PREPARATION AND CHARACTERIZATION OF COVALENTLY LINKED ENZYME-ANTIBODY CONJUGATES AND THEIR USE IN MEASURING MINUTE QUANTITIES OF PROTEIN ANTIGENS

The discovery and characterization of oncofetal proteins have led to significant advances in early cancer diagnosis and therapeutic monitoring of patients undergoing cancer chemotherapy. These tumor-associated antigens are presently measured by sensitive, specific immunoassay techniques based on the detection of minute amounts of labeled antigen or antibody incorporated into immune complexes, which must be isolated from free antigen and antibody.^ Since there are several disadvantages with using radioisotopes, the most common immunolabel, one major objective was to prepare covalently coupled enzyme-antibody conjugates and evaluate their use as a practical alternative to radiolabeled immune reagents. An improved technique for the production of enzyme-antibody conjugates was developed that involves oxidizing the carbohydrate moieties on a glycoprotein enzyme, then introducing antibody in the presence of polyethylene glycol (PEG). Covalent enzyme-antibody conjugates involving alkaline phosphatase and amyloglucosidase were produced and characterized.^ In order to increase the sensitivity of detecting the amyloglucosidase-antibody conjugate, an enzyme cycling assay was developed that measures glucose, the product of maltose cleavage by amyloglucosidase, in the picomole range. The increased sensitivity obtained by combined usage of the amyloglucosidase-antibody conjugate and enzyme cycling assay was then compared to that of conventional enzyme immunoassay (EIA).^ For immune complex isolation, polystyrene tubes and protein A-bearing Staphylococcus aureus were evaluated as solid phase matrices, upon which antibodies can be immobilized. A sandwich-type EIA, using antibody-coated S. aureus, was developed that measures human albumin (HSA) in the nanogram range. The assay, using an alkaline phosphatase-anti-HSA conjugate, was applied to the determination of HSA in human urine and evaluated extensively for its clinical applicability.^ Finally, in view of the clinical significance of alpha-fetoprotein (AFP) as an oncofetal antigen and the difficulty with its purification for use as an immunogen and assay standard, a chemical purification protocol was developed that resulted in a high yield of immunochemically pure AFP. ^

The Politics of Local Autonomy: Measuring Cantonal (De)Centralisation in Switzerland

In Switzerland, there are 26 systems of cantonal decentralisation because regulating municipal autonomy is an exclusively cantonal competency. Existing measures of local autonomy/cantonal decentralisation are confined to measuring the real or perceived distribution of functions. Alternatively, they weigh expenditures (Dafflon 1992) or tax revenues (Dlabac and Schaub forthcoming) of municipalities against those of the canton. Complementing these indices, this paper additionally measures the politics dimension of cantonal decentralisation. Seven aspects are measured: intra-cantonal regionalism, cumuldesmandats (double tenure of cantonal MP and mayoral office), territorial quotas for legislative and executive elections, direct local representation and lobbying, party decentralisation, the number and size of constituencies, and direct democracy (communal referendum and initiative). This results in a ranking of all 26 cantons as regards the politics of local autonomy within their political systems. The measure will help scholars to test assumptions held for decentralisation in general, be it as a dependent (explaining decentralisation) or as an independent variable (decentralisation—so what?), within but also beyond the Swiss context.

Improved methods for measuring forest landscape structure: LiDAR complements field-based habitat assessment

Conservation and monitoring of forest biodiversity requires reliable information about forest structure and composition at multiple spatial scales. However, detailed data about forest habitat characteristics across large areas are often incomplete due to difficulties associated with field sampling methods. To overcome this limitation we employed a nationally available light detection and ranging (LiDAR) remote sensing dataset to develop variables describing forest landscape structure across a large environmental gradient in Switzerland. Using a model species indicative of structurally rich mountain forests (hazel grouse Bonasa bonasia), we tested the potential of such variables to predict species occurrence and evaluated the additional benefit of LiDAR data when used in combination with traditional, sample plot-based field variables. We calibrated boosted regression trees (BRT) models for both variable sets separately and in combination, and compared the models’ accuracies. While both field-based and LiDAR models performed well, combining the two data sources improved the accuracy of the species’ habitat model. The variables retained from the two datasets held different types of information: field variables mostly quantified food resources and cover in the field and shrub layer, LiDAR variables characterized heterogeneity of vegetation structure which correlated with field variables describing the understory and ground vegetation. When combined with data on forest vegetation composition from field surveys, LiDAR provides valuable complementary information for encompassing species niches more comprehensively. Thus, LiDAR bridges the gap between precise, locally restricted field-data and coarse digital land cover information by reliably identifying habitat structure and quality across large areas.

Measuring depression with a well-being index: Further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression

BACKGROUND: In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS: The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD: Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS: In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION: Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.