Sustainable Employability of People with Limited Capability for Work: The Participatory Development and Validation of a Questionnaire.

PURPOSE: Understanding sustainable employability (SE) of people with limited capability for work (LCW) due to physical or mental disability is crucial for the sustainable participation of this target group. Therefore, adequate measurement instruments for SE are needed. This study aims to validate a questionnaire to measure SE among people with LCW using a participatory approach, including person-job fit (PJ fit) and work-related sense of coherence (Work-SoC). METHODS: Existing scales for the main concepts were tested and adapted for face validity via cognitive interviews (n = 6), with the involvement of a co-researcher with LCW in the research team. Next, the questionnaire was administered among people with LCW (n = 248) to assess its factor structure (Confirmatory Factor Analysis) and reliability (Cronbach's alpha). RESULTS: Analysis of the cognitive interviews identified problems with clarity and readability of items, instructions and response categories of used (existing) scales. The main adjustments concerned the shortening of text length, the usage of familiar language and examples, and the addition of an introduction game. Most of the adapted SE indicator scales showed an overall good fit and acceptable-to-good internal reliability. The overall SE model had an overall good fit, and excluding 'internal employability' further improved this fit. PJ fit and Work-SoC had an acceptable/good model fit and internal consistency. CONCLUSION: The participatory validation process resulted in a validated and comprehensive questionnaire to measure SE, PJ fit and Work-SoC among people with LCW, which enables research into the development of their SE. This questionnaire can be utilised to contribute to a more inclusive labour market.

Value of the Dutch Holstein Friesian germplasm collection to increase genetic variability and improve genetic merit.

National gene bank collections for Holstein Friesian (HF) dairy cattle were set up in the 1990s. In this study, we assessed the value of bulls from the Dutch HF germplasm collection, also known as cryobank bulls, to increase genetic variability and improve genetic merit in the current bull population (bulls born in 2010-2015). Genetic variability was defined as 1 minus the mean genomic similarity (SIMSNP) or as 1 minus the mean pedigree-based kinship (fPED). Genetic merit was defined as the mean estimated breeding value for the total merit index or for 1 of 3 subindices (yield, fertility, and udder health). Using optimal contribution selection, we minimized relatedness (maximized variability) or maximized genetic merit at restricted levels of relatedness. We compared breeding schemes with only bulls from 2010 to 2015 with schemes in which cryobank bulls were also included. When we minimized relatedness, inclusion of genotyped cryobank bulls decreased mean SIMSNP by 0.7% and inclusion of both genotyped and nongenotyped cryobank bulls decreased mean fPED by 2.6% (in absolute terms). When we maximized merit at restricted levels of relatedness, inclusion of cryobank bulls provided additional merit at any level of mean SIMSNP or mean fPED except for the total merit index at high levels of mean SIMSNP. Additional merit from cryobank bulls depended on (1) the relative emphasis on genetic variability and (2) the selection criterion. Additional merit was higher when more emphasis was put on genetic variability. For fertility, for example, it was 1.74 SD at a mean SIMSNP restriction of 64.5% and 0.37 SD at a mean SIMSNP restriction of 67.5%. Additional merit was low to nonexistent for the total merit index and higher for the subindices, especially for fertility. At a mean SIMSNP of 64.5%, for example, it was 0.60 SD for the total merit index and 1.74 SD for fertility. In conclusion, Dutch HF cryobank bulls can be used to increase genetic variability and improve genetic merit in the current population, although their value is very limited when selecting for the current total merit index. Anticipating changes in the breeding goal in the future, the germplasm collection is a valuable resource for commercial breeding populations.

Perception of livestock ecosystem services in grazing areas.

This study investigates how the ecosystem services (ES) linked to livestock grazing are perceived across countries. A total of 82 case studies collected from 42 countries via survey (53.7% cases from Europe and 46.3% from outside of Europe) have been analysed through a multivariate approach. In all, 18 non-provisioning ES were considered. Overall, the reported impacts of livestock grazing on the different ES were much more positive than negative. Notably, a large proportion of respondents reported either positive or very positive impacts for some cultural ES, namely cultural, historic and natural heritage (84%), knowledge systems and educational values (77%), landscape values (74%), and for some supporting and regulating ES, namely habitat provision (66%), nutrient cycling (65%), and bush encroachment/fire control (66%). Based on multiple regression analysis, geographic origin, stakeholder type and species category, as well as protection status of the grazing area, had significant effects on the perception of the impacts. Respondents reported those impacts as more positive in Europe, in protected areas and where several species were present in the grazing area. A significantly larger proportion of respondents reported recognition of ES provided by the grazing livestock population in European countries (40.9%) compared with non-European countries (23.7%). Based on the survey responses it appears that in non-European countries absence of formal recognition, especially by policy makers, is a major challenge for the continued provision of ES in grazing systems. In Europe, where such recognition is already often included in legislation, the long-term sustainability of related policies and incentives to provide such services is viewed as a major issue by the respondents.

Beyond Parasitism: Hepatic Lesions in Stranded Harbor Porpoises (Phocoena phocoena) Without Trematode (Campula oblonga) Infections.

The liver can be an indicator of the health of an individual or of a group, which can be especially important to identify agents that can cause disease in multiple species. To better characterize hepatic lesions in stranded harbor porpoises (Phocoena phocoena), we analyzed the livers from 39 porpoises that stranded along the Dutch coast between December 2008 and December 2012. The animals were selected because they had either gross or histologic liver lesions with minimal autolysis and no evidence of trematode (Campula oblonga) infection. The most common finding was a chronic hepatitis (22/39, 56.4%) that was often associated with significant disease reported in another organ system (18/22, 81.8%), of which 14 had chronic systemic disease. One case of chronic hepatitis was so severe as to mimic lymphoma, which could only be differentiated with immunohistochemistry. The other common lesions were lipidosis (11/39, 28.2%) and acute hepatitis (6/39, 15.4%), often in combination with mild chronic changes. Overall, although there were no consistent trends in etiology for the hepatic lesions, lipidosis was associated with starvation (8/11, 72.7%) and acute disease, and acute hepatitis was associated with bacterial infections and sepsis (6/6, 100%).

Is dolphin morbillivirus virulent for white-beaked dolphins (Lagenorhynchus albirostris)?

The virulence of morbilliviruses for toothed whales (odontocetes) appears to differ according to host species. In 4 species of odontocetes, morbilliviruses are highly virulent, causing large-scale epizootics with high mortality. In 8 other species of odontocetes, including white-beaked dolphins (Lagenorhynchus albirostris), morbilliviruses have been found as an incidental infection. In these species, the virulence of morbilliviruses is not clear. Therefore, the admission of 2 white-beaked dolphins with morbillivirus infection into a rehabilitation center provided a unique opportunity to investigate the virulence of morbillivirus in this species. By phylogenetic analysis, the morbilliviruses in both animals were identified as a dolphin morbillivirus (DMV) most closely related to that detected in a white-beaked dolphin in Germany in 2007. Both animals were examined clinically and pathologically. Case No. 1 had a chronic neural DMV infection, characterized by polioencephalitis in the cerebrum and morbillivirus antigen expression limited to neurons and glial cells. Surprisingly, no nervous signs were observed in this animal during the 6 months before death. Case No. 2 had a subacute systemic DMV infection, characterized by interstitial pneumonia, leucopenia, lymphoid depletion, and DMV antigen expression in mononuclear cells and syncytia in the lung and in mononuclear cells in multiple lymphoid organs. Cause of death was not attributed to DMV infection in either animal. DMV was not detected in 2 contemporaneously stranded white-beaked dolphins. Stranding rate did not increase in the region. These results suggest that DMV is not highly virulent for white-beaked dolphins.

Selection of SNP from 50K and 777K arrays to predict breed of origin in cattle.

Reliable breed assignment can be performed with SNP. Currently, high density SNP chips are available with large numbers of SNP from which the most informative SNP can be selected for breed assignment. Several methods have been published to select the most informative SNP to distinguish among breeds. In this study, we evaluated Delta, Wright's FST, and Weir and Cockerham's FST, and extended these methods by adding a rule to avoid selection of sets of SNP in high linkage disequilibrium (LD) providing the same information. The SNP that had a r2 value>0.3 with any of the SNP already selected were discarded. The different selection methods were evaluated for both the 50K SNP and 777K Bovine BeadChip. Animals from 4 cattle breeds (989 Holstein Friesian, 97 Groningen White headed, 137 Meuse-Rhine-Yssel, and 64 Dutch Friesian) were genotyped. After editing 30,447 and 452,525 SNP were available for the 50K and 777K SNP chip, respectively. All selection methods showed that only a small set of SNP is needed to differentiate among the 4 Dutch cattle breeds, whereas comparison of the selection methods showed only small differences. In general, the 777K performed marginally better than the 50K BeadChip, especially at higher confidence thresholds. The rule to avoid selection of SNP in high LD reduced the required number of SNP to achieve correct breed assignment. The Global Weir and Cockerham's FST performed marginally better than other selection methods. There was little overlap in the SNP selected from the 2 BeadChips, whereas the number of SNP selected was about the same.

The use of SWOT analysis to explore and prioritize conservation and development strategies for local cattle breeds.

SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis is a tool widely used to help in decision making in complex systems. It suits to exploring the issues and measures related to the conservation and development of local breeds, as it allows the integration of many driving factors influencing breed dynamics. We developed a quantified SWOT method as a decision-making tool for identification and ranking of conservation and development strategies of local breeds, and applied it to a set of 13 cattle breeds of six European countries. The method has four steps: definition of the system, identification and grouping of the driving factors, quantification of the importance of driving factors and identification and prioritization of the strategies. The factors were determined following a multi-stakeholder approach and grouped with a three-level structure. Animal genetic resources expert groups ranked the factors, and a quantification process was implemented to identify and prioritize strategies. The proposed SWOT methodology allows analyzing the dynamics of local cattle breeds in a structured and systematic way. It is a flexible tool developed to assist different stakeholders in defining the strategies and actions. The quantification process allows the comparison of the driving factors and the prioritization of the strategies for the conservation and development of local cattle breeds. We identified 99 factors across the breeds. Although the situation is very heterogeneous, the future of these breeds may be promising. The most important strengths and weaknesses were related to production systems and farmers. The most important opportunities were found in marketing new products, whereas the most relevant threats were found in selling the current products. The across-breed strategies utility decreased as they gained specificity. Therefore, the strategies at European level should focus on general aspects and be flexible enough to be adapted to the country and breed specificities.

Farmer's views and values to focus on cattle conservation policies: the case of eight European countries.

Our aim was to identify elements useful in designing policies and programmes for conservation of farm animal genetic resources, taking as case study a group of European local cattle breeds. We first investigated the implications of differences among countries in the policies and programmes to be developed. Secondly, we analysed key elements common to countries, which may affect local breed viability. We used the herd size trend expected by the farmer in the near future as an indicator of breed viability. Fifteen breeds, for a total of 355 farms, were surveyed. To take into account the multiple factors influencing breeds' demographic trends, the questionnaire included economical, technical and social aspects. Among the major differences across countries was the perception of the farmer on the value attributed to the local breed by society. Concerning the elements common to countries and their association to breed viability, the greater the collaboration among farmers and the stakeholders' appreciation as perceived by the farmer, the greater the viability of the farm. An opposite trend was observed for the age of the farmer. Older farmers generally planned to soon cease farming or decrease herd size, whereas young farmers planned to increase the size of their herds. Implications of including these elements in conservation policies are discussed.

Developing a typology for local cattle breed farmers in Europe.

Recognizing cultural diversity among local breed farmers is crucial for the successful development and implementation of farm animal genetic resources FAnGr conservation policies and programmes. In this study based on survey data collected in the EUropean REgional CAttle breeds project from six European countries, a typology of local breed farmers was designed and profiles for each of the farmer types were developed to assist these policy needs. Three main farmer types were constructed: production-oriented, product and service-oriented and hobby-oriented farmers. In addition, seven subtypes were characterized under the main types: sustainable producers, opportunists, multi-users, brand makers, traditionalists, pragmatists and newcomers. These types have many similarities to the 'productivist', 'multifunctional' and 'post-productivist' farmer types. The typology not only reveals the high level of diversity among local cattle breed farmers in Europe, which presents an opportunity for the in situ conservation of animal genetic resources, but also a challenge for policy to meet the differing requirements of the farmer types.

How developments in cryobiology, reproductive technologies and conservation genomics could shape gene banking strategies for (farm) animals.

Many local breeds are currently at risk because of replacement by a limited number of specialized commercial breeds. Concurrently, for many breeds, allelic diversity within breeds declines because of inbreeding. Gene banking of germplasm may serve to secure the breeds and the alleles for any future use, for instance to recover a lost breed, to address new breeding goals, to support breeding schemes in small populations to minimize inbreeding, and for conservation genetics and genomics research. Developments in cryobiology and reproductive technology have generated several possibilities for preserving germplasm in farm animals. Furthermore, in some mammalian and bird species, gene banking of material is difficult or impossible, requiring development of new alternative methods or improvement of existing methods. Depending on the species, there are interesting possibilities or research developments in the use of epididymal spermatozoa, oocytes and embryos, ovarian and testicular tissue, primordial germ cells, and somatic cells for the conservation of genetic diversity in farm- and other animal species. Rapid developments in genomics research also provide new opportunities to optimize conservation and sampling strategies and to characterize genome-wide genetic variation. With regard to gene banks for farm animals, collaboration between European countries is being developed through a number of organizations, aimed at sharing knowledge and expertise between national programmes. It would be useful to explore further collaboration between countries, within the framework of a European gene banking strategy that should minimize costs of conservation and maximize opportunities for exploitation and sustainable use of genetic diversity.

Ex situ conservation of Holstein-Friesian cattle: comparing the Dutch, French, and US germplasm collections.

Holstein-Friesian (HF) gene bank collections were established in France, the Netherlands, and the United States to conserve genetic diversity for this breed. Genetic diversity of HF collections within and between countries was assessed and compared with active male HF populations in each country by using pedigree data. Measures of genetic diversity such as probability of gene origin inbreeding and kinship were calculated. The cryobanks have captured substantial amounts of genetic diversity for the HF compared with the current populations. A substantial part of the US, French, and Dutch collections seems to be genetically similar. On the other hand, the US collection in particular represents an interesting reservoir of HF genes of the past. Gene banks can play an important role in conserving genetic diversity within livestock breeds over time, and may support industry in the future when needed.

Short communication: milk fat composition of 4 cattle breeds in the Netherlands.

Milk fatty acid (FA) composition was compared among 4 cattle breeds in the Netherlands: Dutch Friesian (DF; 47 animals/3 farms), Meuse-Rhine-Yssel (MRY; 52/3), Groningen White Headed (GWH; 45/3), and Jersey (JER; 46/3). Each cow was sampled once between December 2008 and March 2009 during the indoor housing season, and samples were analyzed using gas chromatography. Significant breed differences were found for all traits including fat and protein contents, 13 major individual FA, 9 groups of FA, and 5 indices. The saturated fatty acid proportion, which is supposed to be unfavorable for human health, was smaller for GWH (68.9%) compared with DF (74.1%), MRY (72.3%), and JER (74.3%) breeds. The proportion of conjugated linoleic acid and the unsaturation index, which are associated positively with human health, were both highest for GWH. Differences in milk fat composition can be used in strategies to breed for milk with a FA profile more favorable for human health. Our results support the relevance of safeguarding the local Dutch breeds.

Animal genetic resources conservation in the Netherlands and Europe: poultry perspective.

Increased global use of highly productive breeds of farm animals has been coupled to loss of genetic diversity in most species. In European countries, various governmental, non-governmental, and private organizations try to preserve genetic diversity of livestock in situ (e.g., by stimulating the use of indigenous, rare breeds by farmers; in nature reserves; or in noncommercial farms). In the case of poultry, maintaining in situ populations of the noncommercial (fancy) breeds largely relies on hobby farmers. In addition to in situ conservation, gene banks are being established for ex situ conservation. In at least 2 countries, France and The Netherlands, there are limited collections of frozen semen of rare poultry breeds. Since 2003, the CGN has started with a more systematic effort to collect, freeze, and store semen of indigenous Dutch poultry breeds. At present, the CGN gene bank contains semen of 11 Dutch rare poultry breeds. Also, CGN has performed research on the methodology for cryopreservation of fowl semen. This recent work was focused on finding a suitable replacement for glycerol, which is contraceptive in the hen, as a cryoprotectant. For reasons of hygiene and sample identification, we favored straw freezing, as opposed to the highly effective pellet freezing method. A significant interaction was found between cooling rate and cryoprotectant concentration. Best post-thaw sperm quality was obtained when combining 0.6 mol of dimethylacetamide/L with a cooling rate of +/- 200 degrees C/min. Inseminations twice per week with 0.3 billion sperm per insemination resulted in 97 and 88% fertilized eggs with fresh and frozen semen, respectively. In 2005, CGN has used this straw freezing method to extend the collection of poultry semen in the Dutch gene bank.

The safety and tolerability of candesartan cilexetil in CHF.

The management of congestive heart failure (CHF) continues to represent a major therapeutic challenge. The primary goal of any treatment is the improvement of symptoms with a reduction in CHF related morbidity and a neutral or beneficial effect on mortality. The number of hospitalisations is considered an important measure of morbidity and quality-of-life in these patients. This pooled safety analysis was performed on adverse event data from five placebo-controlled studies involving a total of 1893 patients, 1287 of whom received candesartan cilexetil and 606 of whom received placebo. These were the only placebo-controlled phase II and III studies of candesartan safety available at the time of the analysis, and investigated the efficacy and safety of candesartan cilexetil in patients with CHF. None was designed as an endpoint trial. A blinded, independent review of all adverse event data was performed to assess all-cause mortality and unexpected deaths, and hospitalisations for acute deterioration of CHF, chronic progression of CHF, other intercurrent events, or accidental injury/attempted suicide. The descriptive analysis included crude and cumulative incidence rates for mortality and cardiac and non-cardiac morbidity using the Kaplan-Meier method and the log-rank test. The sample population was predominantly (approximately two thirds) male, with a median age of 61 years (range: 20-89 years). The median age for women in the sample population was 66 years (range: 26-86 years). Patients received candesartan cilexetil, 2-32 mg, over a median period of 84 days (range: 1-418 days), or placebo over a median period of 85 days (range: 1-398 days). The results demonstrated a clinically non-significant trend for all relevant events (deaths and hospitalisations, whether related to CHF or not) to occur less frequently in patients receiving candesartan cilexetil than in patients receiving placebo (deaths - candesartan cilexetil: 1.6%, placebo: 1.8%; hospitalisations - candesartan cilexetil: 7.2%, placebo: 10.9%). There was a significant treatment difference in CHF hospitalisations (candesartan cilexetil: 3.0% vs. placebo: 5.6%). The time to event analysis revealed that significantly fewer hospitalisations due to CHF occurred in the group receiving candesartan cilexetil than in the group receiving placebo. This treatment difference persisted throughout therapy (log-rank test; p < 0.028). These results show the safety of candesartan cilexetil, compared with placebo, in the treatment of patients with CHF.

Isolated limb perfusion with tumour necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study.

This open, multicentre, randomized phase II trial was conducted to determine the effect of isolated limb perfusion (ILP) with tumour necrosis factor-alpha (TNFalpha) in combination with melphalan with or without interferon-gamma (IFNgamma) in patients with in-transit metastases of melanoma of the limbs (MD Anderson stage IIIA or IIIAB, AJCC stage III). The 64 patients included were randomized to receive either a two- drug regimen consisting of TNFalpha and melphalan (TM-ILP) or a three-drug regimen consisting of TNFalpha, melphalan and INFgamma (TIM-ILP). Patients randomized to receive IFNgamma were pretreated for 2 days before the ILP with once daily 0.2 mg IFNgamma subcutaneously and also received the same amount of IFNgamma during ILP. A total of 47 complete responses (73%) were reported, 22 (69%) of which occurred in the TM-ILP group and 25 (78%) in the TIM-ILP group; the difference was not significant. The 14 partial responses (22%) were split evenly between the treatment groups. In the TM-ILP group, two cases of stable disease and one case of progressive disease were reported. The overall response rate (complete plus partial responses) was 100% in the TIM-ILP group and 91% in the TM-ILP group, yielding an overall response of 95% for this study. In the historical control data, where 103 patients had received melphalan alone (M-ILP), there were 54 records of complete responses (52%) and 80 of complete or partial responses (78%). The median survival time estimated by the Kaplan-Meier method was 819 days for the TM-ILP group, > 705 days for the TIM-ILP group and 873 days for the combined study population; estimates for time to local progression or recurrence were 327 days, in excess of 498 days and 405 days, respectively. The corresponding figure for the historical controls was 338 days. These data suggest that TNFalpha associated with melphalan may be superior to melphalan alone for ILP.

Karsch-Neugebauer syndrome in two sibs with unaffected parents.

We report on 2 sisters with Karsch-Neugebauer syndrome comprising split foot and split hand anomalies in association with congenital nystagmus. These sisters share a nearly identical phenotype with the 8 previously reported instances of this disorder. Although genetic heterogeneity can not be formally excluded, most evidence suggests that Karsch-Neugebauer syndrome is an autosomal dominant disorder. If so, then this report of 2 affected sibs born to healthy parents is the second instance of apparent gonadal mosaicism in this disorder. The apparent high frequency of gonadal mosaicism is important to recognize in counseling families with this disorder.

Genetic counseling in limb reduction defects.

During several years experience in a multidisciplinary out-patient clinic for children with congenital hand malformations a systematic approach was devised to arrive at an accurate diagnosis and recurrence risk in patients with congenital limb reduction defects. Classification and diagnostic work-up was done according to a protocol, derived from data in the literature and from our own experience. This protocol is described for the different types of congenital upper limb reduction defects.

Does cantharides blister fluid provide access to the peripheral compartment?

The pharmacokinetics of bendroflumethiazide (BFT) was investigated following the oral administration of 10 mg to 3 healthy volunteers. Each subject participated twice in the study. BFT was determined in plasma and cantharides blister fluid from 1/2 to 30 h post administration. Blister fluid was obtained from blisters 10-22 h old. Plasma levels were fitted to a tri-exponential equation and the concentration of the drug in the peripheral compartment was calculated from the microscopic rate constants. In 5 of 6 cases investigated, cantharides blister fluid levels paralleled the concentration of the drug in the peripheral compartment. The mean blister fluid levels exceeded the calculated concentration in Compartment 2 1.46 fold. In one case, the blister fluid level paralleled the plasma level. This subject clearly differed from the others as more than 10 h were required for blister formation in her. The results suggest that following the administration of BFT, cantharides blister fluid behaves as part of the peripheral compartment. The possible value of studying blister fluid levels in pharmacokinetic investigations is discussed.