Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with prenatally diagnosed kidney anomalies.

Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next-generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in-house-designed kidney-gene panel. In families where candidate variants were not identified, whole-exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney-gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney-gene panel and additional variants were identified. Next-generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT-ROBO signaling is implicated in human bilateral kidney agenesis.

Dry chemistry instruments in primary care. I. Operating conditions and financial considerations.

The objectives of this study were to describe the operating conditions of dry chemistry instruments in primary care, as well as to elucidate financial aspects in general practice fee-for-service settings. We used questionnaires mailed to all users of the two most used dry chemistry instruments in Norway, as well as to a 14% random sample of Norwegian GPs. The overall response rate was 79%. The mean number of dry chemistry analyses varied considerably between individual users, but in general a substantial number of analyses were carried out. Even though most analyses on the instruments' repertoire were available in all user groups, a total of 13 additional constituents were suggested to be included in the repertoire. In occupational health care most results were ready when the client was present; this was not the case in general practice. The instruments were more profitable when more constituents were analysed per sample, although profitability varied substantially in the period studied (1986-1989). A discrete time history event analysis revealed that net profit earned, lower instrument price, available information about the technology and being in solo practice significantly influenced the decision to buy an instrument in fee-for-service practices.

Technological diffusion in primary health care.

The paper contains a theoretical and empirical analysis of the driving forces behind the diffusion of dry chemical laboratory equipment in Norwegian primary health care. The empirical analysis is embedded in a theoretical model of a dynamic investment problem focusing on heterogeneity in the potential adopters' profit functions. The empirical analysis indicates that most adopters are too late in adopting the new technology. A logit analysis of the diffusion process lends some support to the notion that profit function heterogeneity influences the diffusion process. An offspin of the empirical analysis is information on the reimbursement system, indicating that this system does not promote efficient resource allocation in the sector.