researchers was found to be a significant factor in successfully completing the evaluation. However it is not possible to make any definitive statements on how effective the intervention is in terms of reducing the transmission of BBVs and other related infections. The findings of the evaluation indicated a number of potential areas of work that could be usefully explored to investigate the effectiveness of the markers in reducing the transmission of infections. The limitations of the evaluation became apparent during the course of the study and the implications of these limitations are discussed.

Miniature products and components are in great demand in the electronics industry and Direct Write (DW) has become the subject of interest due to its capability of printing small features and offering low manufacturing cost. DW technologies, a subset of rapid prototyping, have been applied to many applications in electronics, aeronautics, photonics and biomedical engineering, Among them, syringe deposition technology is a promising technique, providing precision deposition of materials with various viscosities, on-line design changes and ability to write on non-planar substrates, In addition, the low amount of material waste, low cost investment in production facilities and the versatility of the system make syringe-based DW technology ideal for low-cost electronics production especially for small batch production, Furthermore, the data-driven nature of digital printing manufacturing methods allows fast manufacturing runs and a short time cycle from design to manufacture which all translate into shorter delivery times in manufacturing. Syringe-based DW technology is a new and promising technology and hence its capabilities have never been exploited comprehensively. The objective of this project was to investigate the possible use of a syringe-based DW technology by means of automatic syringe deposition system in conjunction with heating process to fabricate electronic components such as strain gauges, antenna and others. By doing this, the aim is to help improve the fundamental knowledge of syringe-based DW process behaviour and functional performance of components produced.

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering; in conjunction with the Leaders for Global Operations Program at MIT, 2010.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 69-70).
The primary goal for the thesis is to develop a recommendation for Amgen's future prefilled syringe strategy related to its drug process development, supplier relationship management plan, supply and sourcing, and procurement. The goal is achieved 1) by analyzing the historic growth drivers in the market and current market trends including changes and challenges, 2) by developing an analytical tool to understand complicated market dynamics between suppliers and buyers, 3) by developing a few future scenarios on how the market will evolve based on former analyses and models and 4) by developing and finalizing a recommendation for Amgen's future strategy. The prefilled syringe market is uniquely interesting for several reasons: 1) the prefilled syringe is an important primary drug container to both biotechnology and pharmaceutical companies, 2) there has been only one dominant supplier in the US, 3) biotech has been challenged with quality issues related to prefilled syringes and required the highest quality standards of syringe suppliers, 4) biotech's stringent quality standards and relatively low volume, compared with other big therapeutic classes such as anti-coagulants (heparins) and vaccines, can make it less attractive for the suppliers to align to biotech's needs, 5) new launch of advanced auto-injection device requires even higher prefilled syringe quality standards, and 6) the market is reshaping rapidly these days. First, the thesis analyzes the prefilled syringe market's history, major growth drivers, key suppliers and buyers, and market dynamics featuring key players. Secondly, it turns to discuss the challenges and issues Amgen has faced with these days and the backgrounds. Thirdly, it develops recommendations regarding Amgen's decisions on single versus multi sourcing, supplier selection, and supplier relationship structures. Lastly, it should be noted that all views, opinions, and assertions made in this thesis are those of the author alone, not of Amgen.
by Joonhaeng Lee.
S.M.
M.B.A.

People who inject drugs (PWIDs) are the most stigmatized and marginalized people in the general population (Ahern, Stuber, & Galea, 2007; Birtel, Wood, & Kempa, 2017). This group is not easily accessed by typical means of patient outreach and is one of the most underserved populations for primary care, mental health services, and care for chronic infectious diseases associated with injection drug use including HIV and HCV (Ahern et al., 2007; Dean et al., 2000; Livingston, Milne, Fang, & Amari, 2012; Zeremski et al., 2013). Syringe Service Programs (SSPs) can give public health and social support organizations and agencies access to an otherwise underserved population and give PWID potential access to a constellation of care to address multiple comorbidities associated with injection drug use (Barocas et al., 2014; Pollack, Khoshnood, Blankenship, & Altice, 2002; Zeremski et al., 2013). Additionally, the potential access to primary and secondary care that SSPs may connect PWID to, perceived social support is one of the strongest predictors of well-being and mental health among people with stigmatized conditions including HIV/AIDS, HCV, and PWID (Birtel et al., 2017). Wider adoption of SSPs and bridging of SSP clients to Medication Assisted Treatment providers is a potential tool in combating the current opioid epidemic in Tennessee. The Tennessee Poll by ETSU was conducted between March and April of 2017. The Tennessee Poll is an annual statewide public opinion poll conducted by the Applied Social Research Lab (ASRL). In the Tennessee Poll, questions were asked about attitudes and beliefs associated with SSPs and PWID in Tennessee. In a previous project, the research team, using generational demographic categories used in Pew surveys, looked at attitudes about both illicit and medical use of marijuana. In comparison of generations, Millennials were 15.62 times (95% CI 5.6, 43.56, p < .001) more likely to support recreational marijuana legalization versus the reference category (The Silent Generation or the generation before Baby boomers and sometimes called “The Greatest Generation”) and 3.7 times (95% CI 1.47, 9.3, p

Horizontal gene transfer (HGT) and gene loss are important processes in the evolution of prokaryotic lineages. HGT involves the movement of genetic material between distantly related species, and can facilitate adaptation when gained genes confer advantageous phenotypes to recipient lineages. However, high levels of gene gain and loss are predicted to obfuscate patterns of vertical descent and homogenise nucleotide diversity across ecological and phylogenetic boundaries. Thus, a holistic understanding of the role of genome fluctuation in the emergence and maintenance of genetically and ecologically cohesive bacterial groups remains to be fully elucidated. In this thesis, I use the plant-associated bacterium Pseudomonas syringae as a model system to investigate the impact of HGT and gene loss on evolutionary processes such as adaptation, diversification and speciation. The Gram-negative Gammaproteobacterium P. syringae is an opportunistic plant pathogen, and has been used for decades as a model system with which to study the interaction between plants and their microbial pathogens. Recently, the diversification of lineages within this species has involved a number of host jumps onto a range of woody host plant species, resulting in the emergence of diseases such as bacterial canker of kiwi and bleeding canker of the European horse chestnut. Using whole-genome sequence data and a range of comparative genomics and phylogenetics methods, I quantitatively reconstruct the history of gene gain and loss in P. syringae and show HGT to be the predominant evolutionary force in this species. Genomes of this species are under constant permutation, are subject to a highly diverse HGT genepool and show marked differences in patterns of codon usage between imported and core genes. I then generate additional genome data for 26 strains of P. syringae that are pathogenic on a range of different woody plants, and investigate the contribution from HGT to the adaptation of these strains into the woody niche. Using a method that accounts for the underlying phylogenetic relationships among P. syringae strains, I look for the correlated evolution between gained genes and the woody niche, and find that a substantial proportion of the genome is associated with this ecological niche. I then investigate the recent adapitation of P. syringae pv. aesculi onto the European horse chestnut, and show that a number of genomic events that include both homologous and non-homologous recombination are likely to have led to the evolution of this bacterium onto its host, where it has become the causal agent of the bleeding canker disease that is currently epidemic across much of northern and central Europe. Overall, this thesis is an investigation into how HGT contributes to niche adaptation in P. syringae, and aims to further our understanding of the mechanisms that underlie bacterial evolution.

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.
Includes bibliographical references (leaf 46).
At MD Company (Singapore), the syringe value stream faces escalating labor cost and high labor turnover. Two labor allocations were proposed previously to optimize current labor resources, with the aim of controlling the labor cost effectively without affecting the production. Proposal Two, which had demonstrated significant increase in productivity and reduced labor cost through computer simulations, entailed an addition of two workers each in the new dedicated inspector and material handler job designations. The associated new job scopes combine tasks which are currently assigned broadly to production technicians working on the syringe production floor. A work study approach was undertaken with the broad aim of reducing waste from the new job scopes, as well as to verify headcount used in the simulation of Proposal 2. Dedicating tasks to individuals presented opportunities to reduce repetition and to achieve collective savings via changes in methods. Within the work study, a method study provided a theoretical basis of how best to carry out the new job scopes, while a time study established time needed to perform a given set of tasks. Results found were consistent with that from simulation of Proposal 2. Further improvements were made in reducing inspection cycle time through streamlining of inspections. Identification and separation of tasks which are not performed constantly paved the way for one of the two material handlers to be hired on an overtime basis. Future iterative identification of waste and its removal could help current work converge to an optimal work standard.
by Gar Yan Ng.
M.Eng.

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.
Includes bibliographical references (leaf [53]).
At MD Medical (Singapore), the syringe value stream is facing escalating labor cost and high labor turnover. Therefore, optimization of the current labor resources is necessary to control the labor cost effectively without affecting the production capacity in order to stay competitive in the global context. A method used to design optimized labor allocations is outlined. Labor tasks were first categorized based on skill levels to form new job scopes. Following which, two new labor allocations were proposed. Both proposals feature flexible worker systems that reduce the response time to machines failures, as well as more focused job scopes to minimize work interruptions. New labor allocations facilitate the implementation of a skill-based pay system, which motivates employees to learn new skills. These two proposals can provide the benefits of higher production output and improved resource utilization.
by Xiangyong Su.
M.Eng.

Blast of pear caused by Pseudomonas syringae pv. syringae is one of the bacterial disease that limit pear production throughout the world. Symptoms are characterized by blast of buds and blossoms wich causes significant loss of fruit production, and necrotic spots on leaves or fruits. Control of bacterial blast of pear with chemicals is difficult and is based on copper compounds and antibiontics. However, its use is limited by the low efficacy, phytotoxicity to the plant or emerging resistance of the pathogen. The activity of several phosphonates (fosetil-Al, potassium phosphonate, etephon and fosfomycin) for control of P. syringae pv. syringae infection on pear was determined in this work, and laboratory models for studying P. syringae pv. syringae-pear interaction were developed
Pseudomonas syringae pv. syringae és un bacteri que ha estat descrit com agent causant de diverses malalties en més de 200 especies vegetals. En perera causa la necrosi bacteriana, que afecta la majoria de zones productores de pera del món, provocant un debilitament dels arbres i una disminució de la productivitat. En el treball que es presenta s'ha determinat l’activitat de diversos fosfonats (fosetil-AI, fosfonat potàssic, etefon i fosfomicina) en el control de la infecció per P. syringae pv. syringae en perera. Per això s'han desenvolupat models d'estudi de la interacció P. syringae pv. Syringae-perera i s'han determinat els factors que afecten la interacció. Aquests models de laboratori, com que han permès conèixer aspectes concrets de la interacció hoste-patogen i definir de forma clara el tipus d'interacció, s'han aplicat a l'estudi de l'activitat dels fosfonats en la interacció P. syringae pv. syringae -perera i en el control de la malaltia

An RND (resistance-nodulation-cell division) transporter, called the PseC protein, was identified at the left border of the syr-syp genomic island of Pseudomonas syringae pv. syringae strain B301D. The PseC protein exhibited amino acid homology to a putative RND transporter of Ralstonia solanacearum with identities of 61% (i.e., PseC). The pseC mutant strain showed a larger reduction in syringopeptin secretion (67%) than syringomycin secretion (41%). A β-glucuronidase assay with a pseA::uidA reporter construct indicated that the GacS/A two-component system controls expression of the pseA gene. Expression of the sypA gene by mutant strain B301D-HK4 corresponded to approximately 13% of that by parental strain B301D, whereas the syrB1 gene expression by mutant strain B301D-HK4 was nearly 61%. Mutant strain B301D-HK4 was reduced in virulence by about 58% as compared to parental strain B301D. A drug-supersensitive acrB mutant of E. coli showed increased resistance to acriflavine and tetracycline upon heterologous expression of the pseA, pseB, and pseC genes. Thus, the PseC protein, an RND transporter, has an important role in secretion of syringomycin and syringopeptin. An ATP-binding cassette (ABC) transporter, called the PseF protein, was identified at the left border of the syr-syp genomic island. The PseF protein exhibited amino acid homology to a putative ABC transporter of E. coli W3104 with identities of 57.6% (i.e., PseF to MacB). The pseF mutant strain showed significant reduction in secretion of syringomycin (74%) and syringopeptin (71%). Expression of the sypA gene by mutant strain B301D-HK7 was approximately 6.9% as compared to that of parental strain B301D, while the syrB1 gene expression by mutant strain B301D-HK7 was nearly 14.6%. Mutant strain B301D-HK7 was less virulent by approximately 67% than parental strain B301D. Expression of the pseF gene was induced approximately six times by strain B301D grown on SRMAF, as compared to that of strain B301D grown on SRM. During infection of bean plants by P. syringae pv. syringae strain B728a, expression of the pseF gene increased 3 days after inoculation. Thus, the PseF protein, an ABC transporter, responsible for secretion of syringomycin and syringopeptin is required for full virulence.

Precipitation over the eastern United States has been increasing in acidity, particularly within the last three decades. The average annual pH of rain in this area is about 4.2. The foliar surface, or phylloplane, of soybean can be damaged by rain acidified to pH 2.9. Simulated acidic precipitation has an overall inhibitory influence on soil microbial processes. The effect acidic precipitation may have on epiphytic microorganisms has not been examined. Bacteria are among the most numerous residents on the phylloplane.

Master of Science

Nitric oxide (NO) and S-nitrosothiols (SNOs) are widespread signalling molecules that regulate immunity in animals and plants (Wendehenne et al., 2001). Previously, we have reported that Arabidopsis thaliana S-nitrosoglutathione reductase, (AtGSNOR1) modulates the extent of total cellular SNO formation, which subsequently regulates multiple modes of plant disease resistance (Feechan et al., 2005). Loss-of-function mutations in AtGSNOR1, leading to increased SNO levels, have recently been shown to result in S-nitrosylation of the key defence regulators NPR1 and AtSABP3, blunting their activity and subsequently leading to increased pathogen susceptibility (Tada et al., 2008; Wang et al., 2009). Thus, inhibiting AtGSNOR1 function leading to increased SNOs, would potentially provide a good strategy for bacterial effector proteins, delivered by the type III secretion system (TTSS), to promote infection. AtGSNOR1 is constitutively expressed in all organs in Arabidopsis and its expression is induced by wounding stress avirulent and non-host pathogen. Using gas phase chemiluminescence, we show that infection with Pseudomonas syringae pv. tomato strain DC3000 (PstDC3000) resulted in increase SNO levels which is TTSS. At the same time, RT-PCR and GUS analysis indicated that AtGSNOR1 expression was transiently suppressed by PstDC3000 which is also TTSS-dependent. Therefore, PstDC3000 infection suppresses denitrosylase function of AtGSNOR1 to increase SNO levels and this virulence effect is delivered by at least one of the effector protein secreted through TTSS. Several putative cis-acting elements were identified in AtGSNOR1 promoter through deletion analysis including GT-box, W-box and MYB/MYC binding motif. These elements comprise of positive and negative regulators which are critical for the induction and suppression of AtGSNOR1 in response to pathogen infection. A few transgenic plants expressing effector proteins were selected and tested for their suppressive effect on AtGSNOR1 expression during PstDC3000 infection. HopAM1 effector proteins showed the ability to suppress AtGSNOR1 when expressed in planta.

The apoplast is the site of infection for many important bacterial crop pathogens, including the model pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). The chemical environment within the plant apoplast can determine the outcome of bacterial infection and the composition of this compartment is known to change in response to the presence of invading organisms. However, this metabolically dynamic environment has received little attention in the literature, and even less is known about how metabolites in the apoplast influence the expression of virulence genes. In this study, several aspects of the metabolic context of virulence were assessed. First, a broad-scale analysis of the tomato apoplast was undertaken, which identified metal ions, sugars, organic acids and amino acids, the most abundant of which was the non-protein amino acid gamma-aminobutyric acid (GABA). The impact these components had on the expression of virulence genes and metabolism in Pst DC3000 were then tested. Components such as fructose and aspartate caused high levels of virulence gene expression which correlated with the accumulation of intracellular glutamate, whereas repressive components, such as GABA and threonine, resulted in lower glutamate levels. Second, metabolic flux analysis showed that Pst DC3000 underwent major changes in central carbon metabolism in response to virulence gene inducing conditions. The identification of altered internal metabolism in Pst DC3000 cells expressing virulence genes led to the conclusion that Pst DC3000 may understand its external environment by sensing intracellular metabolites or metabolic fluxes. Third, the role of GABA assimilation in virulence was explored, and it was found that high internal GABA levels resulted in virulence gene repression. In addition, previously unidentified mechanisms for GABA uptake and transport were detected by the use of a novel ‘unlabelling’ experiment.

Pseudomonas syringae produz núcleos de gelo biológicos de grande eficiência. Bioaerossóis destas células tem potencial de participar na glaciação de nuvens, podendo influenciar a precipitação. Foram estudadas como as condições as quais P. syringae está sujeita em suspensão na atmosfera afetam sua sobrevivência e sua atividade de nucleação de gelo. Duas cepas foram testadas, e ambas apresentaram baixa tolerância ao UV-C e ao UV-B, mas exibiram uma maior resistência quando expostas a um espectro semelhante ao encontrado no ambiente. A atividade de congelamento de uma das cepas (pv. syringae) não foi afetada pelo UV, enquanto que para a outra (pv. garcae) houve uma redução moderada. Em resposta à dessecação, pv. garcae foi substancialmente mais resistente que pv. syringae. Isto também afetou a nucleação de gelo das cepas. Em ensaios adicionais, estas bactérias foram expostas em um voo de balão estratosférico, e a uma simulação em laboratório das condições no topo da troposfera. Nestes dois experimentos, sobreviventes protegidos do UV foram recuperados.
Pseudomonas syringae produces biological ice nuclei of great efficiency. Bioaerosols of these cells have the potential to take part in cloud glaciation, possibly influencing the precipitation. It was studied how the conditions to which P. syringae is subjected while in suspension in the atmosphere affect its survival and its ice nucleation activity. Two strains were tested, and both showed a low tolerance to UV-C and UV-B, but exhibited a higher resistance when exposed to a spectrum similar to the one found in the environment. The freezing activity of one of the strains (pv. syringae) was not affected by the UV, while that for the other (pv. garcae) there was a moderate reduction. In response to desiccation, pv. garcae was substantially more resistant than pv. syringae. This also affected the ice nucleation by the strains. In additional assays, these bacteria were exposed in a stratospheric balloon flight, and to a laboratory simulation of the conditions at the top of the troposphere. After these two experiments, survivors protected from the UV were recovered.

Pseudomonas syringae is an important bacterial plant pathogen that, as a species, is known to cause disease on hundreds of different plant species. However, any individual pathovar of P. syringae typically only causes disease on one or a few plant species, which constitute the host range of the pathovar. Plants are generally resistant to most pathogens primarily because the plant innate immune system is capable of recognizing conserved microbial-associated molecular patterns (MAMPs). Adapted pathovars of P. syringae secrete effector proteins through a Type Three Secretion System (T3SS) to suppress the immune response elicited by their MAMPs. However, secretion of effectors can also trigger a strong plant immune response if the plant harbors resistance proteins capable of recognizing the secreted effectors. Successful pathovars, therefore, must secrete a combination of effectors capable of suppressing MAMP/Pattern-Triggered Immunity (PTI) without eliciting Effector-Triggered Immunity. Here we identify several novel strategies employed by P. syringae to overcome the plant immune system and cause disease. First, we demonstrate that, in place of the canonical T3SS used by all known pathogens of P. syringae, several apparently nonpathogenic isolates of P. syringae employ a novel T3SS that is functional but not necessary for colonization of plants. Despite being closely related to pathogenic isolates of P. syringae, the isolates employing the noncanonical T3SS do not cause disease on any tested plants and instead appear to act more as commensal organisms. Second, we advance the understanding of PTI by identifying a second region of bacterial flagellin that triggers PTI in addition to the archetypical MAMP flg22, which is recognized by the archetypical plant receptor FLS2. This new elicitor, termed flgII-28, is also detected by FLS2 and appears to be under selection in very closely related lineages of P. syringae. Alleles of flagellin present in one recently expanded and agriculturally problematic lineage of P. syringae appear to trigger less PTI on their host plant, tomato, than the ancestral allele suggesting that avoidance of PTI through allelic diversity in MAMPs is an effective alternative strategy to suppression of PTI through delivery of effectors. Finally, we start to elucidate a role for chemotaxis (chemical-directed movement) in P. syringae pathogenicity. Not only is chemotaxis required for pathogenicity of P. syringae on plants, but it also appears to contribute to delimiting the host range of several P. syringae pathovars. These results highlight that additional aspects of P. syringae pathogenicity, such as chemotaxis, can directly contribute to defining the host range of individual P. syringae pathovars. The current paradigm of P. syringae pathogenicity posits that MAMPS and the repertoire of effector proteins are the primary determinant of the host range of any P. syringae pathovar; in contrast these results inspire a more nuanced view of pathogenicity that considers multiple aspects of the infection process.
Ph. D.

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2009.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 28).
Endotracheal tube insertion requires the measurement of very low pressure. Currently, there exists no reliable method or device that is integral with the inflation syringe for measuring this pressure. Thus, a device for quickly and easily reading the pressure was created within the syringe currently used to pressurize the tube. This device takes the form of elastomeric bellows. These bellows were analyzed to determine the optimum geometry for the pressures involved in the procedure. Although no closed-form model exists for this analysis, FEA was used to obtain accurate results. Using the optimized bellows, a complete for-manufacturing design was created. This design concept has received much acclaim from the medical community and has great promise in transforming many medical procedures which require such measurement..
by Samuel C. Duffley.
S.B.

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.
Includes bibliographical references (leaf [54]).
Optimization of the current labor resources at a Singapore pharmaceutical company is necessary to control the labor cost effectively without affecting the production capacity. Two new labor allocations were proposed. They featured higher labor flexibility to reduce the response time to machines failures, as well as more focused job scope to reduce work interruptions. The labor tasks were also categorized based on skill levels to facilitate the implementation of skill-based pay system in order to motivate employees. Computer simulation was used to study the performance of the new labor allocation proposals. While Proposal 1 had a lower productivity than the current labor allocation, proposal 2 showed an increase as compared to current labor allocation. The financial analysis predicted a total annual benefit of S$320,246 in the form of labor cost reduction and increased productivity from the implementation of proposal 2 with the current number of production technicians. Keywords: Labor Allocation, computer simulation, optimization The content of the thesis is modified to protect the identity of the attachment company. The name of the company and confidential information are omitted.
by Sze Sen Liaw.
M.Eng.

3D printers require a reliable and robust control system to provide the proper quality for printed parts. Dispenser 3D printers are widely used in various fields of scientific research. The goal of this project is to build a disperser 3D printer based on Printrbot 3D printer, design and implement the control system and software. This system was able to control the dispenser, performed the correct operation according to the instructions. The operating system was built by LabVIEW for file reading and printer control.

The aim of this thesis is to describe the users visiting the syringe exchange clinic in Malmö with respect to what characterises the group, how they utilize the services of the clinic and how their patterns of participation relate to risk behaviour, physical and mental health and social development. The heterogeneity of the group has been captured by the use of Stimsons dimensions “integration in majority society” and “involvement in sub-culture”, yielding four different groups of syringe exchangers: “stables”, “loners”, “two-worlders” and “junkies”. The study rests on two sources of data: a register from the clinic including all syringe exchangers that have visited the clinic between 1989 and 2003, altogether 3660 individuals, and an interview of visitors at the clinic during 1995, including 496 persons. The results show that syringe exchangers, compared to other persons with severe addiction in Malmö, to a larger extent use amphetamine as their drug-of-choice, are older and inject more irregularly. The population visiting the clinic is heterogeneous with respect to integration in society and involvement in sub-cultures. The group classified as junkies do, as expected, display the highest inclination to share syringes and needles with other and hence have the most advanced risk behaviours. As to utilization of the programme, the results show that the longer the syringe exchangers stay in the programme, the more frequent they visit it. Also with respect to utilization-patterns, we find substantial variations within the studied group. Five categories are discernible: drop-in visitors with only one or two visits, sporadic visitors who in spite of contacts over a number of years never really establish a regular contact, intermittent visitors who have had contact over several years but display a very irregular visiting pattern, regular visitors who relatively fast establish a consistent contact with visits between uniform time intervals and frequent visitors who tend to stay longer than others and visit the clinic more often. Another aspect of utilization is to what extent the distribution of needles and syringes cover the needs of the visitors. With a strict definition of need, only a minority manages to cover their needs, but if we accept a more extensive individual re-use, around 90 percent of the average need is covered. Data also reveals that a very high proportion of the users on at least one occasion have visited the programme without syringe exchange taking place or any complementary service delivered. Basically these visits seem to be of a more social nature, reinforcing the contacts between the staff and the visitors. Data do not give any clear support for the basic assumption that syringe exchange reduce the incidence of HIV or hepatitis. Recent sharing of utensils or low coverage of syringe need through the programme do not predict a higher infection risk. Instead we find that the social contacts with the staff (without syringe exchange) function as a predictor of lower incidence. This indicates that the mechanisms may be more complex than just related to the provision of clean needles and syringes. The result shows that integration increase over time while sub-cultural involvement decreases. However, the patterns for different groups are very diverse and we find no evidence that more frequent contacts as such are related to increased integration. There is however, some evidence that social visits are positively related to increased integration. No support could be found for the assumption that the programme increases the number of severe addicts.

Le dessechement bacterien du poirier du a p. S. Pv. Syringae est frequemment observe dans les principales zones productrices de poires. Bien que n'entrainant qu'exceptionnellement la mort de son hote, cette bacterie, de type necrogene, est neanmoins responsable de nombreuses lesions necrotiques sur feuilles, fleurs et fruits ainsi que de chancres sur rameaux. Deux caracteristiques essentielles de p. S. Pv. Syringae ont ete analysees: le pouvoir pathogene et la capacite epiphyte. Bien que considere comme pouvant infecter une large gamme d'hotes, le pv. Syringae a montre une specificite au niveau de son pouvoir pathogene: seules les souches isolees de poirier peuvent induire des symptomes sur cet hote. L'etude en conditions controlees du comportement epiphyte de souches pathogenes et non pathogenes a souligne l'importance du facteur humidite dans la survie epiphyte de p. S. Pv. Syringae; la faculte de survie sous des conditions defavorables apparait plus marquee pour les souches pathogenes que pour les souches non pathogenes. L'etude de l'interaction entre les deux caracteres epiphyte et pathogene d'une souche de p. S. Pv. Syringae isolee du poirier a ete entreprise par le biais d'une mutagenese aleatoire a l'aide du transposon tn5. A l'issue de cette mutagenese, 60 mutants presentant un pouvoir pathogene altere ont ete selectionnes. L'etude de l'aptitude epiphyte de quelques mutants non pathogenes caracterises par des phenotypes differents: agress#-, dsp#-, hrp#- et tox#-, a montre que quel que soit le phenotype des mutants, l'alteration du pouvoir pathogene entraine systematiquement une alteration de l'aptitude epiphyte. Cette etude a donc permis de montrer qu'il existe une relation etroite entre le pouvoir pathogene et l'aptitude epiphyte de p. S. Pv. Syringae sur le poirier