People are, in their daily lives, exposed to a number of airborne foreign compounds that do not normally affect the body. However, depending on the nature of these compounds, dose and duration of exposure, various airway symptoms may arise. Early symptoms are often manifested as upper airway mucosal inflammation which generates changes in protein composition in the airway lining fluid. This thesis aims at identifying, understanding mechanisms and characterizing protein alterations in the upper airway mucosa that can be used as potential new biomarkers for inflammation in the mucosa. The protein composition in the mucosa was studied by sampling of nasal lavage fluid that was further analyzed with a proteomic approach using twodimensional gel electrophoresis and mass spectrometry. Additionally, by studying factors on site through environmental examination, health questionnaires and biological analyses, we have tried to understand the background to these protein alterations and their impact on health. Respiratory symptoms from the upper airways are common among people who are exposed to irritative and microbial agents. This thesis have focused on personnel in swimming pool facilities exposed to trichloramine, metal industry workers exposed to metalworking fluids, employees working in damp and moldy buildings and infants diagnosed with respiratory syncytial virus infection. The common denominator in these four studies is that the subjects experience upper airway mucosal inflammation, which is manifested as cough, rhinitis, phlegm etc. In the three occupational studies, the symptoms were work related. Notably, a high prevalence of perceived mucosal symptoms was shown despite the relatively low levels of airborne irritants revealed by the environmental examination. Protein profiling verified an ongoing inflammatory response by identification of several proteins that displayed altered levels. Interestingly, innate immune proteins dominated and four protein alterations occurred in most of the studies; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin. Similarly, these proteins were also found in nasal fluid from children with virus infection and in addition a truncated form of SPLUNC1 and two other S100 proteins (S100A7-like 2 and S100A16), not previously found in nasal secretion, were identified. Altogether, the results indicate the potential use of a proteomic approach for identifying new biomarkers for the upper respiratory tract at an early stage in the disease process after exposure to irritant and microbial agents. The results indicate an effect on the innate immunity system and the proteins; SPLUNC1, protein S100A8 and S100A9 and alpha-1-antitrypsin are especially promising new biomarkers. Moreover, further studies of these proteins may help us to understand the molecular mechanisms involved in irritant-induced airway inflammation.

To prevent work-related musculoskeletal disorders (MSDs), useful, reliable and valid methods for assessing physical workload and risks for MSDs are needed. Ergonomists often assess work by short visual observations without a specific tool. A branch-specific tool was developed for assessing working technique during cash register work (BAsiK observation protocol). Inclinometers are an alternative for assessing upper arm postures - over several days. Ergonomists need guidelines explaining how to analyze and interpret such data. The aim was to examine and investigate methods for assessing physical load at work, with focus on the neck and upper extremities. In Paper: I, the reliability and criterion validity of the BAsIK observation protocol were assessed. II, the reliability of risk assessments of repetitive work, based on visual observations performed by 21 ergonomists without a specific tool, was assessed. III, whole-day inclinometer measurements of upper arm elevation were compared between work and leisure, across 13 different occupations – before and after arm elevations during sitting time was excluded. IV, the association between inclinometer-based upper arm elevation and neck/shoulder pain was assessed among 654 blue-collar workers.   The intra-observer reliability of the BAsIK protocol was deemed acceptable, but only 3 of 10 questions in the protocol showed acceptable inter-observer reliability, and 3 showed acceptable criterion validity. Neither the inter- or intra-observer reliability of risk assessment without any specific method was acceptable for any upper body regions. None of the occupation groups, in paper III, had higher proportion of time with arm elevation during work than leisure. However, when arm elevation during sitting was excluded, 8 occupation groups had higher proportion of time with elevated arms during work than leisure. Whole-workday inclinometer-based upper arm elevation was not associated with neck/shoulder pain within the assessed population.    The results indicate that, in most cases, a single visual observation of a work sequence is not a reliable means of assessing repetitive work. A large proportion of arm elevation may derive from sitting time. At low exposure levels, arm elevation per se may not be a risk factor for neck/shoulder pain. This must be taken into account when evaluating the risk for MSDs.

Background: Insufficient exposure assessment is a suggested contributing factor to the current lack of clearly characterised relationships between occupational biomechanical risk factors and musculoskeletal disorders. Minimal attention has been paid to the potential bias of measurement tools from expected true values (i.e. accuracy) or between measurement tools, and empirical data on the magnitudes of variance contributed by methodological factors for measurement tool precision are lacking. Aim: The aim of this thesis was to quantify aspects of bias and precision in three commonly employed biomechanical risk factor assessment tools - inclinometry, observation, and electromyography (EMG) - and provide recommendations guiding their use. Methods: Upper arm elevation angles (UAEAs) were assessed using inclinometers (INC) and by computer-based posture-matching observation, and bias relative to true angles was calculated. Calibration models were developed for INC data, and their efficacy in correcting measurement bias was evaluated. The total variance of trapezius and erector spinae (ES) EMG recordings during cyclic occupational work was partitioned into biological and methodological sources, including the variance uniquely attributable to sub-maximal normalisation. Using algorithms to estimate the precision of a group mean, the efficacy of different trapezius EMG study designs was evaluated. Using precision criteria, the efficacy of different normalisation methods was assessed for ES EMG recordings. Results and Discussion: Inclinometer measured UAEAs were biased from true angles, with increasing bias at higher angles. In contrast, computer based posture-matching observations were not biased from true angles.  Calibration models proved effective at minimizing INC data bias. The dispersion of estimates between- and within- observers at any given set angle underlined the importance of repeated observations when estimating UAEAs.  For EMG, a unique but relatively small component of the total variance was attributable to the methodological process of normalisation. Performing three repeats of the trapezius EMG normalisation task proved optimal at minimizing variance for one-day EMG studies, while two repeats sufficed for multi-day EMG studies. A prone normalisation task proved superior for maximizing normalised lumbar ES EMG precision. Conclusion: Key aspects of measurement tool accuracy, bias between tools, and tool precision were quantified, and recommendations were made to guide future research study design.

Aim: The aim of the thesis was to investigate the impact of gaze-based assistive technology on daily activities in children with severe physical impairments and without speech. The objectives were to develop and pilot a gaze-based assistive technology intervention (GAT intervention) at home and in school for these children and to understand its impact on daily activities as experienced by their parents. Methods: Study I was a pilot study in which the basic components that were developed for the intervention were evaluated for students with physical impairments. The study aimed at improving the use of computers as assistive technology (AT) in school. Based on the findings in Study I, the GAT intervention was developed. The GAT intervention aimed at implementing gaze-based AT in daily activities. It consisted of two parts; having access to gaze-based AT and having access to services from a multi professional communication team during nine to ten months. Studies II-IV concerned gazebased AT for children with severe physical impairments without speech who participated in the GAT intervention. The participants were ten children (ages 1-15) (Studies II, III), and their parents (Study IV). Studies II and III had longitudinal designs and children were followed during 15-20 months with repeated measurements before, after and at follow-up. In Study II children’s repertoire of computer activities, extent of use, and goal attainment with gaze-based AT was evaluated, as well as parents’ satisfaction with the AT and with services. In Study III children’s eye gaze performance when using gaze-based AT was examined. In Study IV, parents were interviewed twice with the aim of  exploring their experiences of children’s gaze-based AT use in daily life. In Study IV a hermeneutical approach was used. Results: The findings of Study I showed that the basic components of intervention improved the use of computers in school. Study II showed an increased repertoire of computer activities with the gazebased AT, maintained use in daily activities for all at follow up, and that all children attained goals for gaze-based AT use in daily activities. Parents were satisfied with the gaze-based AT, and with the services in the GAT intervention. In study III, nine children improved in eye gaze performance over time when using the gaze-based AT in daily activities. Study IV revealed that children’s gaze-based AT usage in daily activities made a difference to parents since the children demonstrated agency, and showed their personality and competencies by using gaze-based AT, and for the parents this opened up infinite possibilities for the child to do and learn things. Overall, children’s gaze-based AT usage provided parents with hope of a future in which their children could develop and have influence in life. Conclusions: This thesis shows that these children with severe physical impairments and without speech acquired sufficient gaze control skills to use gaze-based AT for daily activities in the home and at school. The gaze-based AT had a positive impact on performing activities, for example, play activities and communication- and interaction-related activities. For the parents, children’s gaze-based AT usage made a difference since it shaped a hope of a better future for their children, where they can develop and gain influence in their future life. Furthermore, the children continued to perform daily activities with gaze-based AT over time. This finding suggests that key persons were provided with sufficient knowledge and skills to support children in maintained use of gaze-based AT after withdrawal of the services provided in the GAT intervention.

Background In Swedish working life, exposure to cold and exposure to hand-arm vibration (HAV) are two common health hazards. Health effects of HAV in the neurosensory, vascular and musculoskeletal systems are collectively denoted hand-arm vibration syndrome (HAVS), and have been thoroughly studied. Effects of cold exposure in terms of effects on the peripheral neurosensory and vascular system are on the contrary limited, especially in an occupational setting. Effects of cold exposure or cold injury have not previously been assessed with quantitative sensory testing (QST). Commonly reported symptoms after exposure to HAV and after cold injuries, includes cold sensitivity and sensation of cold. Cold sensitivity can also occur without previous exposure to vibration or cold and may have a major impact on quality of life. Other possible risk factors for cold sensitivity need to be assessed. Sensation of cold hands could theoretically imply an early manifestation of damage to the neurosensory or vascular system, and therefore be of importance to enable early detection of vascular and neurosensory HAVS. The purpose of this thesis was to increase the knowledge about health effects from cold and HAV on the peripheral neurosensory and vascular system, with an occupational perspective. The aims were: first, to identify and evaluate health effects and sequelae in the peripheral neurosensory and vascular system due to cold injury and cold exposure; second, to investigate if sensation of cold hands is a predictor for future onset of Raynaud's phenomenon or paresthesia; and third, to identify possible risk factors associated with cold sensitivity. Methods A case series on 15 military conscripts with local cold injuries in the hands or feet, involving QST and symptom descriptions, was conducted to investigate the hypothesis that cold injuries can result in similar neurosensory and vascular impairments as in HAVS. To assess health effects of cold exposure, a cohort study on 54 military conscripts in cold winter military training, with cold exposure assessments, was conducted. Possible health effects were assessed after 14 months of military training, containing considerable cold exposure, by means of QST, Finger systolic blood pressure after local cooling (FSBP) and a questionnaire. To investigate if sensation of cold hands is a predictor for vascular or neurosensory HAVS we investigated a cohort of 178 employees at a manufacturing company where HAV was a common exposure. The cohort was followed during 21 years and both vibration exposure and health outcomes were assessed regularly. Questionnaire items were used to assess sensations of cold hands as well as signs of Raynaud’s phenomenon and paresthesia. To identify risk factors for cold sensitivity a case-control study was conducted involving 997iiiparticipants from the general population in northern Sweden. The study was cross-sectional and explored possible risk factors for cold sensitivity. Results Cold injuries and cold exposure were associated with reduced sensibility in QST and increase severity and prevalence of neurosensory and vascular symptoms. Our results did not show any impairment in peripheral blood flow due to cold exposure, detectable by FSBP. The risk of developing Raynaud's phenomenon was increased for workers previously reporting sensation of cold hands (OR 6.3, 95% CI 2.3-17.0). No increased risk for paresthesia in relation to a sensation of cold hands was observed. The identified risk factors for cold sensitivity were frostbite in the hands, rheumatic disease, nerve injury in upper extremities or neck, migraine and vascular disease. When analysing women and men separately, women’s risk factors were frostbite in the hands, rheumatic disease, migraine and cold exposure. Men’s risk factors were frostbite in the hands, vibration exposure and nerve injury in upper extremities or neck. BMI > 25 was a protective factor for both men and women. Conclusion Cold injury and cold exposure are associated with impairments in the neurosensory system, detectable by QST. Symptoms such as sensation of cold hands and white fingers indicate vascular involvement, even though no vascular impairments due to cold exposure could be detected by objective measurements. A sensation of cold hands is a risk factor for development of Raynaud´s phenomenon, but not for paresthesia. At the individual level, reporting cold hands does not appear to be useful information when considering the possibility of a future development of Raynaud’s phenomenon. Frostbite in the hands is a risk factor for cold sensitivity among both women and men. For women rheumatic disease, migraine and cold exposure are also independent risk factors, and for men, exposure to HAV. Being overweight is a protective factor for both women and men.