Genome Guided Personalized Drug Therapy in Attention Deficit Hyperactivity Disorder

ADHD is a common behavioral syndrome with a heritability of 70–80%. Genome wide sequencing and association studies indicate that ADHD risk variants are distributed across a wide range of allele frequencies and relative risks. Several common single nucleotide variants (SNPs) have been identified that increase the risk of ADHD with a few percent. Many of the reported risk genes and copy number variants are shared with other neuropsychiatric disorders. Moreover, ADHD often coexists with common or rare somatic diseases, including rare Mendelian neurometabolic diseases that can affect normal brain development and function. Some genetic/metabolic syndromes masquerading as common ADHD may lead to irreversible brain damage if not properly identified and treated during early childhood. As ADHD is such a heterogeneous condition in terms of severity, clinical features and most probably also underlying biology, it is crucial to offer individualized treatments. Recent progress in ADHD genetics is reviewed, prospects of using this information for targeted pharmacotherapy are discussed and critical knowledge gaps are identified. It is suggested that genome guided therapies could be introduced gradually, starting with rare ADHD syndromes with highly penetrant risk genes. Routine diagnostic application of whole exome or whole genome sequencing combined with metabolomic screening, and brain imaging may be needed in cases with suspected neurometabolic disorders. Identification and treatment of ADHD patients with defined neurometabolic aberrations could be a first step toward genome guided personalized treatment of ADHD. Possibly, screening for relevant biomarkers may gradually be implemented to guide treatment choices in larger patient groups.publishedVersio

Tidal breathing parameters in extremely premature infants. Feasibility and clinical utility of electromagnetic inductance plethysmography

Background: Extremely preterm (EP) birth is associated with adverse lung growth, due to disturbance of programmed and fine-tuned sequences of normal intrauterine development, as well as the trauma inflicted by life-saving treatments. Moreover, EP-born neonates are probably born with variable susceptibilities or predispositions for lung injury. The pulmonary consequences of EP birth are heterogeneous and insufficiently mapped and understood. Particularly, our understanding of the detailed lung mechanics in EP-born infants is limited, largely due to the fact that lung function measurements in neonates and infants are complex and not readily available. Electromagnetic inductance plethysmography (EIP) is a novel non-invasive system that provides tidal breathing parameters in the form of tidal flow volume loops. With these studies, we aimed to: (1) Study feasibility and validity of the EIP method in preterm and term-born infants, (2) use the EIP method to compare lung function in EP and term-born infants at term-equivalent age, and test if lung function measurements obtained at this stage in EP-born infants were associated with respiratory health during their first year of life, and (3) study if tidal breathing parameters, obtained from a mechanical ventilator during the few first hours of life in EP-born neonates, could predict bronchopulmonary dysplasia (BPD). Methods: In study #1, we tested repeatability of the EIP method in a total of 30 preterm born infants who were at various stages of their development. A nurse experienced with the system measured all patients before and after meals, and these measurements were repeated by nurses new to the system. In study #2, the EIP-method was validated against a ‘gold standard method’ (mask-based ultrasonic flowmeter) in 30 infants at postmenstrual ages between 36 to 43 weeks and weights from 2.3 to 4.8 kg, applying both methods simultaneously. In study #3, within a population-based design, 52 EP-born infants recruited at Haukeland and Stavanger University Hospitals had their lung function measured at term-equivalent age using the EIP method, and the results were compared with 45 term-born controls. The EP-born infants were followed during their first year of life, including clinical examinations and questionnaires addressing respiratory symptoms and treatments. In study #4, using custom made software, we calculated tidal breathing parameters from the flow signals of 33 ventilator treated EP born neonates during their first hours of life, and the data were compared between those who later developed moderate/severe versus no/mild BPD. Results: We found in studies #1 and #2 that the EIP method was well tolerated by the infants and also feasible in a busy NICU setting. The repeatability was better for term-born than preterm-born infants, but comparable to what has been reported for “maskbased” infant spirometry. The experience of the personnel and the relationship to meals influenced the reproducibility. Tidal breathing parameters obtained by the EIP method corresponded well with those obtained by the “mask-based” system when applied simultaneously in infants at term-equivalent age. In study #3, we found that lung function measured by EIP was strikingly abnormal in EP compared to healthy term-born infants at term-equivalent age, characterized by obstructive pulmonary abnormalities, and by increased tidal volumes and minute ventilation. Abnormalities were most pronounced for the group of infants with BPD, but significantly present also in infants without BPD. The tidal breathing parameter TEF50/PTEF predicted respiratory morbidity in the first year of life in infants born EP. In study #4, we found that flow data easily obtained from a ventilator during the first 48 hours of life could be used to compute breathing parameters that discriminated between neonates who went on to develop the severe forms of BPD and those who did not. Conclusions and implications: EIP emerges as a feasible method of infant lung function testing. Its major strengths are the relative simplicity by which it can be put to use, and the avoidance of a facemask. This thesis has demonstrated that EIP can provide tidal breathing measurements that can aid the characterization of lung disease after EP birth, and that tidal breathing parameters obtained shortly after birth may identify neonates with predisposition for a difficult clinical respiratory course. If subsequent evaluations were to confirm the findings of this thesis, EIP and tidal breathing parameters have the potential of early recognition of neonates at risk of the severe forms of lung disease of prematurity and of later respiratory morbidity, which may pave the way for lifelong targeted surveillance and guidance of clinical management and intervention studies

Use of a generic protocol in documentation of prescription errors in Estonia, Norway and Sweden

Beskriver en studie hvor hensikten var å evaluere egnethet av et generisk instrument for å dokumentere forskrivningsproblemer som krever kontakt med lege før utlevering.Pharmacists have an important role in detecting, preventing, and solving prescription problems, which if left unresolved, may pose a risk of harming the patient. Objective: the objectives of this study were to evaluate the feasibility of a generic study instrument for documentation of prescription problems requiring contact with prescriber before dispensing. The study was organized: 1) by countries: Estonia, Norway and Sweden; 2) by type of prescriptions: handwritten prescriptions, printouts of prescriptions in the electronic medical record and electronically transmitted prescriptions to pharmacies; and 3) by recording method - self-completion by pharmacists and independent observers. Methods: observational study with independent observers at community pharmacies in Estonia (n=4) and Sweden (n=7) and self-completed protocols in Norway (n=9). Results: pharmacists' in Estonia contacted the prescriber for 1.47% of the prescriptions, about 3 times as often as in Norway (0.45%) and Sweden (0.38%). Handwritten prescriptions dominated among the problem prescriptions in Estonia (73.2%), printouts of prescriptions in the electronic medical record (89.1%) in Norway and electronically transmitted prescriptions to pharmacies (55.9%) in Sweden. More administrative errors were identified on handwritten prescriptions and printouts of prescriptions in the electronic medical record in Estonia and in Norway compared with electronically transmitted prescriptions to pharmacies in Sweden (p<0.05 for prescription types and p<0.01 for countries). However, clinically important errors and delivery problems appeared equally often on the different types of prescriptions. In all three countries, only few cases of drug interactions and adverse drug reactions were identified. Conclusion: despite the different patterns of prescription problems in three countries, the instrument was feasible and can be regarded appropriate to document and classify prescription problems necessitating contact with prescriber before dispensing, irrespective of the type of prescription or recording method

Organisasjonssosialisering: En kvalitativ studie av samspillet mellom deltakerne i prosessene rundt organisasjonssosialisering i Bane NOR

Sammendrag Formålet med denne masteroppgaven er å undersøke uformelle og relasjonelle organisatoriske sosialiseringsprosesser, samt ansvaret og forventninger til de ulike aktørene som er involvert. Rolleklarhet, sosial integrasjon, mestring og kunnskap om kulturen oppnås gjennom uformelle praksiser slik som mellommenneskelige relasjoner (Bauer, 2010). Oppgaven er skrevet for Bane NOR (BN). I tider hvor onboardingsprosesser blir digitalisert, er det verdifullt å undersøke hvordan benytte seg av slike ressurser i en mer og mer fragmentert verden. Færre fysiske møter påvirker læringsprosessene for nyansatte. Organisasjoner burde forstå samspillet mellom aktørene som er en del av onboardingsprosesser. Gjennom problemstillingen Hvordan kan forutsetningene for en organisatorisk sosialiseringsprosess hos Bane NOR forbedres ved å ha en eksplisitt og proaktiv tilnærming til oppgaven? vil denne oppgaven bidra til å fremheve viktigheten av dette. Med en utforskende og deskriptiv tilnærming til problemstillingen, er studiet er basert på en kvalitativ metodikk. Datainnsamlingen ble utført ved å intervjue ni informanter som representerer de ulike aktørene som vi studerte, som er den nyansatte, lederen med ansvar for onboardingen og Human Resources (HR). I tillegg har vi samlet inn innsikt fra dokumenter og andre ansatte for å avdekke generelle hensyn knyttet til problemstillingen. Denne studien er basert på et humanistisk menneskesyn, der vi ser på ansatte som sosiale ressurser, i stand til å skape et positivt resultat for alle. Litteratur innenfor feltet viser at et godt grunnlag for onboarding inkluderer et samspill mellom nyansattes egenskaper, atferd og organisatorisk innsats (Bauer & Erdogan, 2011). Oppgaven er basert på Talya N. Bauer og Cathrine Filstads arbeid om organisasjonssosialisering, Cato Wadels litteratur om lærende organisasjoner, og Edgar H. Scheins teorier om organisasjonskultur. Tilleggslitteratur inkluderer felt som fysisk tilstedeværelse og autonomi da dette er faktorer som er relevante for den organisatoriske sosialiseringen i BN. Det vil ikke være mulig å trekke endelige konklusjoner fra et så lite utvalg, men det er mange funn som peker på trender som er spesifikke for denne organisasjonen og organisasjoner generelt. Analysen og resultatene som er basert på den empiriske datainnsamlingen peker på iv flere aspekter og behov som er viktige for onboardingen. Våre funn indikerer at BN kan med fordel dra nytte av økt læring fra eierne av problemene før de utvikler fremtidige strategier og processer for onboardingen. Lederne verdsetter deres autonomi og muligheten til å tilpasse prosessene til lokale behov. Selv om hver nyansatt, leder, team og organisasjon har sine egne egenskaper, er grunnlaget for en onboardingsprosess å legge til rette for sosial trygghet og etablere solide forbindelser. Vi vil hevde at BN med fordel kan legge vekt på individuelle behov og forventninger fra den nyansatte. Da vi forholder oss til organisasjonssosialisering som en læringsprosess som skjer mellom aktørene, er det viktig å etablere et felles grunnlag gjennom rolle- og forventningsavklaringer. Funnene viser også at formaliserte tiltak som bruk av sponsor, mentor og traineeprogrammer er elementer innen onboarding som bør være sentraliserte prosesser. Disse er i økt grad viktige med mindre fysisk tilstedeværelse. Ansvaret for sosialisering ligger mellom aktørene som kompetente individer og kjernen i sosialiseringen skjer gjennom kommunikasjon og gjensidige tilpasninger.The purpose of this thesis is to research the informal and relational organisational socialisation processes and the responsibilities and needs of the different actors involved. Role clarity, social integration, self-efficacy, and knowledge of culture are achieved through informal practices such as interpersonal relationships (Bauer, 2010). The thesis is conducted in collaboration with Bane NOR (BN). In times when onboarding processes are being digitised, it is valuable to investigate how to utilise such resources in an increasingly fragmented world. Remote work and less physical interaction affect the learning process for new employees. Organisations should understand the interplay between the actors that are a part of an onboarding process. Through the statement How can the conditions for an organisational socialisation process be improved at Bane NOR by taking an explicit and proactive approach to the task? this thesis will contribute to emphasise the importance of such. With an exploratory and descriptive approach to the issue, the study is based on a qualitative methodology. Data collection was conducted by interviewing nine informants that represent the different actors that we were studying, which are the new employee, the manager responsible for the onboarding, and the Human Resources (HR). Additionally, we gathered insights from documents and other employees to uncover general considerations linked to the issue. This study is based on a humanistic view of humanity where we view employees as social resources, capable of creating a positive outcome for all. Literature within the field shows that a solid basis for onboarding practices includes an interplay between new employee characteristics, behaviours, and organisational efforts (Bauer & Erdogan, 2011). The thesis is based on Talya N. Bauer and Cathrine Filstad's work on organisational socialisation, Cato Wadel's literature on learning organisations, and Edgar H. Schein's theories on organisational culture. Additional literature includes fields such as physical presence and autonomy as these are factors that are relevant for organisational socialisation at BN. It is not possible to draw final, general conclusions from such a small sample, but many findings point to trends that are specific to this organisation and for organisations in general. The analysis and results following the empirical data collection point at different approaches ii and needs for the onboarding. Our findings indicate that BN could benefit from enhanced learning from the problem owners when deciding on future strategies and processes for onboarding. The managers value their autonomy and the ability to adjust processes to the local needs. Even though each new employee, manager, team, and organisation have their own characteristics, the basis of an onboarding process is to facilitate social safety and establish solid connections. We would argue that BN could benefit from emphasising individual needs and expectations from the new employees. As we approach organisational socialisation as a learning process happening between the actors, establishing a common basis through role clearance and clarifications of expectations is essential. The findings also show that formalised actions such as sponsor or mentorships and trainee programs are elements of onboarding that could benefit from being formalised processes. These are also increasingly important with less physical presence. The responsibility for socialisation lies between the actors as competent individuals, and the core of the socialisation happens through communication and mutual adjustments

Organisasjonssosialisering: En kvalitativ studie av samspillet mellom deltakerne i prosessene rundt organisasjonssosialisering i Bane NOR

Formålet med denne masteroppgaven er å undersøke uformelle og relasjonelle organisatoriske sosialiseringsprosesser, samt ansvaret og forventninger til de ulike aktørene som er involvert. Rolleklarhet, sosial integrasjon, mestring og kunnskap om kulturen oppnås gjennom uformelle praksiser slik som mellommenneskelige relasjoner (Bauer, 2010). Oppgaven er skrevet for Bane NOR (BN). I tider hvor onboardingsprosesser blir digitalisert, er det verdifullt å undersøke hvordan benytte seg av slike ressurser i en mer og mer fragmentert verden. Færre fysiske møter påvirker læringsprosessene for nyansatte. Organisasjoner burde forstå samspillet mellom aktørene som er en del av onboardingsprosesser. Gjennom problemstillingen Hvordan kan forutsetningene for en organisatorisk sosialiseringsprosess hos Bane NOR forbedres ved å ha en eksplisitt og proaktiv tilnærming til oppgaven? vil denne oppgaven bidra til å fremheve viktigheten av dette. Med en utforskende og deskriptiv tilnærming til problemstillingen, er studiet er basert på en kvalitativ metodikk. Datainnsamlingen ble utført ved å intervjue ni informanter som representerer de ulike aktørene som vi studerte, som er den nyansatte, lederen med ansvar for onboardingen og Human Resources (HR). I tillegg har vi samlet inn innsikt fra dokumenter og andre ansatte for å avdekke generelle hensyn knyttet til problemstillingen. Denne studien er basert på et humanistisk menneskesyn, der vi ser på ansatte som sosiale ressurser, i stand til å skape et positivt resultat for alle. Litteratur innenfor feltet viser at et godt grunnlag for onboarding inkluderer et samspill mellom nyansattes egenskaper, atferd og organisatorisk innsats (Bauer & Erdogan, 2011). Oppgaven er basert på Talya N. Bauer og Cathrine Filstads arbeid om organisasjonssosialisering, Cato Wadels litteratur om lærende organisasjoner, og Edgar H. Scheins teorier om organisasjonskultur. Tilleggslitteratur inkluderer felt som fysisk tilstedeværelse og autonomi da dette er faktorer som er relevante for den organisatoriske sosialiseringen i BN. Det vil ikke være mulig å trekke endelige konklusjoner fra et så lite utvalg, men det er mange funn som peker på trender som er spesifikke for denne organisasjonen og organisasjoner generelt. Analysen og resultatene som er basert på den empiriske datainnsamlingen peker på flere aspekter og behov som er viktige for onboardingen. Våre funn indikerer at BN kan med fordel dra nytte av økt læring fra eierne av problemene før de utvikler fremtidige strategier og processer for onboardingen. Lederne verdsetter deres autonomi og muligheten til å tilpasse prosessene til lokale behov. Selv om hver nyansatt, leder, team og organisasjon har sine egne egenskaper, er grunnlaget for en onboardingsprosess å legge til rette for sosial trygghet og etablere solide forbindelser. Vi vil hevde at BN med fordel kan legge vekt på individuelle behov og forventninger fra den nyansatte. Da vi forholder oss til organisasjonssosialisering som en læringsprosess som skjer mellom aktørene, er det viktig å etablere et felles grunnlag gjennom rolle- og forventningsavklaringer. Funnene viser også at formaliserte tiltak som bruk av sponsor, mentor og traineeprogrammer er elementer innen onboarding som bør være sentraliserte prosesser. Disse er i økt grad viktige med mindre fysisk tilstedeværelse. Ansvaret for sosialisering ligger mellom aktørene som kompetente individer og kjernen i sosialiseringen skjer gjennom kommunikasjon og gjensidige tilpasninger.The purpose of this thesis is to research the informal and relational organisational socialisation processes and the responsibilities and needs of the different actors involved. Role clarity, social integration, self-efficacy, and knowledge of culture are achieved through informal practices such as interpersonal relationships (Bauer, 2010). The thesis is conducted in collaboration with Bane NOR (BN). In times when onboarding processes are being digitised, it is valuable to investigate how to utilise such resources in an increasingly fragmented world. Remote work and less physical interaction affect the learning process for new employees. Organisations should understand the interplay between the actors that are a part of an onboarding process. Through the statement How can the conditions for an organisational socialisation process be improved at Bane NOR by taking an explicit and proactive approach to the task? this thesis will contribute to emphasise the importance of such. With an exploratory and descriptive approach to the issue, the study is based on a qualitative methodology. Data collection was conducted by interviewing nine informants that represent the different actors that we were studying, which are the new employee, the manager responsible for the onboarding, and the Human Resources (HR). Additionally, we gathered insights from documents and other employees to uncover general considerations linked to the issue. This study is based on a humanistic view of humanity where we view employees as social resources, capable of creating a positive outcome for all. Literature within the field shows that a solid basis for onboarding practices includes an interplay between new employee characteristics, behaviours, and organisational efforts (Bauer & Erdogan, 2011). The thesis is based on Talya N. Bauer and Cathrine Filstad's work on organisational socialisation, Cato Wadel's literature on learning organisations, and Edgar H. Schein's theories on organisational culture. Additional literature includes fields such as physical presence and autonomy as these are factors that are relevant for organisational socialisation at BN. It is not possible to draw final, general conclusions from such a small sample, but many findings point to trends that are specific to this organisation and for organisations in general. The analysis and results following the empirical data collection point at different approaches and needs for the onboarding. Our findings indicate that BN could benefit from enhanced learning from the problem owners when deciding on future strategies and processes for onboarding. The managers value their autonomy and the ability to adjust processes to the local needs. Even though each new employee, manager, team, and organisation have their own characteristics, the basis of an onboarding process is to facilitate social safety and establish solid connections. We would argue that BN could benefit from emphasising individual needs and expectations from the new employees. As we approach organisational socialisation as a learning process happening between the actors, establishing a common basis through role clearance and clarifications of expectations is essential. The findings also show that formalised actions such as sponsor or mentorships and trainee programs are elements of onboarding that could benefit from being formalised processes. These are also increasingly important with less physical presence. The responsibility for socialisation lies between the actors as competent individuals, and the core of the socialisation happens through communication and mutual adjustments

Probleemsed retseptid, mille alusel ravimi väljastamine apteegist nõuab konsultatsiooni ravimi ordineerijaga Eesti, Norra ja Rootsi võrdlusuuringu põhjal

Uuringu eesmärgiks oli võrrelda probleemsete retseptide esinemissagedust ja sisu Eestis, Norras ning Rootsis. Retsept on probleemne, kui proviisor peab enne ravimi väljastamist apteegist pöörduma ravimi ordineerija poole, samas saab apteeker paljud formaalsed probleemid lahendada iseseisvalt või koostöös patsiendiga. Vaatlusuuring toimus 2006.–2007. a ja selles osales 4 apteeki Eestist, 9 apteeki Norrast ja 6 apteeki Rootsist. Probleemseid retsepte esines enim Eestis, järgnesid Norra ja Rootsi. Formaalsed probleemid olid enim levinud Eestis, ravimi annuse, tugevuse ja ravimivormiga eksiti enam Eestis ja Rootsis. Rootsis oli 28,6%-l ja Norras 25,1%-l juhtudest probleemiks puudulik info ravimi annustamise ning manustamise kohta. Probleemsete retseptide suurem esinemine Eestis oli peamiselt seotud käsitsi kirjutatud retseptide suure osakaaluga. Elektrooniliste retseptide kasutuselevõtu korral võivad ilmneda aga uut tüüpi sisulised vead. Eesti Arst 2010; 89(1):5−1

Situated with Infrastructures: Interactivity and Entanglement in Sensor Data Interpretation

This paper elaborates on situatedness as an empirical phenomenon in computer-mediated settings. It is based on studies of petroleum engineers and how they work with digital sensor data. We show how their work practices are born out of a history of constitutive entanglement with specific types of sensors, the data they produce, and the information systems that process them. This entanglement arises from interaction between humans, technology, and the oil reservoir and is a fundamental aspect of the situations in which interpretative work occurs. We empirically show how different sensors in the petroleum production systems produce data in interaction with their surroundings, and that these data are creatively “stretched” to represent subsurface phenomena. When groups of engineers collaborate remotely with colleagues to make sense of problematic data, entanglement with specific II’s is an important aspect of situatedness. The situationally particular in these settings is not as much a matter of locations as of histories of interaction with specific technologies. The notion of situatedness has been pivotal in stressing the importance of the particular circumstances in which work is performed. It has throughout its history been a counterweight to rationalistic accounts of work and the focus on design of standardized work processes. Here we show that patterns of interaction with specific information infrastructures make up a crucial part of situated work and that these may have non-local dimensions