Mediterranean Vector of International Relations in the Mirror of Sigismund of Luxembourg’s Conflict with Venice (1411—1413)

The article covers international and diplomatic aspects of the conflict of Sigismund of Luxembourg, the King of Hungary and the Romans, and the Republic of Venice in 1411—1413. Venetian claims to Dalmatia that nominally belonged to the Hungarian Crown were the formal reason of the conflict. The article notices that the main battleground was in Italia, not Dalmatia. The author thereupon concludes that the actual factor of the events was the competition between Italian states. But contrary to the traditional opinion the researcher assigns the part of the main power that competed with Venice to Florence, not Genoa. In the early fifteenth century it entered into the struggle for the outlet to the sea and sought the extension of its influence for account of new trade lines that connected the Mediterranean with Central and North Europe. Meanwhile, the head-on clash of the republics was ruled out because their relations guaranteed them both the safety of the political balance of Italy and the defence of the peninsula from external actions. But Florence could force Venice by the manipulation by the Italian policy of the King Sigismund. The instrument of the pressure was the potential union of the King and the Pope John XXIII. It was the interests of Florence that made it possible to explain the reason that kept them from direct official contacts. The investigation of the nature of the conflict reveals also its indirect connection with historical events related to West European states, Poland, the Teutonic Order, the Byzantine Empire, the Ottomans and the Golden Horde.

Calibration of reliability-based safety factors for sand boiling in excavations

This study calibrated the required factors of safety of five analysis methods for sand boiling using reliability theory. The factors of safety computed by the five analysis methods were compared with the results of a series of sand boiling model tests. The comparison shows that rigorous methods (Terzaghi’s and Harza’s methods) were more accurate in predicting the factors of safety compared to the simplified methods (Harr’s, simplified Terzaghi’s, and simplified Harza’s methods). The statistics of the model factor for each method, defined as the actual factor of safety divided by the computed one, was calibrated by the model test results. These statistics were then used to establish the relationship between the target probability of failure and the required factor of safety by reliability theory. Verification using a full-scale sand boiling case history shows that the required factor of safety calibrated by the reliability theory was more reasonable than the required factors of safety in references and design codes.

Analysis of the Blasting Effect on the Environment around Blasting Areas at Pt. Semen Baturaja Persero, Tbk.

Semen Baturaja Persero, Tbk is one of the companies engaged in the production of cement that takes raw materials through limestone mining process located in Baturaja City, OKU Regency, South Sumatera Province. Limestone mining activities use blasting activity that produces blasting effects and flyrock. Measurements of vibration and flyrock frequencies obtained a maximum value for vibration of 4.66 mm/s and predicted farthest distance of flyrock above 170 m when powder factor exceeds 0.1 kg/m3. The results of the data show that the level of emission has exceeded the standard limits for second class buildings (3 mm/s) based on (SNI) 7571: 2010. Blasting just 175-300 m from the nearest settlement and already exceed the save distance for equipment 300m and 500m for human activity based on USBM (United States Bureau of Mines). To reduce the vibration level, the maximum number of mass per delay is 43 kg/delay with PPV parameter 3 mm/s at 170m distance. Actual factor powder should not exceed 0.1 kg / m3 to minimize flyovers in safe zones not exceeding 150 m.

Expectations and Concerns Towards New Extended Half-Life (EHL) Products - Results of Surveys Among Haemophilia Patients from the Dach Region

Background: In Western Europe most patients with haemophilia (PWH) have the opportunity to get regular prophylaxis and can life normal lives due to the availability and funding of factor concentrates. The majority of haemophilia patients have to inject themselves every other day or three times a week.The need of frequent injections may impact negatively patients' treatment adherence which might result in increased annual bleeding rate and impaired quality of life. Therefore there is a need for half-life extended (EHL) products which will be launched in the next years in Europe for treatment of haemophilia A and B and are expected to improve patients' quality of life. However, little is known about patients' perspectives on the use of these new EHL products and their willingness to switch to these products. Aim: National Member Organisations (NMO) of haemophilia patients from the DACH Region (D=Germany, A=Austria, CH=Switzerland) were interested to better understand PWH's expectations and concerns towards these new EHL products in order to adapt haemophilia treatment to real patients' needs. Methods: A systematic postal survey was sent out to 2,644 patients and parents of children with haemophilia A or B in Germany (2015), Switzerland (2016) and Austria (2016). The postal survey included questions concerning demographic and clinical data of the patient, knowledge about half-life of actual factor concentrates (FC) and attitudes towards FC in terms of satisfaction with actual factor concentrate, expectation towards new EHL products, willingness to switch to new EHL products, required information for decision making, preferred information sources and facilitation of therapy in general. Results: In total 1,013 questionnaires were sent back (38.3%); 2 patients had to be excluded from further analysis since these patients had VWD. 747 adult haemophilia patients and 262 parents of haemophilic children participated, 2 respondents could not be classified. The majority of patients had haemophilia A (84.1%), were severely affected (73%), received prophylaxis (56.6%), mostly three times a week (40.9%) and used recombinant products (59.4%). 14% had a history of an inhibitor (past, actual). Most of the patients and parents did not know the correct half-life of the actual FC [FVIII: 30%, FIX: 75%]. In general they were satisfied (M=4.4±0.8) with their actual FC; only 4.1% were unsatisfied, mainly with difficult manageability and short half-life of FC. They expected from the new products to provide less frequent injections, better efficacy and safety/no side effects. 59.6% would be willing to switch to new products if they have a prolonged half-life and have the same safety of the actual FC. Reasons for not willing to switch were fear of inhibitor development and no side effects of actual FC. They had almost no information about the new up-coming products, wish more information about half-life, possible side-effects and efficacy and would consider changing product if the prolongation of the half-life is at least double as high as the actual FC. 20.6% would switch already with a half-life prolongation of 1.2-1.5 times longer; 3.3% would not switch at all. The majority wanted to receive information about new products from their haemophilia treater (77.1%), newsletter of their NMO (73.4%) and information letter from their HTC/NMO (35.7%). They would wish smaller packages, different mode of administration and better manageability of the product in order to facilitate their therapy. There was a significant difference across countries regarding treatment regimen (p<.0001) and used product category (p<.0001); in Germany more patients were on prophylaxis (71.3%) and in Switzerland more patients used recombinant products (75.8%). No differences were found for the satisfaction with their actual product, their willingness to switch to new EHL products in general and the time of required half-life prolongation. In Switzerland more patients required information on costs of the new EHL products for an adequate decision making process for switching (p<.0001). Conclusions: In this representative survey among patients and parents of children with haemophilia of the DACH Region it could be shown that even though they were generally satisfied with their actual FC the majority would be willing to switch from their actual FC to the new up-coming EHL products assuming the half-life is prolonged and has the same safety of the actual FC. Disclosures von Mackensen: Shire: Research Funding; SOBI: Research Funding. Kalnins:SOBI: Research Funding. Lino:SOBI: Research Funding. Joerg:SOBI: Research Funding. Albisetti:Boehringer Ingelheim: Other: Pediatric Expert Working Group. Weiss:Shire: Research Funding.

Perception of Actual Factor Concentrates and Expectations Towards Future Treatment with New Long-Lasting Products - Results of a Survey Among Haemophilia Patients in Germany - Analysis of Open Questions

Background: Prophylactic treatment allows patients with haemophilia (PWH) to live an approximately normal life. The majority of German PWH receive prophylaxis. The need of frequent weekly injections may impact negatively treatment adherence. This is the expected reason which might result in increased annual bleeding rate. Therefore there is a need for half-life extended products which will be launched end of this year in Germany. However, little is known about patients' perspectives on the use of new products with extended half-life and their willingness to switch to these products. Aim: The German patient organisation DHG is interested to better understand PWH's expectations and concerns towards these new products in order to adapt their support for the haemophilia community. Methods: The study consisted of two phases: 1) conduct of separate focus groups with adult haemophilia patients and parents of haemophilic children with respect to the new long-lasting products across Germany; 2) based on the focus group results construction of a questionnaire for a systematic postal survey among DHG members with haemophilia A or B (n=1,499). Results: The postal survey included questions concerning haemophilia, knowledge about half-life of actual factor concentrates (FC) and attitudes towards actual FC and open ended questions concerning the expectations towards new products and how therapy could be facilitated. The open ended questions should give the participants the chance to write down other aspects, problems, laments and other wishes. Several aspects could be mentioned by the same subject. Out of the sent 1,499 questionnaires 697 questionnaires were sent back; mainly from adult patients (n=518), 177 from parents of haemophilic children. Patients had haemophilia A (83.7%), in a severe form (77.8%), were on prophylaxis (61.4%), mostly three times a week (47.8%) and used recombinant products (57.8%). 14.1% have had an inhibitor. Open questions were answered by 462 respondents, at least 1 to maximum 5 aspects were mentioned. Open questions on the current situation ["facilitation of therapy"] (n=302): less packaging waste (n=129), no cooling required (n=61), sc injections/oral medication/nasal medication (n=54), better supplies like perfect injection needle etc. (n=27), prefilled syringe (n=25), diversity of package size (125 iU to 4000 iU) (n=24), support in home care therapy (n=17), simpler treatment documentation (n=9), improved logistic/delivery for home treatment (n=8). Open questions for future situation (n=160) ["expectations towards new long-lasting products"]: less injections (n=492), same safety/efficacy/compatibility (n=44), better quality of life (n=22), no fridge (n=16), treatment costs/reduction-no increase (n=15), higher trough level (n=9), smaller packaging (n=8), easier handling (n=8), and many more mentioned 1- 3 times. Conclusions: The answers to the open questions in this representative survey among German haemophilia patients and parents of children with haemophilia provide important additional information and insights in the unmet needs of haemophilia patients, which will help the German patient association and pharmaceutical companies to better inform patients about the new up-coming products taking patients needs into consideration. Disclosures Kalnins: SOBI: Consultancy. Miesbach:SOBI: Consultancy. von Mackensen:SOBI: Consultancy.

Perception of Actual Factor Concentrates and Expectations Towards Future Treatment with New Long-Lasting Products - Results of a Survey Among Haemophilia Patients in Germany

Background: Prophylactic treatment allows patients with haemophilia (PWH) to live a normal life, however the need of frequent weekly injections may impact negatively treatment adherence which might result in increased annual bleeding rate and impaired quality of life. Therefore there is a need for half-life extended products which will be launched in the next years. However, little is known about patients' perspectives on the use of new products with extended half-life and their willingness to switch to these products. Aim: The German patient organisation DHG is interested to better understand PWH's expectations and concerns towards these new products in order to adapt their support for the haemophilia community. Methods: The study consisted of two phases: 1) conduct of separate focus groups with adult haemophilia patients and parents of haemophilic children with respect to the new long-lasting products across Germany; 2) based on the focus group results construction of a questionnaire for a systematic postal survey among DHG members with haemophilia A or B (n=1,499). Results: The postal survey included questions concerning haemophilia, knowledge about half-life of factor concentrates and attitudes towards factor concentrates (FC). In total 697 questionnaires were sent back (46.5%); 518 patients and 177 parents of haemophilic children. The majority of patients had haemophilia A (83.7%), were severely affected (77.8%), received prophylaxis (61.4%), mostly three times a week (47.8%) and used recombinant products (57.8%). 14.1% had a history of an inhibitor. Most of the patients and parents did not know the correct half-life of the actual FC [FVIII: 30.1%, FIX: 74.5%]. In general they were satisfied (M=4.4±0.8) with their actual FC; only 4.1% were unsatisfied, mainly with short half-life, difficult manageability and need to store it in the fridge. They expected from the new products to have prolonged half-life, better stability, better transparency concerning production of the FC and improved manageability. 59% would be willing to switch to new products if they have a prolonged half-life, provide more security when travelling and have the same safety of the actual FC. Reasons for not willing to switch were fear of inhibitors and uncertain safety of new product as well as satisfaction and no side effects of actual FC. They have almost no information about the new up-coming products, wish more information about half-life, possible side-effects and efficacy and would consider changing product if the prolongation of the half-life is at least double as high as the actual FC. The majority wants to receive information about new products from their haemophilia treater (79%), leaflets/newsletter of DHG (77%) and information letter from HTC/DHG (32%). Analyses between clinical subgroups showed significant differences for knowledge of half-life of FVIII for type of haemophilia (p<.0001), severity (p<.0001), treatment (p<.0001) and age (p<.031). Significantly more patients on prophylaxis would be willing to switch to new products because of their prolonged half-life (92%; p<.0001) and benefits for doing sports (53%, p<.0001), while on-demand patients would do so because of their longer stability outside the fridge (69%; p<.0001), advantages for surgeries (68%; p<.0001), easier application (44%; p<.001) and 24% would be motivated to switch to prophylaxis. No differences were found for satisfaction with actual FC and the willingness to switch to new products. Presence of inhibitors did not have an impact. In the five focus groups 23 adult haemophilia patients (78.3% HA; 78.3% severely affected) and 9 parents of haemophilic children (88.9% HA; 77.8% severely affected) were interviewed (Hamburg, Cologne, Munich, 2x Dresden). Conclusions: In this representative survey among German patients and parents of children with haemophilia they reported to be satisfied with their actual FC. Nevertheless, unsatisfactory aspects of their actual FC are half-life, manageability and storage conditions. The majority did not have a lot of information of the new long-lasting products, but would be willing to switch from the actual FC to these products assuming the half-life is prolonged and has the same safety of the actual FC. These findings will help patient associations and pharmaceutical companies to better inform patients about the new up-coming products taking patients needs into consideration. Disclosures von Mackensen: SOBI: Consultancy. Heinrich:SOBI: Consultancy. Kalnins:SOBI: Consultancy. Oldenburg:SOBI: Consultancy.

U.S. Aggregate Agricultural Production Elasticities Estimated by an Arima Factor Share Adjustment Model

In an effort to circumvent the multicollinearity problems associated with direct estimation of the aggregate agricultural production function, many economists have used indirect estimation procedures. Because in equilibrium the partial production elasticities of an industry composed of perfectly competitive firms are equal to their respective factor shares, the latter have been used as a means of estimating production elasticities. Most researchers have simply assumed that actual factor shares are equilibrium values (e.g., Griliches; Rosine and Helmberger). Substantive contributions recently have been made in explaining the process of factor share adjustment by changes in prices and technology over time (Binswanger; Lianos). However, except for the work nearly 15 years ago by Tyner and Tweeten (1965), agricultural economics literature is largely silent on the measurement of differences between actual and equilibrium factor shares. It is this issue with which we are primarily concerned in this article. Therefore, our point of departure is the work by Tyner and Tweeten.