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Objective: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, β-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated with severe conditions in homozygote or compound heterozygote forms are identified yearly. Thus far, approximately 60 patients and 800 healthy sickle cell (HbS) carriers are reported each year among 180,000 newborns. Results are sent to the general practitioner with the recommendation to inform and diagnose both parents of the healthy carriers to exclude genetic risk, while patients and their parents are referred directly to a pediatrician. This study was performed to determine how often parents of identified carriers and affected newborns are seen in genetic centers for counseling. Methods: In this retrospective study, we collected anonymized data from 7 of the 8 Dutch clinical genetic centers from January 1, 2007, until December 31, 2010. Results: After an initial general increase in total counseling intakes, a decline was noticed in the third year, while the requests for prenatal diagnoses remained relatively stable. In 2007 and 2013, genetic counselors were asked for self-reported knowledge. They found hemoglobinopathy counseling complex, but by 2013, they indicated they had acquired sufficient knowledge on most hemoglobinopathy aspects. Conclusion: We could not observe a significant increase in genetic counseling for hemoglobinopathy after its introduction into newborn screening. Although 120 HbS carriers and 60 patients are expected to be born from couples at risk annually, only 33 at risk couples out of 540 families of diagnosed newborns received optimal care and information at a genetics center in 4 years.

Colonisation of maize roots by arbuscular mycorrhizal (AM) fungi leads to the accumulation of apocarotenoids (cyclohexenone and mycorradicin derivatives). Other root apocarotenoids (strigolactones) are involved in signalling during early steps of the AM symbiosis but also in stimulation of germination of parasitic plant seeds. Both apocarotenoid classes are predicted to originate from cleavage of a carotenoid substrate by a carotenoid cleavage dioxygenase (CCD), but the precursors and cleavage enzymes are unknown. A Zea mays CCD (ZmCCD1) was cloned by RT-PCR and characterised by expression in carotenoid accumulating E. coli strains and analysis of cleavage products using GC—MS. ZmCCD1 efficiently cleaves carotenoids at the 9, 10 position and displays 78% amino acid identity to Arabidopsis thaliana CCD1 having similar properties. ZmCCD1 transcript levels were shown to be elevated upon root colonisation by AM fungi. Mycorrhization led to a decrease in seed germination of the parasitic plant Striga hermonthica as examined in a bioassay. ZmCCD1 is proposed to be involved in cyclohexenone and mycorradicin formation in mycorrhizal maize roots but not in strigolactone formation.

Background An unclassified variant (UV) in exon 1 of the MLH1 gene, c.112A > C, p.Asn38His, was found in six families who meet diagnostic criteria for Lynch syndrome. The pathogenicity of this variant was unknown. We aim to elucidate the pathogenicity of this MLH1 variant in order to counsel these families adequately and to enable predictive testing in healthy at-risk relatives. Methods We studied clinical data, microsatellite instability and immunohistochemical staining of MMR proteins, and performed genealogy, haplotype analysis and DNA testing of control samples. Results The UV showed co-segregation with the disease in all families. All investigated tumors showed a microsatellite instable pattern. Immunohistochemical data were variable among tested tumors. Three families had a common ancestor and all families originated from the same geographical area in The Netherlands. Haplotype analysis showed a common haplotype in all six families. Conclusions We conclude that the MLH1 variant is a pathogenic mutation and genealogy and haplotype analysis results strongly suggest that it is a Dutch founder mutation. Our findings imply that predictive testing can be offered to healthy family members. The immunohistochemical data of MMR protein expression show that interpreting these results in case of a missense mutation should be done with caution.

This paper examines how firms succeed to leverage supplier involvement in product development. The paper extends earlier work on managing supplier involvement by providing an integrated analysis of results, processes and conditions both at the level of individual development projects and the overall firm. Following a multiple-case study approach with theoretical sampling, the study is carried out by examining eight projects in which four manufacturers from different industries involve multiple suppliers. The findings suggest that successful supplier involvement is dependent on the coordinated design, execution and evaluation of strategic, long-term processes and operational, short-term management processes and the presence of enabling factors such as a cross-functional oriented organization. The required intensity of these processes and enablers depends on contingencies such as firm size and environmental uncertainty. In contrast with previous research, we find no indications that managing supplier involvement requires a different approach in highly innovative projects compared to less innovative projects.

Existing studies of supplier involvement in new product development have mainly focused on project-related short-term processes and success-factors. This study validates and extends an existing exploratory framework, which comprises both long-term strategic processes and short-term operational processes that are related to supplier involvement. The empirical validation is based on a multiple-case study of supplier collaborations at a manufacturer in the copier and printer industry. The analysis of eight cases of supplier involvement reveals that the results of supplier-manufacturer collaborations and the associated issues and problems can best be explained by the patterns in the extent to which the manufacturer manages supplier involvement in the short-term ànd the long-term. We find that our initial framework is helpful in understanding why certain collaborations are not effectively managed, yet conclude that the existing analytical distinction between four different management areas does not sufficiently reflect empirical reality. This leads us to reconceptualize and further detail the framework. Instead of four managerial areas, we propose to distinguish between the Strategic Management arena and the Operational Management arena. The Strategic Management arena contains processes that together provide long-term, strategic direction and operational support for project teams adopting supplier involvement. These processes also contribute to building up a supplier base that can meet current and future technology and capability needs. The Operational Management arena contains processes that are aimed at planning, managing and evaluating the actual collaborations in a specific development project. The results of this study suggest that success of involving suppliers in product development is reflected by the firm's ability to capture both short-term and long-term benefits. If companies spend most of their time on operational management in development projects, they will fail to use the 'leverage' effect of planning and preparing such involvement through strategic management activities. Also, they will not be sufficiently able to capture possible long-term technology and learning benefits that may spin off from individual projects. Long-term collaboration benefits can only be captured if a company can build long-term relationships with key suppliers, where it builds learning routines and ensures that the capability sets of both parties are aligned and remain useful for future joint projects.