Asthmatics as a susceptible population in health risk assessment of airborne chemicals

Asthma is a common chronic airway disease and about 235-300 million individuals of all ages are affected by the disease around the world. A precondition of asthma has been suggested to increase individual susceptibility to acute exposure from airborne irritant chemicals. In the health risk assessments of such chemicals, acute guideline values are derived to guide in preparedness and in emergency response, and to protect the general population, including susceptible subpopulations such as asthmatics. Experimental data on susceptible subpopulations are lacking for many chemicals and default inter-individual assessment factors (AFs) have been applied in the derivation of guideline values. However, the scientific basis for these default AFs in regard to asthmatics has been inadequate. The aims of this thesis were threefold. First, to study the extent to which experimental data regarding chemicals tested on asthmatics are included in the derivation of different sets of acute to short-term guideline values, and second, to determine whether there is a general difference in the airway response between healthy and asthmatic individuals, and whether current AFs for inter-individual variability provide sufficient protection for asthmatics. Last, to gain more knowledge on the susceptibility of asthmatics by measuring the airway response to chlorine in naïve and allergen-sensitized mice. In Paper I, the analysis of how asthmatics are considered in the derivation of Acute Exposure Guideline Levels (AEGLs) reveals that only 14 of 250 chemicals in the support documents had been tested on asthmatic subjects in experimental studies. A comparison between the AEGL support documents and nine other sets of acute to short-term guideline values shows that all of them were incomplete with respect to experimental data on asthmatics. In Paper II, experimental studies in which both healthy and asthmatic subjects were tested under the same conditions served as the basis for evaluating the lowest observed adverse effect concentrations (LOAECs) for healthy subjects and for asthmatic subjects. The ratios of these LOAECs were calculated and presented as estimated differential response factors (EDRFs). We found evidence of higher sensitivity among asthmatics (EDRF > 1) to 8 of 19 tested chemicals, and to 3 of 11 mixtures. Thereafter, concentration–response relationships confirmed the higher sensitivity of asthmatics to sulfuric acid and sulfur dioxide, and the Benchmark concentration (BMC) analysis of sulfur dioxide indicated a nine fold higher sensitivity among asthmatics. In Paper III, the consideration of asthmatics in the Derived NoEffect Levels (DNEL), developed under the European Union (EU) registration, evaluation, authorization and restriction of chemicals (REACH) legislation revealed that only 14 registered chemicals had been tested on asthmatics in experimental studies. Many of the DNELs for acute inhalation were higher than our estimated overall LOAEC or no observed adverse effect concentrations (NOAECs) in asthmatics, indicating a low or no safety margin. The experimental asthma model in Paper IV showed that exposure to 80 ppm of chlorine in naïve (but not OVA-sensitized) mice resulted in increased airway responsiveness and elevated numbers of neutrophils in the bronchoalveolar lavage fluid. Concentrationdependent reductions in respiratory frequency were seen in both groups. These results do not support an increased susceptibility to chlorine among mice with induced eosinophilic airway inflammation. Exclusion of asthmatics in the derivation of acute to short-term guideline values may interfere with trustful and efficient health-protective actions. The use of an AF of 10 when there is a lack of experimental data on asthmatics may be adequate to protect this subpopulation from the deleterious respiratory effects of airborne chemicals

Patients' knowledge and perceived understanding – Associations with consenting to participate in cancer clinical trials

AbstractRecruitment to clinical trials is essential. The aims of the study were to investigate associations between patients' informed consent to participate in a cancer clinical trial and knowledge and perceived understanding of the trial. Furthermore, associations between demographic factors and consent to participate and knowledge and perceived understanding of information about the trial were studied.MethodsThe patients were recruited in connection to a visit at the oncology clinic for information about a drug trial. The Quality of Informed Consent questionnaire was mailed to the patients after they had decided about participation in the trial. The associations of demographic factors and “knowledge” and “perceived understanding” were analysed using linear regression models.ResultsA total of 125 patients were included. Higher levels of “knowledge” and “understanding” were found to be associated with consent to participate in a clinical trial, both in the univariate and multivariate analyses (p = 0.001). None of the tested demographic factors were related to consent to participate. No statistically significant associations between any of the demographic factors and knowledge or perceived understanding scores were found.ConclusionThe results indicate that interventions that increase patients' knowledge and perceived understanding might improve participation rates in clinical trials

Mental adjustment to cancer and its relation to anxiety, depression, HRQL and survival in patients with laryngeal cancer - A longitudinal study

<p>Abstract</p> <p>Background</p> <p>Using a longitudinal design, aim of this study was to investigate the relation between mental adjustment to cancer and anxiety, depression, health-related quality of life (HRQL) and survival in patients treated for laryngeal cancer.</p> <p>Methods</p> <p>95 patients with Tis-T4 laryngeal cancer were assessed at one and 12 months after start of treatment, respectively, using the Mini-Mental Adjustment to Cancer Scale (Mini-MAC), the European Organisation for Research and Treatment of Cancer (EORTC) Study Group on Quality of Life core questionnaire (EORTC QLQ-C30) supplemented with the Head and Neck cancer module (QLQ-H&N35) and the Hospital Anxiety and Depression (HAD) Scale. For survival analyses patients were followed up for a median time of 4.22 years from inclusion.</p> <p>Results</p> <p>The most commonly used adjustment response at both occasions was Fighting Spirit. The use of adjustment responses was relatively stable over time. Correlation analyses showed that patients using Helpless-Hopeless and Anxious Preoccupation responses reported more anxiety and depression, as well as decreased HRQL. Tumour site and stage showed no effect on adjustment response. Survival analysis indicated that use of a Helpless-Hopeless response was related to poorer survival (HR 1.17, p 0.001).</p> <p>Conclusion</p> <p>The relation between adjustment responses Helpless-Hopeless and Anxious Preoccupation and anxiety, depression, HRQL and possibly poorer survival indicate that assessment of mental adjustment should be considered when planning treatment and rehabilitation in laryngeal cancer patients.</p

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Kunskapsarbetaren - En nyanserande studie

Syfte: Med utgångspunkt i empirifynd argumentera för en mer nyanserad bild av kunskapsindividen inom den kunskapsintensiva organisationen för att kritiskt granska den befintliga litterära bilden av kunskapsarbetaren. Metod: För att genomföra vår undersökning har vi utfört kvalitativa, semi-strukturerade intervjuer i två kunskapsintensiva organisationer. Teori: Vi framhäver den befintliga positiva bilden av autonomi genom Motivationsteori, Efterföljarskapsteori, Ledarskaps- Substitutionsteori, Kunskapsteori, Kunskapsintensiva kontexten, Arbetsnöjdhetsteori samt som teoretiskt perspektiv Identitetsteori. Empiri: Vår empiri består av sex semi-strukturerade kvalitativa intervjuer, varav två av dessa var med chefer medan de resterande var med kunskapsarbetare, från två olika organisationer. Resultat: Resultatet tyder på, i motsatts till befintlig teori, att kunskapsarbetarna fann den överhängande autonomin i självständighet, beslut, ansvar och kompetens vid flera situationer vara betungande och inte ständigt positivt. Det resulterade i begreppsbildning av Kunskapsensamhet samt Autonomiensamhet som består av Frihetsensamhet, Ansvarsensamhet och Beslutsensamhet

Co-Designing with Extreme Users: A Framework for User Participation in Design Processes

The demand for user participation in design processes is increasing, and there is a need to formulate guidance on how to involve disabled users and their representative organisations. Their participation contributes an extreme user perspective to the design process. The aim of this study was to develop an empirically grounded framework for user participation in co-design processes, involving the users with wide range of characteristics. The study was theoretically grounded in ‘participatory design’ and ‘value sensitive design’ and used an exploratory study design with online workshops to iteratively collect and analyse data. All participants collaborated on an online Miro-board to identify themes and formulate guiding principles for the framework. We propose a framework consisting of three themes: participation fundamentals, participation ethics and participation practicalities, entailing 11 guiding principles. By applying this framework, the premises, methods and activities in the design process will be accessible to all participants, and user participation in design projects will become more transparent, equitable and easier to implement. It will enable all users, people with disabilities and others, to participate and contribute to a design that can be used by the widest range of people

Astatine-211 based radionuclide therapy: Current clinical trial landscape

Astatine-211 (211At) has physical properties that make it one of the top candidates for use as a radiation source for alpha particle-based radionuclide therapy, also referred to as targeted alpha therapy (TAT). Here, we summarize the main results of the completed clinical trials, further describe ongoing trials, and discuss future prospects

Manoeuvring between anxiety and control: Patients&apos; experience of learning to live with diabetes: A lifeworld phenomenological study

Abstract Research shows that people with diabetes want their lives to proceed as normally as possible, but some patients experience difficulty in reaching their desired goals with treatment. The learning process is a complex phenomenon interwoven into every facet of life. Patients and healthcare providers often have different perspectives in care which gives different expectations on what the patients need to learn and cope with. The aim of this study, therefore, is to describe the experience of learning to live with diabetes. Interviews were conducted with 12 patients afflicted with type 1 or type 2 diabetes. The interviews were then analysed with reference to the reflective lifeworld research approach. The analysis shows that when the afflicted realize that their bodies undergo changes and that blood sugar levels are not always balanced as earlier in life, they can adjust to their new conditions early. The afflicted must take responsibility for balancing their blood sugar levels and incorporating the illness into their lives. Achieving such goals necessitates knowledge. The search for knowledge and sensitivity to changes are constant requirements for people with diabetes. Learning is driven by the tension caused by the need for and dependence on safe blood sugar control, the fear of losing such control, and the fear of future complications. The most important responsibilities for these patients are aspiring to understand their bodies as lived bodies, ensuring safety and security, and acquiring the knowledge essential to making conscious choices

Vargstammen i Finland i mars 2023

I mars 2023 fanns det i Finland med största sannolikhet totalt 62 revir med revirmarkerande par eller familjegrupper (59–64 med konfidensgrad 90 %). Det mest sannolika antalet familjegrupper var 42 (40–46) och antalet parrevir var 19 (16–23). På enbart finskt territorium levde 35 familjegrupper (33–39) och 17 par (14–21). På vardera sidan av den östra riksgränsen fanns sju (6–7) s.k. gränsrevir med revirmarkerande flockar och två (2–3) med revirmarkeran-de par. I västra Finland fanns 28 (26–31) revir med familjegrupper och 11 (8–14) revir med revirmarkerande par; på motsvarande sätt uppskattades att det i östra Finland fanns 13 (12–14) revir med familjegrupper och åtta (6–10) revir med revirmarkerande par. I renskötselområdet rörde sig sannolikt en (0–1) revirmarkerande familjegrupp. Antalet familjegrupper som påträffades i Finland i mars 2023 var cirka 14 procent större än i mars 2022. Antalet par hade minskat med cirka 17 procent jämfört med år 2022. Vid jämförelse av det mest sannolika antalet flockar som helt lever på finskt territorium kan en ökning på 9 procent konstateras jämfört med året innan, medan antalet par som lever helt på finskt territorium har minskat med 19 procent. Sedan millennieskiftet har storleken på vargstammen i Finland varierat kraftigt. Efter 2017 har antalet vargar ökat kontinuerligt. Bedömningen av revirstatus (familjegrupp, par) och antalet individer i flockarna gjordes utifrån observationer från varje granskat område, känd dödlighet och dna-analyser. Dessutom utfördes separat terrängarbete på en del av reviren. Under vargens årscykel är antalet vargar som minst i mars, före valpningen i april–maj. Förändringarna i vargstammen efter mars beskrivs med en populationsmodell som bygger på forskningsdata om vargens valpantal och dödlighet. Utan stamvårdande jakt kommer det enligt beräkningarna att i november 2023 finnas 30–55 familjegrupper (90 % sannolikhet) och i mars 2024 mellan 27–51 familjegrupper

Vargstammen i Finland i mars 2022

I mars 2022 fanns det i Finland med största sannolikhet totalt 60 revir med revirmarkerande par eller familjegrupper (57–63 med konfidensgrad 90 %). Det mest sannolika antalet familjegrupper var 37 (34–41) och antalet parrevir var 23 (19–27). På enbart finskt territorium levde 32 familjegrupper (29–36 med konfidensgrad 90 %) och 21 par (17–24 med konfidensgrad 90 %). På vardera sidan av den östra riksgränsen fanns fyra s.k. gränsrevir med revirmarkerande flockar (3–5) och tre med revirmarkerande par (2–4). I västra Finland fanns 26 (23–29) revir med familjegrupper och 15 (12–18) revir med revirmarkerande par, på motsvarande sätt uppskattades att det i östra Finland fanns 11 (10–13) revir med familjegrupper och 8 (6–9) revir med revirmarkerande par. I renskötselområdet rörde sig sannolikt ett (0–2) revirmarkerande par. Antalet familjegrupper som påträffades i Finland i mars 2022 var det samma som i mars 2021. Vid jämförelse av det mest sannolika antalet flockar som helt lever på finskt territorium kan en ökning på 7 procent konstateras jämfört med året innan. Antalet revirmarkerande par hade enligt beräkningarna ökat med cirka 17 procent jämfört med år 2021. Under det innevarande årtusendet har storleken på vargstammen i Finland varierat kraftigt. Efter 2017 har antalet vargar ökat kontinuerligt. Bedömningen av revirstatus (familjegrupp, par) och antalet individer i flockarna gjordes utifrån observationer från varje granskat område, känd dödlighet och DNA-analyser. Dessutom utfördes separat terrängarbete på en del av reviren. Antalet vargar är under vargens årscykel lägst i mars, före valpningen i april–maj. Förändringarna i vargstammen efter mars beskrivs med en prognosmodell som bygger på forskningsdata om vargens valpresultat och dödlighet. I november 2022 kommer det med 90 procents sannolikhet att finnas 35–49 flockar. Vid utgången av mars 2023 finns det 20–42 flockar, med konfidensgraden 90 procent