Stenmjöl eller naturgrus i betong : En jämförande studie

  The objective of this thesis is to examine the difference in workability in fresh concrete, when crushed fine aggregate replaces natural gravel. The shape of the fine aggregate,  packing and flow of six crushed material and three natural materials will be determined by easy studies, the results will be compared with a slump cone test

Användning av den mobila tjänsten SMS i ett system

Syftet med uppsatsen var att undersöka vad som gör att en användare vill använda SMS i en organisation och vilka faktorer som påverkar användandet av detta system, det vill säga acceptansen av att använda det. Då denna typ av system är relativt nya tyckte vi att detta var ett intressant ämne att undersöka, samtidigt som vi ville se vilka faktorer som påverkar användaren i avseende till användning av ett specifikt SMS-baserat system. Det kan även vara intressant för företag som vill implementera eller utveckla den här typen av system. Utifrån syftet bestämde vi oss för ett visst tillvägagångssätt som vi skulle använda oss av för att kunna få svar på våra frågor. Tillvägagångssättet var att leta i den litteratur vi haft på tidigare kurser inom det systemvetenskapliga programmet för att hitta en teori som kunde ge oss stöd för ett resonemang. Vår tanke var sedan att hitta en organisation som använder sig av ett SMS-baserat system för att sedan analysera vilka faktorer som påverkar användningen av systemet. Vi bestämde oss för att utföra en enkätundersökning, gällande vårt syfte för att kunna dra slutsatser om användandet av sådana typer av system. Resultatet visade att teknikintresset innan användning av ett SMS-baserat system visar sig ha inverkan på användningen. Supporten från organisation påverkade användningen i mycket hög utsträckning, vilket visade sig i högre grad av användning hos dem som fick support från sin organisation

Initial effects of a reimbursement restriction to improve the cost-effectiveness of antihypertensive treatment

Objective The Swedish Dental and Pharmaceutical Benefits Agency is re-assessing the value of all drugs included in the reimbursement scheme in order to make the most efficient use of resources. Their recent review of antihypertensive drugs included 46 substances with total annual sales of [euro]230 million ([euro]25/capita). This resulted in reimbursement restrictions for 26 substances, e.g. all angiotensin receptor blockers (ARBs).Methods We used the Swedish prescribed drug register to evaluate the initial effects on prescribing patterns using a before-and-after design, comparing utilization and expenditure with corresponding periods previous years.Results The proportion of the Swedish population being dispensed antihypertensive drugs increased by 0.5%-units to 16.5% in September-December 2008 compared to the same period in 2007. Patients initiated on ARBs decreased by 24%, whilst increasing for ACE inhibitors (ACEI) and calcium channel blockers, by 14% and 12%, respectively. The proportion initiated on ARBs prescribed an ACEI within 24 months prior to an ARB increased from 51% to 67%, with a substantial regional variation (extremal quotient 31; coefficient of variation 36%). The total expenditure decreased by 4.7% to [euro]73 million in September-December 2008 compared to the same period in 2007.Conclusions Reimbursement restrictions had a positive impact on enhancing the efficiency of antihypertensive prescribing. Resources released can be used to improve care in the future.Hypertension Reimbursement Angiotensin receptor blockers Guidelines Prescribing ACE inhibitors

Unmet Medical Need : An Introduction to Definitions and Stakeholder Perceptions

BACKGROUND: Despite increasing informal and formal use of unmet medical need (UMN) in drug development, regulation, and assessment, there is no insight into its definitions in use. This study aims to provide insight into the current definitions in use and to provide a starting point for a multi-stakeholder discussion on alignment. METHODS: A scoping and a gray literature review were performed to locate definitions of UMN in literature and on stakeholder websites. These definitions were categorized and then discussed among the multi-stakeholder author group via semistructured group discussions and open session workshops with a broader stakeholder audience. Issues with the formation of a common definition and mechanisms for use were discussed. RESULTS: The reviews yielded 16 definitions. Differences were evident, but all included 1 or more of the following elements: (adequacy of) available treatments (16 of 16: 100%), disease severity or burden (6 of 16: 38%), and patient population size (1 of 16: 6%). The stakeholder discussions led to a suggestion for a definition including the first 2 items and, depending on context, population size. The discussions also showed that quantification of UMN is highly dependent on the scope and the value framework in which it is used based on different stakeholder preferences and responsibilities. CONCLUSION: We encourage stakeholders that want to promote alignment on the concept of UMN to prospectively discuss the scope in which they want to apply the concept, what elements they find important for consideration in each case, and how they would measure UMN within the broader regulatory or value framework applicable

Unmet Medical Need : An Introduction to Definitions and Stakeholder Perceptions

BACKGROUND: Despite increasing informal and formal use of unmet medical need (UMN) in drug development, regulation, and assessment, there is no insight into its definitions in use. This study aims to provide insight into the current definitions in use and to provide a starting point for a multi-stakeholder discussion on alignment. METHODS: A scoping and a gray literature review were performed to locate definitions of UMN in literature and on stakeholder websites. These definitions were categorized and then discussed among the multi-stakeholder author group via semistructured group discussions and open session workshops with a broader stakeholder audience. Issues with the formation of a common definition and mechanisms for use were discussed. RESULTS: The reviews yielded 16 definitions. Differences were evident, but all included 1 or more of the following elements: (adequacy of) available treatments (16 of 16: 100%), disease severity or burden (6 of 16: 38%), and patient population size (1 of 16: 6%). The stakeholder discussions led to a suggestion for a definition including the first 2 items and, depending on context, population size. The discussions also showed that quantification of UMN is highly dependent on the scope and the value framework in which it is used based on different stakeholder preferences and responsibilities. CONCLUSION: We encourage stakeholders that want to promote alignment on the concept of UMN to prospectively discuss the scope in which they want to apply the concept, what elements they find important for consideration in each case, and how they would measure UMN within the broader regulatory or value framework applicable

Value chain for production of bio-oil from kraft lignin for use as bio-jet fuel

The LignoJet project aimed to achieve an intermediate lignin-oil product miscible with fossil feedstock and with a significantly reduced oxygen content. A technical concept for production has been studied that involves combined catalysed depolymerisation and hydrodeoxygenation, so called hydrogenolytic depolymerisation, of kraft lignin. Kraft lignin was separated through membrane ultrafiltration from softwood and eucalyptus black liquor followed by precipitation through LignoBoost technology. A difference in lignin properties was observed between ultrafiltration of softwood and eucalyptus black liquor through 15 and 150kDa ceramic membranes. Lignin-oils with similar oxygen content were produced regardless of origin and fractionation technique. A lignin-oil with favourable properties as precursor for refinery integration for jet fuel production as produced in small-scale batch experiments using nickel-based catalyst. Stable pumpable oils with melting point of less than 25-50 deg C and with 20-30% lower oxygen content and aromatic content were obtained that would be suitable as jet fuel precursors. The estimated production cost was found to be competitive with that of other liquid biofuels, while additional revenues could potentially be achieved by also producing chemical and materials from suitable fractions of the lignin-oil

Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer's Disease

Although there are a growing number of well-reported, late-stage clinical trial failures in Alzheimer's disease, the introduction of a disease-modifying therapy within the next 5 years may be anticipated. These treatments are likely to target Alzheimer's disease in the earlier disease stages, unlike drugs that are currently available that treat symptoms of moderate-to-severe dementia. Therefore, there is a need to establish a consensus on regulatory and health technology assessment requirements for Alzheimer's disease, as a new drug will need to undergo regulatory and health technology assessments before it becomes available to patients. This article reports the discussions and activities of the regulatory and health technology assessment expert advisory group of the 2-year ROADMAP (real-world outcomes across the Alzheimer's disease spectrum: a multimodal data access platform) project. The expert advisory group discussions identified a lack of consensus on validated outcomes in the earliest Alzheimer's disease stages, the need for filling gaps between outcomes used across clinical trials and real-world settings, and the role that real-world evidence might have in characterising the impact of a possible disease-modifying therapy on caregivers, resource use and long-term outcomes

Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer's Disease

Although there are a growing number of well-reported, late-stage clinical trial failures in Alzheimer's disease, the introduction of a disease-modifying therapy within the next 5 years may be anticipated. These treatments are likely to target Alzheimer's disease in the earlier disease stages, unlike drugs that are currently available that treat symptoms of moderate-to-severe dementia. Therefore, there is a need to establish a consensus on regulatory and health technology assessment requirements for Alzheimer's disease, as a new drug will need to undergo regulatory and health technology assessments before it becomes available to patients. This article reports the discussions and activities of the regulatory and health technology assessment expert advisory group of the 2-year ROADMAP (real-world outcomes across the Alzheimer's disease spectrum: a multimodal data access platform) project. The expert advisory group discussions identified a lack of consensus on validated outcomes in the earliest Alzheimer's disease stages, the need for filling gaps between outcomes used across clinical trials and real-world settings, and the role that real-world evidence might have in characterising the impact of a possible disease-modifying therapy on caregivers, resource use and long-term outcomes

TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism

Exome sequencing has recently identified mutations in the gene TANGO2 (transport and Golgi organization 2) as a cause of developmental delay associated with recurrent crises involving rhabdomyolysis, cardiac arrhythmias, and metabolic derangements. The disease is not well understood, in part as the cellular function and subcellular localization of the TANGO2 protein remain unknown. Furthermore, the clinical syndrome with its heterogeneity of symptoms, signs, and laboratory findings is still being defined. Here, we describe 11 new cases of TANGO2-related disease, confirming and further expanding the previously described clinical phenotype. Patients were homozygous or compound heterozygous for previously described exonic deletions or new frameshift, splice site, and missense mutations. All patients showed developmental delay with ataxia, dysarthria, intellectual disability, or signs of spastic diplegia. Of importance, we identify two subjects (aged 12 and 17 years) who have never experienced any overt episode of the catabolism-induced metabolic crises typical for the disease. Mitochondrial complex II activity was mildly reduced in patients investigated in association with crises but normal in other patients. In one deceased patient, post-mortem autopsy revealed heterotopic neurons in the cerebral white matter, indicating a possible role for TANGO2 in neuronal migration. Furthermore, we have addressed the subcellular localization of several alternative isoforms of TANGO2, none of which were mitochondrial but instead appeared to have a primarily cytoplasmic localization. Previously described aberrations in Golgi morphology were not observed in cultured skin fibroblasts