Penetrance and predictive value of genetic screening in acute porphyria

Objective: Penetrance, predictive value and female patients' perspectives on genetic testing were evaluated among Finnish patients with acute porphyria. We conducted a retrospective study to evaluate prognosis among at-risk female family members depending on the primary method of diagnosis. Methods: The penetrance was calculated among 23 genetically heterogeneous families selected from the Finnish porphyria registry (n = 515, AIP 333; VP 182). We included kindreds with >= 9 patients in a family (range 9-23 patients, total 216 AIP; 129 VP). In 2015, the registry included 164 living female subjects between 14 and 85 years of age. A questionnaire was sent to 143 women, of whom 107 (75%, AIP 67; VP 40) replied. Female at-risk relatives (AIP 54; VP 30) were divided into two groups based on the primary method of diagnosis: mutation analysis (Group A, n = 40) or biochemical analysis (Group B, n = 44). Results: Mean penetrance for all acute symptoms was 35% among AIP and 40% among VP families. In both study groups, the penetrance was higher among female (AIP 50%; VP 44%) than male patients (AIP 17%; VP 33%). Penetrance for hospitalized attacks was 30% among AIP families (range 10-80%, for women 41%) and 25% in VP (range 0-50%, for women 27%) demonstrating wide variations among families even with the similar genotype. Acute porphyria was diagnosed at the median age of 26 years (range 0-76 years) among female patients, commonly after the onset of acute symptoms. Diagnostic delay was an average of 7.4 years (range 1-30 years). Acute symptoms occurred at the median age of 24 years (range 10-57 years) and the first hospitalization at the median age of 26.5 years (range 15-57 years). At the onset of symptoms, 38% of the women were Conclusions: Among female at-risk relatives the annual risk for hospitalization due to an acute attack is <1% and for acute symptoms <2% during the fertile years. Genetic testing of relatives diminishes the risk of acute attacks. Diagnosis before symptom onset is key for subjects to remain asymptomatic during follow-up, and genetic screening should be done earlier than currently.Peer reviewe

Ujous lasten kuvakirjoissa

Tiivistelmä. Tämän tutkimuksen tavoitteena on selvittää, miten ujoutta käsitellään lapsille suunnatuissa 2000-luvulla ilmestyneissä kuvakirjoissa. Ujous on pysyvä temperamenttipiirre, joka kuitenkin tässä ajassa ja kulttuurissa nähdään negatiivisena ominaisuutena. Lasten ujous herättää myös kasvattajissa huolestuneita kysymyksiä. Koska kuvakirjat ovat tärkeä osa lasten kulttuuria ja ne muokkaavat lasten maailmankuvaa, halusin tutkia, millaisena ilmiönä ujous kuvakirjoissa lapsille esitetään. Ujoutta lasten kuvakirjoissa ei ole aikaisemmin tutkittu. Tutkimuskysymykseni ovat seuraavat: Millaista määritelmää kuvakirjat ujoudesta tuottavat? Miten kuvakirjojen ujouden kuvaus vastaa yhteiskunnan suhtautumista ujouteen? Tutkimusaineistonani on kahdeksan 2000-luvulla julkaistua ujoudesta kertovaa kuvakirjaa. Tutkimusmenetelmänäni on sisällönanalyysi, jonka avulla kirjallisessa muodossa olevaa aineistoa voi luokitella sisällön perusteella eri luokkiin. Tutkimuksessani ilmenee, että ujous on tarkastelemissani kuvakirjoissa esitetty uusissa sosiaalisissa tilanteissa ilmenevänä ensireaktiona, joka saa ujon hahmon vetäytymään. Kuvakirjoissa ujous lisäksi estää ujoa hahmoa saavuttamasta päämääräänsä, jolloin ujon hahmon on kirjassa ylitettävä ujoutensa. Ystävyyttä käsittelevissä kuvakirjoissa ujous on ujojen hahmojen näkökulmasta negatiivinen ominaisuus, joka johtaa sosiaalisiin ongelmiin. Tämä vastaa yhteiskunnan suhtautumista ujouteen. Kuvakirjat saattavat tarjota samaistumisen kokemuksia ujoille lapsille, jos lapset kokevat ujouden estävän heitä toimimasta toivomallaan tavalla. Kuvakirjat saattavat myös lisätä ei-ujojen lasten empatiaa ujoutta kohtaan. Toisaalta voi miettiä, ovatko kuvakirjoissa esitetyt ujouden ylittämiseen käytetyt keinot toimivia ujojen lasten näkökulmasta

The role of polaronic states in the enhancement of CO oxidation by single-atom Pt/CeO2

Single Atom Catalysts (SACs) have shown that the miniaturization of the active site implies new phenomena like dynamic charge transfer between isolated metal atoms and the oxide. To obtain direct proof of this character is challenging, as many experimental techniques provide averaged properties or have limitations with poorly conductive materials, leaving kinetic measurements from catalytic testing as the only reliable reference. Here we present an integrated Density Functional Theory-Microkinetic model including ground and metastable states to address the reactivity of Pt1/CeO2 for CO oxidation. Our results agree with experimentally available kinetic data in the literature and show that CO oxidation activity of Pt1/CeO2 is tunable via the electronic properties of the support. Particularly, samples with higher n-doping via oxygen depletion should be better in CO oxidation, as they help maintain the active state Pt0 of the catalyst. This provides an alternative strategy for tuning the performance of low-temperature oxidations in single-atom catalysts via charge transfer control

Rationality as the Rule of Reason

The demands of rationality are linked both to our subjective normative perspective (given that rationality is a person-level concept) and to objective reasons or favoring relations (given that rationality is non-contingently authoritative for us). In this paper, I propose a new way of reconciling the tension between these two aspects: roughly, what rationality requires of us is having the attitudes that correspond to our take on reasons in the light of our evidence, but only if it is competent. I show how this view can account for structural rationality on the assumption that intentions and beliefs as such involve competent perceptions of downstream reasons, and explore various implications of the account

Prevalence of obesity and disturbances in glucose homeostasis in HIV-infected subjects and general population - missed diagnoses of diabetes?

Objectives Comparative data on glucose disorders using fasting blood samples between people living with HIV (PLWH) and the general population are lacking. The objective of this study was to compare the prevalence and risk factors of obesity and disturbances in glucose homeostasis between PLWH treated with modern antiretroviral therapy and the general population. Methods Adjusted prevalence of obesity, features of insulin resistance (triglyceride:high-density lipoprotein cholesterol ratio and alanine aminotransferase), impaired fasting glucose (IFG), diabetes mellitus (DM) and combined dysglycaemia (presence of IFG or DM) were determined using fasting blood samples among 1041 PLWH and 7047 subjects representing the general population. Results People living with HIV had a lower prevalence of obesity [18.2%, 95% confidence interval (CI): 15.1-21.2 vs. 23.9%, 95% CI: 22.4-25.4], but a higher prevalence of insulin resistance and IFG (20.0%, 95% CI: 16.6-23.4 vs. 9.8%, 95% CI: 8.7-10.8) than the general population. Fasting glucose concentration was higher, but glycated haemoglobin (HbA1c) was lower, among PLWH. Prevalence of dysglycaemia for a given body mass index (BMI) was higher in PLWH than in the general population. The prevalence of DM did not differ between PLWH (13.2%, 95% CI: 10.2-15.9) and the general population (14.5%, 95% CI: 13.6-15.4). Conclusions The prevalence of obesity was lower, but the risk of dysglycaemia for a given BMI was significantly higher, among PLWH, highlighting the importance of prevention and treatment of obesity among HIV-infected subjects. Regardless of the increased prevalence of insulin resistance and IFG, DM was surprisingly not more common among PLWH, raising concern about the under-diagnosis of DM, possibly due to low sensitivity of HbA1c in this patient population.Peer reviewe

Condition Controlling and Monitoring of Indoor Swimming Pools

VTT has executed a lot of research work concerning the usage, functionality and refurbishment of indoor swimming pools and spas lately. This work includes for instance detailed condition surveys, energy audits, cost analysis and maintenance planning tools. The prevailing conditions make special demands for planning, constructing, repairing and maintaining the indoor swimming pools. Main topics are usually connected with shortening of the service lives of the building parts and technical installations and the indoor air quality. Also the yearly running costs can be remarkable high. VTT has created the technical risk map for indoor swimming pool repairs. This risk map presents the most significant factors that must be taken into account in order to repair facilities successfully. Due to optimizing the operation and maintenance VTT has developed operation and maintenance manual software that is specially targeted for indoor swimming facilities. This paper presents the technical risk map, the condition survey procedure, the energy saving methods and the maintenance record book for indoor swimming facilities to secure the success of a refurbishment project