Need for recovery and different types of early labour force exit: a prospective cohort study among older workers.

PURPOSE: This study examines the relationship between need for recovery (NFR) and labour force exit (LFE) among older workers. Different types of LFE (early retirement, work disability and unemployment) are considered, and the role of potential confounding and modifying factors, including the availability of early LFE schemes, is examined. Also, associations between NFR and the intention and ability to prolong one's working life, which are known determinants of LFE, are assessed. METHODS: A subsample of older workers from the Maastricht Cohort Study was examined (n = 2312). The relationship between NFR and LFE was investigated by means of Cox regression analyses. Logistic regression analyses were performed to investigate cross-sectional associations between NFR and the intention and ability to prolong working life. RESULTS: Elevated NFR was associated with a higher risk of overall LFE during a 4-year follow-up period (HR 1.39, 95% CI 1.09-1.78), and specifically with a higher risk of leaving the labour force through early retirement and work disability. When early retirement schemes were available, strong and significant associations between NFR and LFE were observed (HR 2.79, 95% CI 1.29-6.02), whereas no significant associations were found when such schemes were unavailable. Older workers with a higher NFR also had earlier retirement intentions and lower self-assessed abilities (both physical and mental) to prolong their working life until the mandatory retirement age. CONCLUSIONS: Because this study shows that NFR is a precursor of LFE among older workers, monitoring NFR is important for timely interventions aimed at reducing NFR to facilitate extended labour participation.

The impact of depression and diabetes mellitus on older workers' functioning.

OBJECTIVE: Using the International Classification of Functioning, Disability and Health as a framework, this study investigates the impact of depression and diabetes mellitus on older workers' functioning (problems with concentration, physical functioning, need for recovery and work and social participation restrictions). The study focuses on how these chronic conditions, in their interaction with the work context, affect older workers' functioning, which may be an important precursor of early retirement. METHODS: Older workers (≥ 45years) with depression (n=127) or diabetes mellitus (n=107) enrolled in the prospective Maastricht Cohort Study (MCS) were followed between October 2008 and October 2012. Linear, logistic and Cox regression analyses were performed to investigate the effect of these health conditions on workers' functioning compared to a reference group of older workers without a chronic condition (n=1612). The interaction with participants' working conditions (psychological job demands, decision latitude and strenuous work) was also analysed. RESULTS: Compared to the reference group, depression and diabetes mellitus were (over time) positively related with need for recovery caseness and restrictions in social participation but not with restrictions in work participation. Depression was positively related with concentration problems and need for recovery, whereas diabetes mellitus was negatively related with physical functioning. Finally, the relationship between functioning and depression and diabetes mellitus depends on working conditions. CONCLUSION: Older workers with depression or diabetes mellitus are vulnerable to losses in specific domains of functioning. The impact on functioning varies across working conditions, providing insight for disease-tailored preventive measures.

Need for recovery across work careers: the impact of work, health and personal characteristics.

PURPOSE: Employees experiencing a high need for recovery (NFR) are at risk of long-term adverse effects in both their health and labour participation. So far, the determinants of NFR across age categories remain unknown. The aim of this study is to investigate the determinants of the NFR among employees in three age categories (30-44, 45-54 and 55-65 years), for men and women separately. METHODS: The study was based on data from the prospective Maastricht Cohort Study. Wave T3 (May 1999) was chosen as article baseline (n = 7,900). The follow-up period of 20 months included five follow-up waves. Cox regression analyses were performed to investigate the determinants, which originated from the work environment, health and lifestyle and personal domain of employees, of NFR across age categories over time. RESULTS: Cross-sectional results demonstrated substantial differences in mean scores and proportion of cases of NFR across age categories. Longitudinal analyses demonstrated risk factors in the multifactorial aetiology of NFR that played a role in all age categories, but also showed several age-specific risk factors, e.g. low decision latitude appeared to be a risk factor only in the oldest age category. CONCLUSIONS: Although selection effects may have occurred, this study shows that the risk factors for a high NFR were different among the age categories. To prevent and reduce a high NFR among employees, it is important to develop preventive measures that target age-specific risk factors.

Evaluation of a newly developed HIV antigen test.

A new monoclonal antibody-based enzyme immunoassay (Innogenetics) for the detection and quantification of p24 core antigens of HIV-1 (group M and group O) and of HIV-2 was evaluated on 2745 serum samples and 18 culture supernatants and compared with a reference (Coulter) HIV-1 p24 antigen assay. Positive results were confirmed by neutralization with the reagents of the respective tests. As demonstrated by dilution series of HIV cocultures, the new test recognizes p24 antigen of the most common HIV genetic subtypes, including group O and HIV-2. Titres ranged from 729 to 531441. Therefore p24 antigen assay is but very weakly reactive with HIV-2 (titres from 9 to 81). The new test is considerably more sensitive than the reference. In a population of 365 follow-up samples from 86 different patients, representing all stages of infection, the new test detected p24 antigen at least once in 52% (45/86) of these patients, whereas the reference was positive in 31% (27/86). The newly designed test detected antigen in 40% (145/365) of the samples, while the reference was positive in 21% (75/365). In a group of PCR and/or culture positive neonates, 33% (9/27) of the samples were positive with the new test versus 18% (5/27) with the reference. The specificity of the new test, as determined on 2,000 blood donor samples, was 99.65% (initially), 99.80% (after repetition), and 100% (with neutralization). The reference scored 99.95%, 100%, and 100%, respectively. In 300 seronegative samples from persons at risk, the initial specificity of the new test was 98.67% (the reference, 99.00%). With neutralization, both assays were 100% specific.

Sandwich enzyme-linked immunosorbent assay compared with Pastorex latex agglutination test for diagnosing invasive aspergillosis in immunocompromised patients.

The performance of a direct sandwich enzyme-linked immunosorbent assay (ELISA) for detecting Aspergillus galactomannan was compared with that of the Pastorex Aspergillus antigen latex agglutination (LA) test by using 532 serum samples from 61 patients at risk for invasive aspergillosis. The ELISA gave positive results earlier in the course of infection than did the LA test. A sensitivity of 70% and a specificity of 86% were obtained for the LA test and corresponding values of 90 and 84% were obtained for the ELISA when a series of serum samples was employed.

A new sensitive sandwich enzyme-linked immunosorbent assay to detect galactofuran in patients with invasive aspergillosis.

A double-direct sandwich enzyme-linked immunosorbent assay that uses a rat anti-galactomannan monoclonal antibody as the acceptor and detector antibody was designed. This immunoassay, which detects less than 1 ng of galactomannan per ml, was assessed in a retrospective study with samples from patients with invasive aspergillosis. Serum is more appropriate than urine for use in the search for circulating galactomannan. Antigenemia does not have a transient character. Galactomannan can be detected at least 39 days before the death of the patients.

[Specific antigens and antibodies in invasive aspergillosis]. / Antigènes et anticorps spécifiques dans l'aspergillose invasive.

Early diagnosis of invasive aspergillosis is of utmost importance but difficult to achieve. Serological methods were developed mainly because all the other diagnostic approaches had major drawbacks. The detection of antibodies against Aspergillus antigens provided little interesting information, since anti-Aspergillus antibodies were commonly found in healthy people, while, on the other hand, immunocompromised patients often failed to raise antibodies. Several groups of investigators showed that the detection in serum or urine by RIA or ELISA of Aspergillus antigens, was a highly specific indication of invasive disease. The sensitivities of the techniques, however, were moderate, partially due to the low antigen concentrations and the transient character of antigenemia. The only commercially available test is a latex agglutination test detecting 15 ng/ml galactomannan. It has a high specificity but reported sensitivities varied between 42% and 94.7%. Results with an experimental double-sandwich ELISA detecting about 1 ng/ml galactomannan suggest that the improvement of detection limit also greatly increases the clinical value of the test: patients become and remain positive 2 to 10 weeks earlier. If these results are confirmed, antigen detection could become a essential element in the management of an immunocompromised patient population.

Detection of galactomannan and the 18 kDa antigen from Aspergillus fumigatus in serum and urine from cattle with systemic aspergillosis.

Serum and urine samples from cattle with experimental and spontaneous systemic mycotic infections were tested for the presence of galactomannan and the 18 kDa antigen from Aspergillus fumigatus by an inhibition ELISA and immunoblotting, respectively. High levels of galactomannan (approximately 80 ng/ml.) were detected in serum from two of three calves experimentally infected with A. fumigatus. In two out of three cows with spontaneous acquired aspergillosis a similar amount of galactomannan was detected. Galactomannan was not found in serum samples of 20 cows which aborted due to either experimental or spontaneous placental aspergillosis. Twenty-four of forty urine samples from normal cattle reacted positively in the ELISA, consequently, the assay was not applicable on bovine urine. The 18 kDa antigen from A. fumigatus was detected in the urine from one calf out of three calves experimentally infected with aspergillosis and in the urine from one cow with spontaneous aspergillosis. It is concluded that detection of galactomannan in serum and the 18 kDa antigen in urine may be used as an aid for the diagnosis of disseminated bovine aspergillosis with the exception of placental and probably gastrointestinal localization.

Enzyme immunohistochemistry with mono- and polyclonal antibodies in the pathological diagnosis of systemic bovine mycoses.

To improve the immunohistopathological diagnosis of systemic bovine mycoses, we have evaluated the utility of antifungal polyclonal and monoclonal antibodies, and peroxidase and alkaline phosphatase staining techniques. A rabbit polyclonal antibody to mannan from Candida albicans was specific for candidosis. The diagnosis of aspergillosis was accomplished using a rat monoclonal antibody to the galactofuran side chains of Aspergillus galactomannan. A murine monoclonal antibody reacting with weakly Con-A binding 41 and 46 kDa somatic antigens from Absidia corymbifera was used for immunostaining of zygomycetic hyphae. Peroxidase antiperoxidase (PAP) and alkaline phosphatase antialkaline phosphatase (APAAP) complexes were visualized using aminoethylcarbazole and fast red substrates. A green staining of PAP reactions with dioctyl sulfosuccinate sodium and 3,3',5,5'-tetramethylbenzidine (DONS/TMB) was effective for the demonstration of fungi in dual and triple infections. Tissue sections of experimentally infected mice were used to determine the sensitivity and specificity of the antibodies. Tissues obtained from 161 bovine mycotic lesions previously studied by indirect immunofluorescence staining were further evaluated using the three antibodies. In all of 45 lesions solely affected by aspergillosis and in three solely affected by candidosis the diagnoses were confirmed by the new evaluation. In 85 of 96 cases of single infections with zygomycetes the diagnosis was confirmed, while none of the antibodies reacted with fungal elements in the remaining 11 lesions. Aspergillus hyphae were detected in all three lesions with dual aspergillosis and zygomycosis, whereas zygomycetic material was confirmed in only two of these cases. A mixed infection of candidosis and zygomycosis in a lymph node was confirmed too. In 13 cases in which a diagnosis had not hitherto been obtained, aspergillosis and zygomycosis were recorded each in three cases.

Retrospective evaluation of two latex agglutination tests for detection of circulating antigens during invasive candidosis.

Two latex agglutination tests for the detection of Candida antigens, Pastorex Candida (Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France) and Cand-Tec (Ramco Laboratories, Inc., Houston, Tex.), were applied to 79 serum samples from 19 patients who were retrospectively selected on the basis of mycological and clinical evidence of C. albicans infection and the availability of serial serum samples taken near the date of a positive culture. The specificity in 60 control individuals was 100% for Pastorex and 98.3% for Cand-Tec. The tests scored positive for 10 (52.6%) and 9 (47.4%) patients, respectively. Pastorex detected antigen in only 3 of 12 patients (25%) with positive antibody detection tests, but was positive for all 7 patients (100%) who produced no or a low antibody response, suggesting that the test performs better in the absence of antibodies. However, the sensitivity of Pastorex also increased with the number of samples available per patient, which was lower for high-antibody-responder patients (2.8 versus 5.7). If the patients who provided only one or two serum samples were eliminated, the sensitivity of Pastorex rose to 76.9%. For the Cand-Tec, the sensitivity was not related to the presence of antibodies, nor was it related to the number of samples per patient. The observed antigenemia was transient with both Pastorex and Cand-Tec. Only 12.5% of the positive reactions occurred on the same serum sample, confirming that the two tests react with different antigens. A positive antigen test preceded other diagnostic indications for 6 of 10 Pastorex-positive patients and 5 of 9 Cand-Tec-positive patients.

Immunodiagnosis of nocardiosis.

A specific immunodominant 54-kDa antigen was purified from a culture filtrate of Nocardia asteroides by immunoaffinity chromatography. The chromatography column was prepared with immunoglobulin G obtained from sera from patients with lepromatous leprosy. Unbound solutes consisted of specific, partially purified N. asteroides antigens, primarily a 54-kDa band, accompanied by two others of 31 and 62 kDa. The Western blot (immunoblot) technique was applied to detecting the immunologic response to nocardiae in the serum of nocardiosis patients. Each of the serum samples from immunosuppressed or immunocompetent patients infected with N. asteroides reacted with the 54-kDa band, and two reacted with the 31- and 62-kDa bands. There was no reaction to either the 54- or the 31-kDa antigen with all serum samples obtained from patients with tuberculosis, except for one, with all serum samples obtained from patients with leprosy, or with all sera obtained from healthy controls. The partially purified 54-kDa antigen, specific for N. asteroides, was used as the immunogen to generate monoclonal antibodies (mAbs) and two mAbs were selected. As determined by Western blot, both mAbs reacted with the 54-kDa band. Using indirect immunofluorescence or enzyme immunoassay with whole N. asteroides micro-organisms, the mAbs did not react with N. asteroides cells. No cross-reactivity with mycobacterial antigens, either culture-filtrate antigens or tuberculin, was exhibited with any of the two mAbs. These mAbs are candidates to be used for the development of a sensitive and specific diagnostic test for nocardiosis.

Immunohistochemical identification of Penicillium marneffei by monoclonal antibody.

We present an experimental study on the immunohistochemical identification of Penicillium marneffei in paraffin-embedded, formalin-fixed tissue. The monoclonal antibody EB-A1 detects a specific galactomannan that appears to have at least one epitope identical in P. marneffei and Aspergillus sp. This immunohistochemical approach could be useful in the diagnosis of a rare diseae, penicilliosis marneffei, which proves to be difficult to identify by conventional microscopy.

Rat monoclonal antibodies against Aspergillus galactomannan.

Monoclonal antibodies (MAbs) against Aspergillus fumigatus galactomannan were produced in rats. Seven of them, EB-A1 through EB-A7, were characterized in more detail. They were all immunoglobulin M antibodies, reacting in an indirect enzyme-linked immunosorbent assay with purified A. fumigatus galactomannan, with avidity constants of between 2 x 10(9) and 5 x 10(9)/M. Enzyme-linked immunosorbent assay inhibition experiments with modified galactomannan and synthetic oligomers of beta (1----5)galactofuranose demonstrated that the MAbs bound to an epitope located on the beta(1----5)galactofuranose-containing side chains of the galactomannan molecule. An identical or similar epitope also seemed to be present in other fungi. Immunofluorescence and immunoelectron microscopy experiments with EB-A2 revealed the presence of the antigen in the fungal wall and inside the cell. Immunoblotting experiments demonstrated that the epitope recognized by the MAbs was a common oligosaccharide moiety of a wide range of intracellular and extracellular glycoproteins in A. fumigatus. The characteristics of the MAbs justify their use in the diagnosis of invasive aspergillosis by antigen detection.

Monoclonal antibodies to a specific 54-kilodalton antigen of Nocardia spp.

Two monoclonal antibodies (MAbs) of the immunoglobulin G2A isotype, reacting with a Nocardia-specific 54-kDa antigen, were generated. As determined by Western blot (immunoblot), both MAbs reacted only with the 54-kDa band. As determined by indirect immunofluorescence or enzyme immunoassay with whole microorganisms, the MAbs did not react with Nocardia cells. One of the MAbs showed weak cross-reactivity with mycobacterial antigens, while the other showed no cross-reactivity.

Immunohistochemical expression of galactomannan in the cytoplasm of phagocytic cells during invasive aspergillosis.

The monoclonal antibody EB-A1 to galactomannan is apparently specific for detecting Aspergillus species and Penicillium marneffei in formalin-fixed, paraffin-embedded tissues. It reveals hyphae, remnants of filaments, and organisms in the cytoplasm of some phagocytic cells.

Detection of circulating galactomannan by Pastorex Aspergillus in experimental invasive aspergillosis.

The performance of Pastorex Aspergillus, a new latex agglutination test for the detection of circulating galactomannan in the serum of patients with invasive aspergillosis, was evaluated in a blind trial in standardized guinea-pig models of invasive aspergillosis and other invasive mycoses. In these animal models, the invasive nature of the fungal infection was confirmed by re-isolation of the etiologic agent from the organs of every animal. Ninety-two plasma samples from 42 animals with invasive aspergillosis were submitted to the test. In 41 of these animals, at least one plasma sample was positive with the latex test (sensitivity 97.6%), titers ranging from 1/1 to 1/512. In general, antigen titers increased as a function of time, reaching the highest values shortly before death. Guinea-pigs infected with Penicillium marneffei also yielded positive agglutination reactions but antigen titers were lower (maximal titer 1/8). Plasma samples from animals with invasive candidosis (23), disseminated trichophytosis (11) and cryptococcosis (23) were all negative with the latex test. In 80 guinea-pigs without fungal infection, 3 false positive results (titers 1/1) were observed, which means a specificity of 96.2% in this control group.

[Immunohistochemical identification of Aspergillus by monoclonal antibody EB-A1]. / Identification immunohistochimique des Aspergillus par l'anticorps monoclonal EB-A1.

We have developed a new monoclonal antibody EB-A1 that recognizes Aspergillus sp. by immunoassay and in formalin fixed tissues. The sensitivity of this antibody is excellent and its specificity appears correct as many human tissues and several fungi other than Aspergillus sp. are not revealed.

Concanavalin A reactivity of vitellogenin and yolk proteins of the threespined stickleback Gasterosteus aculeatus (Teleostei).

1. Concanavalin A (con A) reactive proteins have been detected in the plasma and ovaries of the oestradiol treated Gasterosteus aculeatus. 2. Concanavalin A-horseradish peroxidase (HRP) technique applied on nitrocellulose membranes reveals that vitellogenin (Vg) is the only mannose and glucose rich glycoprotein present in the plasma of oestradiol treated sticklebacks. Stickleback Vg can be purified by con A-Sepharose chromatography. 3. Con A reactivity in the ovary changes in the course of development of the oocytes. First, the yolk vesicles, which are synthesized by the oocyte itself, become con A positive. Later, the yolk granules, which contain vitellogenin synthesized in the liver and taken up from the plasma, show a clear affinity for con A. Con A staining disappears when mannopyranoside is added. 4. No con A staining is found in the periodic acid/Schiff staining chorion.