Environmental Changes in Eastern Lapland during the last 50 years

The study is sought to study how and if the environment has changed in eastern Finnish Lapland in a long-term perspective. Variables related to the current state of the environment, are atmospheric composition and aerosols, meteorology, and biology. The study is based on measurements from Värriö Subarctic Research station for the years 1973 to 2021. Included in atmospheric composition, are the atmospheric anthropogenic gas concentrations of CO, NOx, O3 and SO2. SO2 is also used in a proxy to estimate H2SO4 concentrations. Decreasing long-term trends are found for CO, NOx, SO2 and H2SO4. The decreasing emissions from Kola peninsula, is the cause for long-term decrease of SO2, which result in decreasing H2SO4 concentrations. Results of particle size distribution show an increasing concentration of small particles and decrease of large particles. Decline of particles leads to less NPF, CCN and will resultingly influence cloud properties. Air temperature has increased 2.38 °C and snow cover days have decreased by three weeks, between 1975 and 2021. Snow depth and precipitation show less significant changes. Heat sum have from 1981 to 2021 increased with 247 °C days, indicating more active and growing trees. Birch leave development show indications of leave burst and developed leaves to occur at earlier date, over the years 1981-2021. Grouses, shorebirds, and cavity-nesters show large inter-annual variations. Some of the bird species appears to benefit from environmental changes while others appear to have difficulty adapting

Utviklingen på Frans Josefs land. Konsekvenser for norsk sikkerhetspolitikk

Frans Josefs land har gjennom mange år hatt en viktig rolle i sovjetisk historie knyttet til nasjonal sikkerhet. Etter at Putin kom til makten ved århundreskiftet, ble øygruppen på nytt aktuell. Oppbyggingen av ny og moderne militær infrastruktur og utstasjonering av væpnede styrker har gjort Frans Josefs land til en egnet plattform til å underbygge russiske ambisjoner både i Arktis og globalt. For å få en forståelse av hva utviklingen på Frans Josefs land betyr for norsk sikkerhetspolitikk, har oppgaven analysert utviklingen på øygruppen fra århundreskiftet og frem til i dag. Elementene i analysen består av russisk politikk for Arktis, tilgjengeliggjort gjennom russiske offisielle dokumenter, og den faktiske utviklingen på Frans Josefs land, etablert primært gjennom pressemeldinger, nyhetsartikler og forskningslitteratur. Funnene i oppgaven peker på at utviklingen på Frans Josefs land er et resultat av langsiktig planlegging. Men utviklingen har tatt lang tid, og det er fortsatt svakheter i reelle kapasiteter og evnen til å understøtte disse, som svekker synet på hva Russland egentlig har oppnådd med oppbyggingen. På den andre siden har oppbyggingen vist seg å ha hatt stor symboleffekt. Denne effekten har vært med på å skape usikkerhet rundt russiske intensjoner i Arktis, og er en mulig grunn for den økte aktiviteten i norske nærområder, fra både alliert og russisk hold. Oppgaven belyser utviklingen på Frans Josefs land og bidrar til å gi et mer nyansert bilde av det som faktisk ligger til grunn, for det som må sies å være sukksesfull russisk avskrekking

Pharmaceutical product modularization as a mass customization strategy to increase patient benefit cost-efficiently

Customized pharmaceutical products aim to comply with the individual needs of a patient to enhance the treatment outcome. The current pharmaceutical production paradigm is, however, dominated by mass production, where the pharmaceutical products embrace a one-size-fits-all design with a low possibility of treatment optimization to patient needs. This production paradigm is not designed or intended for customized pharmaceutical products and operating this production context for customized pharmaceutical products is argued to be cost-inefficient. To address this challenge of inefficient production of customized pharmaceutical products, this study proposes an approach to modular pharmaceutical product design. As a mass customization strategy, product modularization enables serving customers with customized products cost-efficiently. The proposed modular pharmaceutical products integrate three product design requirements originating from patient needs: a scalable dose strength, a flexible target release profile, and a scalable treatment size. An approach to assess the value of these product designs is presented, by means of proposing three benefit metrics complying with respective design requirements and a cost metric assessing the cost of producing these modular pharmaceutical product designs. Results suggest that pharmaceutical product modularization can, by keeping the number of produced components low, substantially increase the external product variety and, hence, enhance the treatment outcome of patients. Fur-thermore, results indicate that the achieved benefit for the patient through product modularization increases beyond additional costs arising during production. However, a careful modularization must be performed to optimize the tradeoff between the increased benefit and cost

High Content Solid Dispersions for Dose Window Extension: A Basis for Design Flexibility in Fused Deposition Modelling

Purpose: This study uses high drug content solid dispersions for dose window extension beyond current demonstrations using fused deposition modelling (FDM) to; i) accommodate pharmaceutically relevant doses of drugs of varying potencies at acceptable dosage form sizes and ii) enable enhanced dose flexibility via modular dosage form design concepts. Methods: FDM was used to generate ~0.5\ua0mm thick discs of varying diameter (2–10\ua0mm) from melt-extruded feedstocks based on 10% to 50% w/w felodipine in ethyl cellulose. Drug content was determined by UV spectroscopy and dispensing precision from printed disc mass. Results: Mean felodipine content was within \ub15% of target values for all print volumes and compositions including contents as high as ~50% w/w. However, poor dispensing precision was evident at all print volumes. Conclusions: In pursuit of dose flexibility, this successful demonstration of dose window extension using high content solid dispersions preserves FDM design flexibility by maintaining applicability to drugs of varying potencies. The achieved uniformity of content supports the application of varying content solid dispersions to modular dosage form concepts to enhance dose flexibility. However, poor dispensing precision impedes its utilisation until appropriate compatibility between FDM hardware and materials at varying drug contents can be attained

Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets

Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to establish non-destructive, fast, and compact techniques to assess porosity, in-situ, during the manufacturing process. In this paper, the terahertz frequency-domain (THz-FD) technique was explored as a fast, non-destructive, and sensitive technique for porosity measurement of pharmaceutical tablets. We studied a sample set of 69 tablets with different design factors, such as particle size of the active pharmaceutical ingredient (API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and compaction force. The signal transmitted through each tablet was measured across the frequency range 500-750 GHz using a vector network analyzer combined with a quasi-optical set-up consisting of four off-axis parabolic mirrors to guide and focus the beam. We first extracted the effective refractive index of each tablet from the measured complex transmission coefficients and then translated it to porosity, using an empirical linear relation between effective refractive index and tablet density. The results show that the THz-FD technique was highly sensitive to the variations of the design factors, showing that filler particle size and compaction force had a significant impact on the effective refractive index of the tablets and, consequently, porosity. Moreover, the fragmentation behavior of particles was observed by THz porosity measurements and was verified with scanning electron microscopy of the cross-section of tablets. In conclusion, the THz-FD technique, based on electronic solutions, allows for fast, sensitive, and non-destructive porosity measurement that opens for compact instrument systems capable of in-situ sensing in tablet manufacturing

Terahertz Frequency-Domain Sensing Combined with Quantitative Multivariate Analysis for Pharmaceutical Tablet Inspection

Near infrared (NIR) and Raman spectroscopy combined with multivariate analysis are established techniques for the identification and quantification of chemical properties of pharmaceutical tablets like the concentration of active pharmaceutical ingredients (API). However, these techniques suffer from a high sensitivity to particle size variations and are not ideal for the characterization of physical properties of tablets such as tablet density. In this work, we have explored the feasibility of terahertz frequency-domain spectroscopy, with the advantage of low scattering effects, combined with multivariate analysis to quantify API concentration and tablet density. We studied 33 tablets, consisting of Ibuprofen, Mannitol, and a lubricant with API concentration and filler particle size as the design factors. The terahertz signal was measured in transmission mode across the frequency range 750 GHz to 1.5 THz using a vector network analyzer, frequency extenders, horn antennas, and four off-axis parabolic mirrors. The attenuation spectral data were pre-processed and orthogonal partial least square (OPLS) regression was applied to the spectral data to obtain quantitative prediction models for API concentration and tablet density. The performance of the models was assessed using test sets. While a fair model was obtained for API concentration, a high-quality model was demonstrated for tablet density. The coefficient of determination for the calibration set was 0.97 for tablet density and 0.98 for API concentration, while the relative prediction errors for the test set were 0.7% and 6%for tablet density and API concentration models, respectively

Adapting discrete goods supply chains to support mass customisation of pharmaceutical products

Emerging research within the field of personalised medicines has aimed to enhance patient treatment through the use of pharmaceutical products that are customized to the individual needs and preferences of the patient. The currently dominant production platforms of pharmaceutical products, however, regard a mass production paradigm and are thus unfeasible for the production and provision of personalised medicines. The production platforms are not designed or are intended for a customisation context. Operating such a context with the current supply chain entails challenges such as increasing costs, time to patient and efforts in quality assurance activities. To address these challenges, this paper presents four reconfigured pharmaceutical supply chain designs. A qualitative operational performance assessment elicits the strengths and weaknesses of the respective supply chain design operating in a customisation context. The results suggest that a later point of variegation, i.e., the point in the supply chain where the final customisation is achieved, can relieve the operational effort of the stakeholders in the supply chain while providing the benefits of personalised medicines, i.e., an enhanced treatment outcome of the patient. A trade-off remains, however, between the supply chain’s decreased operational effort and degree of necessary reconfigurations, such as introducing new functions to stakeholder operation, reallocating activities to other stakeholders or educating stakeholders

Enabling modular dosage form concepts for individualized multidrug therapy: Expanding the design window for poorly water-soluble drugs

Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and technically explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clinical dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision (<5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% w/w and 50% w/w drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy

High sensitivity gas spectroscopy of porous, highly scattering solids

We present minimalistic and cost-efficient instrumentation employing tunable diode laser gas spectroscopy for the characterization of porous and highly scattering solids. The sensitivity reaches 3 x 10(-6) (absorption fraction), and the improvement with respect to previous work in this field is a factor of 10. We also provide the first characterization of the interference phenomenon encountered in high-resolution spectroscopy of turbid samples. Revealing that severe optical interference originates from the samples, we discuss important implications for system design. In addition, we introduce tracking coils and sample rotation as new and efficient tools for interference suppression. The great value of the approach is illustrated in an application addressing structural properties of pharmaceutical materials