Investigating physical properties of solid dosage forms during pharmaceutical processing : Process analytical applications of vibrational spectroscopy

In order to improve and continuously develop the quality of pharmaceutical products, the process analytical technology (PAT) framework has been adopted by the US Food and Drug Administration. One of the aims of PAT is to identify critical process parameters and their effect on the quality of the final product. Real time analysis of the process data enables better control of the processes to obtain a high quality product. The main purpose of this work was to monitor crucial pharmaceutical unit operations (from blending to coating) and to examine the effect of processing on solid-state transformations and physical properties. The tools used were near-infrared (NIR) and Raman spectroscopy combined with multivariate data analysis, as well as X-ray powder diffraction (XRPD) and terahertz pulsed imaging (TPI). To detect process-induced transformations in active pharmaceutical ingredients (APIs), samples were taken after blending, granulation, extrusion, spheronisation, and drying. These samples were monitored by XRPD, Raman, and NIR spectroscopy showing hydrate formation in the case of theophylline and nitrofurantoin. For erythromycin dihydrate formation of the isomorphic dehydrate was critical. Thus, the main focus was on the drying process. NIR spectroscopy was applied in-line during a fluid-bed drying process. Multivariate data analysis (principal component analysis) enabled detection of the dehydrate formation at temperatures above 45°C. Furthermore, a small-scale rotating plate device was tested to provide an insight into film coating. The process was monitored using NIR spectroscopy. A calibration model, using partial least squares regression, was set up and applied to data obtained by in-line NIR measurements of a coating drum process. The predicted coating thickness agreed with the measured coating thickness. For investigating the quality of film coatings TPI was used to create a 3-D image of a coated tablet. With this technique it was possible to determine coating layer thickness, distribution, reproducibility, and uniformity. In addition, it was possible to localise defects of either the coating or the tablet. It can be concluded from this work that the applied techniques increased the understanding of physico-chemical properties of drugs and drug products during and after processing. They additionally provided useful information to improve and verify the quality of pharmaceutical dosage forms

Koko talo soi : Klemetti-Opisto suomalaisen musiikkikulttuurin kehittäjänä 1953-1968

This study aims to examine the operations and significance of the Klemetti Institute (Klemetti-Opisto) as a developer of Finnish music culture from 1953 to 1968 during the term of office of the Institute s founder and first director, Arvo Vainio. The Klemetti Institute was originally established as a choir institute, but soon expanded to offer a wide range of music courses. In addition to providing courses for choir leaders and singers, the Institute began its orchestral activities as early as the mid-1950s. Other courses included ear training seminars as well as courses for young people s music instructors and in playing the kantele (a Finnish string instrument) and solo singing. More than 20 types of courses were offered over the 16-year period. The Klemetti Institute s courses were incorporated into the folk high school courses offered by the Orivesi Institute (Oriveden Opisto) and were organised during the summer months of June and July. In addition to funding based on the Folk High School Act, financial assistance was obtained from various foundations and funds, such as the Wihuri Foundation. This study is linked to the context of historical research. I examine the Klemetti Institute s operations chronologically, classifying instruction into different course types, and analyse concert activities primarily in the section on the Institute s student union. The source material includes the Klemetti Institute archives, which consist of Arvo Vainio s correspondence, student applications, register books and cards, journals and student lists, course albums and nearly all issues of the Klemettiläinen bulletin. In addition, I have used focused interviews and essays to obtain extensive data from students and teachers. I concentrate on primary school teachers, who accounted for the majority of course participants. A total of more than 2,300 people participated in the courses, nearly half of whom took courses during at least two summers. Primary school teachers accounted for 50% to 70% of the participants in most courses and constituted an even larger share of participants in some courses, such as the music instructor course. The Klemetti Institute contributed to the expansion throughout Finland of a new ideal for choral tone. This involved delicate singing which strives for tonal purity and expressiveness. Chamber choirs had been virtually unheard of in Finland, but the Klemetti Institute Chamber Choir popularised them. Chamber choirs are characterised by an extensive singing repertoire ranging from the Middle Ages to the present. As the name suggests, chamber choirs were originally rather small mixed choirs. Delicate singing meant the avoidance of extensive vibrato techniques and strong, heavy forte sounds, which had previously been typical of Finnish choirs. Those opposing and shunning this new manner of singing called it ghost singing . The Klemetti Institute s teachers included Finland s most prominent pedagogues and artists. As the focused essays, or reminiscences as I call them, show, their significance for the students was central. I examine extensively the Klemetti Institute s enthusiastic atmosphere, which during the early years was characterised by what some writers described as a hunger for music . In addition to distributing a new tonal ideal and choir repertoire, the Klemetti Institute also distributed new methods of music education, thus affecting the music teaching of Finnish primary schools, in particular. The Orff approach, which included various instruments, became well known, although some of Orff s ideas, such as improvisation and physical exercise, were initially unfamiliar. More important than the Orff approach was the in-depth teaching at the Klemetti Institute of the Hungarian ear training method known as the Kodály method. Many course participants were among those launching specialist music classes in schools, and the method became the foundation for music teaching in many such schools. The Klemetti Institute was also a pioneer in organising orchestra camps for young people. The Klemetti Institute promoted Finnish music culture and played an important role in the continuing music education of primary school teachers. Keywords: adult education, Grundtvigian philosophy, popular enlightenment, Klemetti Institute, Kodály method, choir singing, choir conducting, music history, music education, music culture, music camp, Orff approach, Orff-Schulwerk, Orivesi Institute, instrument teaching, free popular education, communality, solo singing, voice production

Social-class inequalities in ill health - the contribution of physical workload

Tutkimuksen aiheita olivat yhteiskuntaluokkien väliset erot sairastavuudessa ja alentuneessa toimintakyvyssä, sekä fyysisen työkuormituksen ja joidenkin muiden työolojen vaikutus sairastavuuteen. Empiirisestä työstä on raportoitu myös neljässä kansainvälisissä tieteellisissä aikakauskirjoissa julkaistussa artikkelissa. Tässä julkaistu yhteenveto sisältää tulosten yhteenvedon lisäksi myös tutkimusta koskevien käsitteellisten ja teoreettisten kysymysten sekä tutkimustradition kriittisen katsauksen. Työn päätavoitteita olivat 1) tutkia fyysisesti kuormittavan työn, ja jossain määrin muiden työolojen osuutta yhteiskuntaluokkien välisiin eroihin sairaudessa ja toimintakyvyn alentuneisuudessa; 2) tutkia työn fyysisen kuormittavuuden, työhön liittyvien vaikutusmahdollisuuksien ja hallinnan (decision latitude), luokka-aseman, iän ja sukupuolen yhteisvaikutuksia heikentyneeseen terveydentilaan; sekä 3) tutkia missä määrin mekaanisten työaltisteiden ja tuki- ja liikuntaelinsairastavuuden välinen yhteys voi selittää yhteiskuntaluokkien välisiä eroja heikentyneessä yleisessä terveydentilassa. Tutkittavat olivat keski-ikäisiä Helsingin kaupungin työntekijöitä. Analyysit perustuivat poikittaisasetelmaan, ja käytetty aineisto oli Helsinki Health Studyn vuosien 2000 ja 2002 välillä kerättyä aineistoa. Analyyseihin käytetyssä aineistossa oli 3740:stä 8002:een tutkittavaa. Tulosten perusteella fyysisillä (sekä fysikaalisilla) työoloilla on merkittävä vaikutus yhteiskuntaluokkien välisiin eroihin yleisessä sairastavuudessa, toimintakyvyn heikentymisessä, tuki- ja liikuntaelinsairastavuudessa sekä itsearvioidussa terveydentilassa. Naisilla lähes puolet heikentyneen toimintakyvyn ja koetun terveydentilan luokkaeroista vaikutti olevan selitettävissä fyysisellä työkuormituksella. Hallintamahdollisuuksien ei havaittu merkittävästi muuttavan fyysisen kuormituksen vaikutusta toimintakykyyn. Fyysisen kuormittavuuden terveysvaikutus voimistui kasvavan iän mukaan enemmän naisilla kuin miehillä. Osa, mutta ei koko fyysisen kuormituksen vaikutus yhteiskuntaluokkien eroihin heikentyneessä terveydessä vaikutti välittyvän tuki- ja liikuntaelinsairastavuuden kautta. Terveys ja sairaus eivät ole yhtenäisiä tiloja, ja siksi monet eri sosiaalisesti ja rakenteellisesti määräytyvät olosuhteet todennäköisesti vaikuttavat yhteiskunnallisten terveyserojen syntymiseen. Fyysis-materiaalisten olojen vaikutusta terveyserojen syntyyn nyky-yhteiskunnassa on mahdollisesti aliarvioitu. Yhteiskuntaluokkien väliset erot fyysis-materiaalisissa olosuhteissa eivät ole kadonneet, ja nämä erot todennäköisesti vaikuttavat terveyserojen syntyyn.

Trends and Explanations for Socioeconomic Differences in Physical Activity

Very limited scientific knowledge exists on the trends and explanations of socioeconomic differences in physical activity among adults. There is a paucity of studies examining whether determinants vary across socioeconomic position and different life stages. This study examines a) how socioeconomic differences in leisure-time and commuting physical activity have changed in Finland from 1978 to 2002 and b) the contribution of childhood socioeconomic position, adolescence sports and exercise, adulthood socioeconomic position, working conditions and other adulthood health behaviours to socioeconomic differences in leisure-time physical activity. This study utilised three population-based datasets collected by the National Institute for Health and Welfare (THL, formerly National Institute for Public Health): the Health Behaviour and Health among the Finnish Adult Population Study from 1978 to 2002 (N=96 105), the National FINRISK Study 2002 and its physical activity sub-study (N= 9 179), and the Health 2000 Study (N=8 028). Survey information was collected by self-administered questionnaires, interviews at home, and measurements made at the study site. The response rates varied from 69 to 89 per cent. Several socioeconomic measures were linked from the national population registers. Based on the results, those with low income were physically inactive during leisure-time and while commuting from 1978 to 2002. Manual worker women, however, were more physically active commuters compared to their counterparts. Parental socioeconomic position contributed directly to adulthood educational differences in leisure-time physical inactivity but also indirectly through adulthood socioeconomic position (occupation, household income) and other unhealthy behaviours (mainly smoking). Among those with low education participation in competitive sports in youth and among those with high education exercise in late adolescence contributed to leisure-time physical activity in adulthood. Long exposure to physically strenuous working conditions in men and current job strain in women contributed to occupational class differences in leisure-time physical activity. Socioeconomic differences in physical activity have remained similar for twenty years in Finland. Educational career seems to have a strong contribution to physical activity. To adopt a lifelong physically active life-style, one should participate in a range of different sports and exercise in adolescence and in youth, have a low exposure to physically and mentally strenuous working conditions in later life and have other healthy behaviours in later life.

Physical activity, fitness, abdominal obesity, and cardiovascular risk factors in Finnish men and women : The National FINRISK 2002 Study

Physical inactivity, low cardiorespiratory fitness, and abdominal obesity are direct and mediating risk factors for cardiovascular disease (CVD). The results of recent studies suggest that individuals with higher levels of physical activity or cardiorespiratory fitness have lower CVD and all-cause mortality than those with lower activity or fitness levels regardless of their level of obesity. The interrelationships of physical activity, fitness, and abdominal obesity with cardiovascular risk factors have not been studied in detail. The aim of this study was to investigate the associations of different types of leisure time physical activity and aerobic fitness with cardiovascular risk factors in a large population of Finnish adults. In addition, a novel aerobic fitness test was implemented and the distribution of aerobic fitness was explored in men and women across age groups. The interrelationships of physical activity, aerobic fitness and abdominal obesity were examined in relation to cardiovascular risk factors. This study was part of the National FINRISK Study 2002, which monitors cardiovascular risk factors in a Finnish adult population. The sample comprised 13 437 men and women aged 25 to 74 years and was drawn from the Population Register as a stratified random sample according to 10-year age groups, gender and area. A separate physical activity study included 9179 subjects, of whom 5 980 participated (65%) in the study. At the study site, weight, height, waist and hip circumferences, and blood pressure were measured, a blood sample was drawn, and an aerobic fitness test was performed. The fitness test estimated maximal oxygen uptake (VO2max) and was based on a non-exercise method by using a heart rate monitor at rest. Waist-to-hip ratio (WHR) was calculated by dividing waist circumference with hip circumference and was used as a measure of abdominal obesity. Participants filled in a questionnaire on health behavior, a history of diseases, and current health status, and a detailed 12-month leisure time physical activity recall. Based on the recall data, relative energy expenditure was calculated using metabolic equivalents, and physical activity was divided into conditioning, non-conditioning, and commuting physical activity. Participants aged 45 to 74 years were later invited to take part in a 2-hour oral glucose tolerance test with fasting insulin and glucose measurements. Based on the oral glucose tolerance test, undiagnosed impaired glucose tolerance and type 2 diabetes were defined. The estimated aerobic fitness was lower among women and decreased with age. A higher estimated aerobic fitness and a lower WHR were independently associated with lower systolic and diastolic blood pressure, lower total cholesterol and triglyceride levels, and with higher high-density lipoprotein (HDL) cholesterol and HDL to total cholesterol ratio. The associations of the estimated aerobic fitness with diastolic blood pressure, triglycerides, and HDL to total cholesterol ratio were stronger in men with a higher WHR. High levels of conditioning and non-conditioning physical activity were associated with lower high-sensitivity C-reactive protein (CRP) levels. High levels of conditioning and overall physical activities were associated with lower insulin and glucose levels. The associations were stronger among women than men. A better self-rated physical fitness was associated with a higher estimated aerobic fitness, lower CRP levels, and lower insulin and glucose levels in men and women. In each WHR third, the risk of impaired glucose tolerance and type 2 diabetes was higher among physically inactive individuals who did not undertake at least 30 minutes of moderate-intensity physical activity on five days per week. These cross-sectional data show that higher levels of estimated aerobic fitness and regular leisure time physical activity are associated with a favorable cardiovascular risk factor profile and that these associations are present at all levels of abdominal obesity. Most of the associations followed a dose-response manner, suggesting that already low levels of physical activity or fitness are beneficial to health and that larger improvements in risk factor levels may be gained from higher activity and fitness levels. The present findings support the recommendation to engage regularly in leisure time physical activity, to pursue a high level of aerobic fitness, and to prevent abdominal obesity.

Physical characterization of plastic surfaces in wearing and cleanability research

Plastic surfaces are a group of materials used for many purposes. The present study was focused on methods for investigation of surface topography, wearing and cleanability of polyvinyl chloride (PVC) model surfaces and industrial plastic surfaces. Contact profilometry, scanning electron microscopy (SEM) and atomic force microscopy (AFM) are powerful methods for studying the topography of plastic surfaces. Although they have their own limitations, they are together an effective tool providing useful information on surface topography, especially when studying laboratory-made PVC model surfaces with known chemical compositions and structures. All examined laboratory-made PVC plastic surfaces examined in this work could be considered as smooth according to both AFM and profilometer measurements because height differences are in the nanoscale on every surface. Industrial plastic surfaces are a complex group of materials because of their chemical and topographical heterogeneity, but they are nevertheless important reference materials when developing cleaning and wearing methods. According to the results of this study the Soiling and Wearing Drum and the Frick-Taber methods are very useful when simulating three-body wearing of plastic surfaces. Both the investigated wearing methods can be used to compare the wearing of different plastic materials using appropriate evaluation methods of wearing and industrial use. In this study, physical methods were developed and adapted from other fields of material research to cleanability studies. The thesis focuses on the methodology for investigating the cleanability of plastic surfaces under realistic conditions, where surface topography and the effect of wear cleanability were among the major topics. A colorimetric method proved to be suitable for examining the cleanability of the industrial plastic surfaces. The results were utilized to evaluate the relationship between cleanability and the surface properties of plastic surfaces. The devices and methods used in the work can be utilized both in material research and product development.

Reduced visual function and its association with physical functioning in the Finnish adult population : Prevalence, causes, and need for eye care services

The purpose of this study was to estimate the prevalence and distribution of reduced visual acuity, major chronic eye diseases, and subsequent need for eye care services in the Finnish adult population comprising persons aged 30 years and older. In addition, we analyzed the effect of decreased vision on functioning and need for assistance using the World Health Organization’s (WHO) International Classification of Functioning, Disability, and Health (ICF) as a framework. The study was based on the Health 2000 health examination survey, a nationally representative population-based comprehensive survey of health and functional capacity carried out in 2000 to 2001 in Finland. The study sample representing the Finnish population aged 30 years and older was drawn by a two-stage stratified cluster sampling. The Health 2000 survey included a home interview and a comprehensive health examination conducted at a nearby screening center. If the invited participants did not attend, an abridged examination was conducted at home or in an institution. Based on our finding in participants, the great majority (96%) of Finnish adults had at least moderate visual acuity (VA ≥ 0.5) with current refraction correction, if any. However, in the age group 75–84 years the prevalence decreased to 81%, and after 85 years to 46%. In the population aged 30 years and older, the prevalence of habitual visual impairment (VA ≤ 0.25) was 1.6%, and 0.5% were blind (VA < 0.1). The prevalence of visual impairment increased significantly with age (p < 0.001), and after the age of 65 years the increase was sharp. Visual impairment was equally common for both sexes (OR 1.20, 95% CI 0.82 – 1.74). Based on self-reported and/or register-based data, the estimated total prevalences of cataract, glaucoma, age-related maculopathy (ARM), and diabetic retinopathy (DR) in the study population were 10%, 5%, 4%, and 1%, respectively. The prevalence of all of these chronic eye diseases increased with age (p < 0.001). Cataract and glaucoma were more common in women than in men (OR 1.55, 95% CI 1.26 – 1.91 and OR 1.57, 95% CI 1.24 – 1.98, respectively). The most prevalent eye diseases in people with visual impairment (VA ≤ 0.25) were ARM (37%), unoperated cataract (27%), glaucoma (22%), and DR (7%). One-half (58%) of visually impaired people had had a vision examination during the past five years, and 79% had received some vision rehabilitation services, mainly in the form of spectacles (70%). Only one-third (31%) had received formal low vision rehabilitation (i.e., fitting of low vision aids, receiving patient education, training for orientation and mobility, training for activities of daily living (ADL), or consultation with a social worker). People with low vision (VA 0.1 – 0.25) were less likely to have received formal low vision rehabilitation, magnifying glasses, or other low vision aids than blind people (VA < 0.1). Furthermore, low cognitive capacity and living in an institution were associated with limited use of vision rehabilitation services. Of the visually impaired living in the community, 71% reported a need for assistance and 24% had an unmet need for assistance in everyday activities. Prevalence of ADL, instrumental activities of daily living (IADL), and mobility increased with decreasing VA (p < 0.001). Visually impaired persons (VA ≤ 0.25) were four times more likely to have ADL disabilities than those with good VA (VA ≥ 0.8) after adjustment for sociodemographic and behavioral factors and chronic conditions (OR 4.36, 95% CI 2.44 – 7.78). Limitations in IADL and measured mobility were five times as likely (OR 4.82, 95% CI 2.38 – 9.76 and OR 5.37, 95% CI 2.44 – 7.78, respectively) and self-reported mobility limitations were three times as likely (OR 3.07, 95% CI 1.67 – 9.63) as in persons with good VA. The high prevalence of age-related eye diseases and subsequent visual impairment in the fastest growing segment of the population will result in a substantial increase in the demand for eye care services in the future. Many of the visually impaired, especially older persons with decreased cognitive capacity or living in an institution, have not had a recent vision examination and lack adequate low vision rehabilitation. This highlights the need for regular evaluation of visual function in the elderly and an active dissemination of information about rehabilitation services. Decreased VA is strongly associated with functional limitations, and even a slight decrease in VA was found to be associated with limited functioning. Thus, continuous efforts are needed to identify and treat eye diseases to maintain patients’ quality of life and to alleviate the social and economic burden of serious eye diseases.

On the behaviour of some physical parameterization methods in high-resolution numerical weather prediction models

Modern-day weather forecasting is highly dependent on Numerical Weather Prediction (NWP) models as the main data source. The evolving state of the atmosphere with time can be numerically predicted by solving a set of hydrodynamic equations, if the initial state is known. However, such a modelling approach always contains approximations that by and large depend on the purpose of use and resolution of the models. Present-day NWP systems operate with horizontal model resolutions in the range from about 40 km to 10 km. Recently, the aim has been to reach operationally to scales of 1 4 km. This requires less approximations in the model equations, more complex treatment of physical processes and, furthermore, more computing power. This thesis concentrates on the physical parameterization methods used in high-resolution NWP models. The main emphasis is on the validation of the grid-size-dependent convection parameterization in the High Resolution Limited Area Model (HIRLAM) and on a comprehensive intercomparison of radiative-flux parameterizations. In addition, the problems related to wind prediction near the coastline are addressed with high-resolution meso-scale models. The grid-size-dependent convection parameterization is clearly beneficial for NWP models operating with a dense grid. Results show that the current convection scheme in HIRLAM is still applicable down to a 5.6 km grid size. However, with further improved model resolution, the tendency of the model to overestimate strong precipitation intensities increases in all the experiment runs. For the clear-sky longwave radiation parameterization, schemes used in NWP-models provide much better results in comparison with simple empirical schemes. On the other hand, for the shortwave part of the spectrum, the empirical schemes are more competitive for producing fairly accurate surface fluxes. Overall, even the complex radiation parameterization schemes used in NWP-models seem to be slightly too transparent for both long- and shortwave radiation in clear-sky conditions. For cloudy conditions, simple cloud correction functions are tested. In case of longwave radiation, the empirical cloud correction methods provide rather accurate results, whereas for shortwave radiation the benefit is only marginal. Idealised high-resolution two-dimensional meso-scale model experiments suggest that the reason for the observed formation of the afternoon low level jet (LLJ) over the Gulf of Finland is an inertial oscillation mechanism, when the large-scale flow is from the south-east or west directions. The LLJ is further enhanced by the sea-breeze circulation. A three-dimensional HIRLAM experiment, with a 7.7 km grid size, is able to generate a similar LLJ flow structure as suggested by the 2D-experiments and observations. It is also pointed out that improved model resolution does not necessary lead to better wind forecasts in the statistical sense. In nested systems, the quality of the large-scale host model is really important, especially if the inner meso-scale model domain is small.

Straw Performance Studies and Quality Assurance for the ATLAS Transition Radiation Tracker

The Transition Radiation Tracker (TRT) of the ATLAS experiment at the LHC is part of the Inner Detector. It is designed as a robust and powerful gaseous detector that provides tracking through individual drift-tubes (straws) as well as particle identification via transition radiation (TR) detection. The straw tubes are operated with Xe-CO2-O2 70/27/3, a gas that combines the advantages of efficient TR absorption, a short electron drift time and minimum ageing effects. The modules of the barrel part of the TRT were built in the United States while the end-cap wheels are assembled at two Russian institutes. Acceptance tests of barrel modules and end-cap wheels are performed at CERN before assembly and integration with the Semiconductor Tracker (SCT) and the Pixel Detector. This thesis first describes simulations the TRT straw tube. The argon-based acceptance gas mixture as well as two xenon-based operating gases are examined for its properties. Drift velocities and Townsend coefficients are computed with the help of the program Magboltz and used to study electron drift and multiplication in the straw using the software Garfield. The inclusion of Penning transfers in the avalanche process leads to remarkable agreements with experimental data. A high level of cleanliness in the TRT s acceptance test gas system is indispensable. To monitor gas purity, a small straw tube detector has been constructed and extensively used to study the ageing behaviour of the straw tube in Ar-CO2. A variety of ageing tests are presented and discussed. Acceptance tests for the TRT survey dimensions, wire tension, gas-tightness, high-voltage stability and gas gain uniformity along each individual straw. The thesis gives details on acceptance criteria and measurement methods in the case of the end-cap wheels. Special focus is put on wire tension and straw straightness. The effect of geometrically deformed straws on gas gain and energy resolution is examined in an experimental setup and compared to simulation studies. An overview of the most important results from the end-cap wheels tested up to this point is presented.

Understanding the chemistry of atmospheric aerosol particle formation via observations of physical properties

It is widely accepted that the global climate is heating up due to human activities, such as burning of fossil fuels. Therefore we find ourselves forced to make decisions on what measures, if any, need to be taken to decrease our warming effect on the planet before any irrevocable damage occurs. Research is being conducted in a variety of fields to better understand all relevant processes governing Earth s climate, and to assess the relative roles of anthropogenic and biogenic emissions into the atmosphere. One of the least well quantified problems is the impact of small aerosol particles (both of anthropogenic and biogenic origin) on climate, through reflecting solar radiation and their ability to act as condensation nuclei for cloud droplets. In this thesis, the compounds driving the biogenic formation of new particles in the atmosphere have been examined through detailed measurements. As directly measuring the composition of these newly formed particles is extremely difficult, the approach was to indirectly study their different characteristics by measuring the hygroscopicity (water uptake) and volatility (evaporation) of particles between 10 and 50 nm. To study the first steps of the formation process in the sub-3 nm range, the nucleation of gaseous precursors to small clusters, the chemical composition of ambient naturally charged ions were measured. The ion measurements were performed with a newly developed mass spectrometer, which was first characterized in the laboratory before being deployed at a boreal forest measurement site. It was also successfully compared to similar, low-resolution instruments. The ambient measurements showed that sulfuric acid clusters dominate the negative ion spectrum during new particle formation events. Sulfuric acid/ammonia clusters were detected in ambient air for the first time in this work. Even though sulfuric acid is believed to be the most important gas phase precursor driving the initial cluster formation, measurements of the hygroscopicity and volatility of growing 10-50 nm particles in Hyytiälä showed an increasing role of organic vapors of a variety of oxidation levels. This work has provided additional insights into the compounds participating both in the initial formation and subsequent growth of atmospheric new aerosol particles. It will hopefully prove an important step in understanding atmospheric gas-to-particle conversion, which, by influencing cloud properties, can have important climate impacts. All available knowledge needs to be constantly updated, summarized, and brought to the attention of our decision-makers. Only by increasing our understanding of all the relevant processes can we build reliable models to predict the long-term effects of decisions made today.