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PubMed1999

Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31.

Recent studies have shown that, in addition to its role as an adhesion receptor, platelet endothelial cell adhesion molecule 1/CD31 becomes phosphorylated on tyrosine residues Y663 and Y686 and associates with protein tyrosine phosphatases SHP-1 and SHP-2. In this study, we screened for additional proteins which associate with phosphorylated platelet endothelial cell adhesion molecule 1, using surface plasmon resonance. We found that, besides SHP-1 and SHP-2, platelet endothelial cell adhesion molecule 1 binds the cytoplasmic signalling proteins SHIP and PLC-gamma1 via their Src homology 2 domains. Using two phosphopeptides, NSDVQpY663TEVQV and DTETVpY686SEVRK, we demonstrate differential binding of SHP-1, SHP-2, SHIP and PLC-gamma1. All four cytoplasmic signalling proteins directly associate with cellular platelet endothelial cell adhesion molecule 1, immunoprecipitated from pervanadate-stimulated THP-1 cells. These results suggest that overlapping immunoreceptor tyrosine-based inhibition motif/immunoreceptor tyrosine-based activation motif-like motifs within platelet endothelial cell adhesion molecule 1 mediate differential interactions between the Src homology 2 containing signalling proteins SHP-1, SHP-2, SHIP and PLC-gamma1.

Amino Acid Sequence↗
PubMed2003

Loss of a single allele of SHIP exacerbates the immunopathology of Pten heterozygous mice.

Phosphatidylinositol 3-kinase (PI3K) has emerged as a critical component of multiple immune system intracellular signalling pathways. The levels and relative ratios of PI3K products, phosphatidylinositol (3,4) bisphosphate (PI(3,4)P(2)) and phosphatidylinositol (3,4,5) trisphosphate (PIP(3)), are regulated by inositol phosphatases such as Pten and SHIP. Interestingly, mice heterozygous for Pten, a 3'-inositol phosphatase, develop a progressive lymphoproliferative syndrome with autoimmune features. Given the importance of PIP(3) species in regulating immune responses, we hypothesized that heterozygosity for the 5'-inositol phosphatase SHIP might exacerbate the autoimmune phenotype of Pten(+/-) mice. In keeping with this, mice heterozygous for both Pten and SHIP developed lymphoproliferation, hypergammaglobulinaemia, autoantibody titres and renal pathology that were more severe than that of Pten(+/-) mice. These results suggest that the relative levels of phosphatidylinositol phosphatases are likely critical to immune system homeostasis and they also highlight the potential for gene dosage effects in regulating susceptibility and/or severity of autoimmunity.

Animals↗
PubMed2002

Stabilized viral nucleic acids in plasma as an alternative shipping method for NAT.

BACKGROUND: Preservation of the integrity of viral nucleic acids in blood specimens during shipping and handling is crucial for NAT and viral load monitoring. An economical and convenient method is described for nucleic acid stabilization by using an RNA stabilizing solution (RNAlater, Ambion) in plasma that is designed for the shipment of samples to tropical countries. STUDY DESIGN AND METHODS: HCV, HIV, and HBV FFP were compared with RNAlater-treated plasma and dried plasma spots (DPSs) after incubation at 37 degrees C, which was chosen as an upper limit of ambient shipping temperature, for up to 28 days. HCV-infected chimpanzee plasma was shipped at either room temperature after RNAlater treatment or as frozen plasma in liquid nitrogen from Liberia to New York City. They were then compared for HCV RNA levels. The nucleic acid stabilities were determined by quantitative PCR by using a molecular beacon assay on a sequence detection system (ABI 7700, PE-Biosystems) and by visualizing the PCR components on an acrylamide gel. RESULTS: Quantitative PCR data showed that a 60:40 or greater ratio of RNAlater:plasma volume successfully stabilized HCV RNA and HIV RNA in plasma for up to 28 days at 37 degrees C. HBV DNA in plasma was stable for up to 14 days at 37 degrees C without any stabilizing solution. DPSs on filter paper stabilized viral nucleic acids, but the recoveries were 3 to 10 times less than those with frozen plasma. The integrity of the 5' UTR region of HCV RNA in RNA later-treated chimpanzee plasma was intact when its PCR component was viewed on an acrylamide gel. CONCLUSION: The DPS method stabilized nucleic acids, at least with the extraction method used, was less sensitive than use of RNAlater, and required tedious manual handling. RNAlater provides a convenient way of stabilizing viral nucleic acid in plasma at ambient temperature during sample transportation.

5' Untranslated Regions↗
PubMed2002

Physical and thermal properties of blood storage bags: implications for shipping frozen components on dry ice.

BACKGROUND: Frozen blood components are shipped on dry ice. The lower temperature (-70 degrees C in contrast to usual storage at -30 degrees C) and shipping conditions may cause a rent in the storage bag, breaking sterility and rendering the unit useless. The rate of loss can reach 50 to 80 percent. To identify those bags with lower probability of breaking during shipment, the thermal and physical properties of blood storage bags were examined. STUDY DESIGN AND METHODS: Blood storage bags were obtained from several manufacturers and were of the following compositions: PVC with citrate, di-2-ethylhexylphthalate (DEHP), or tri-2-ethylhexyl-tri-mellitate (TEHTM) plasticizer; polyolefin (PO); poly(ethylene-co-vinyl acetate) (EVA); or fluorinated polyethylene propylene (FEP). The glass transition temperature (Tg) of each storage bag was determined. Bag thickness and measures of material strength (tensile modulus [MT] and time to achieve 0.5 percent strain [T0.5%]) were evaluated. M(T) and T0.5% measurements were made at 25 and -70 degrees C. Response to applied force at -70 degrees C was measured using an impact testing device and a drop test. RESULTS: The Tg of the bags fell into two groups: 70 to 105 degrees C (PO, FEP) and -50 to -17 degrees C (PVC with plasticizer, EVA). Bag thickness ranged from 0.14 to 0.41 mm. Compared to other materials, the ratios of M(T) and T0.5% for PVC bags were increased (p < or = 0.001) indicating that structural changes for PVC were more pronounced upon cooling from 25 to -70 degrees C. Bags containing EVA were more shock resistant, resulting in the lowest rate of breakage (10% breakage) when compared with PO (60% breakage, p = 0.0573) or PVC (100% breakage, p = 0.0001). CONCLUSIONS: Blood storage bags made of EVA appear better suited for shipping frozen blood components on dry ice and are cost-effective replacements for PVC bags. For the identification of blood storage bags meeting specific storage requirements, physical and thermal analyses of blood storage bags may be useful and remove empiricism from the process.

Blood Preservation↗
PubMed2004

Co-aggregation of FcgammaRII with FcepsilonRI on human mast cells inhibits antigen-induced secretion and involves SHIP-Grb2-Dok complexes.

Signaling through the high affinity IgE receptor FcepsilonRI on human basophils and rodent mast cells is decreased by co-aggregating these receptors to the low affinity IgG receptor FcgammaRII. We used a recently described fusion protein, GE2, which is composed of key portions of the human gamma1 and the human epsilon heavy chains, to dissect the mechanisms that lead to human mast cell and basophil inhibition through co-aggregation of FcgammaRII and FcepsilonRI. Unstimulated human mast cells derived from umbilical cord blood express the immunoreceptor tyrosine-based inhibitory motif-containing receptor FcgammaRII but not FcgammaRI or FcgammaRIII. Interaction of the mast cells with GE2 alone did not cause degranulation. Co-aggregating FcepsilonRI and FcgammaRII with GE2 1) significantly inhibited IgE-mediated histamine release, cytokine production, and Ca(2+) mobilization, 2) reduced the antigen-induced morphological changes associated with mast cell degranulation, 3) reduced the tyrosine phosphorylation of several cellular substrates, and 4) increased the tyrosine phosphorylation of the adapter protein downstream of kinase 1 (p62(dok); Dok), growth factor receptor-bound protein 2 (Grb2), and SH2 domain containing inositol 5-phosphatase (SHIP). Tyrosine phosphorylation of Dok was associated with increased binding to Grb2. Surprisingly, in non-stimulated cells, there were complexes of phosphorylated SHIP-Grb2-Dok that were lost upon IgE receptor activation but retained under conditions of Fcepsilon-Fcgamma co-aggregation. Finally, studies using mast cells from Dok-1 knock-out mice showed that IgE alone triggers degranulation supporting an inhibitory role for Dok degranulation. Our results demonstrate how human FcepsilonRI-mediated responses can be inhibited by co-aggregation with FcgammaRIIB and implicate Dok, SHIP, and Grb2 as key intermediates in regulating antigen-induced mediator release.

Adaptor Proteins, Signal Transducing↗
PubMed2004

SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase.

The Tec family of protein-tyrosine kinases (PTKs), that includes Tec, Itk, Btk, Bmx, and Txk, plays an essential role in phospholipase Cgamma (PLCgamma) activation following antigen receptor stimulation. This function requires activation of phosphatidylinositol 3-kinase (PI 3-kinase), which promotes Tec membrane localization through phosphatidylinositol 3,4,5-trisphosphate (PtdIns 3,4,5-P(3)) generation. The mechanism of negative regulation of Tec family PTKs is poorly understood. In this study, we show that the inositol 5' phosphatases SHIP1 and SHIP2 interact preferentially with Tec, compared with other Tec family members. Four lines of evidence suggest that SHIP phosphatases are negative regulators of Tec. First, SHIP1 and SHIP2 are potent inhibitors of Tec activity. Second, inactivation of the Tec SH3 domain, which is necessary and sufficient for SHIP binding, generates a hyperactive form of Tec. Third, SHIP1 inhibits Tec membrane localization. Finally, constitutively targeting Tec to the membrane relieves SHIP1-mediated inhibition. These data suggest that SHIP phosphatases can interact with and functionally inactivate Tec by de-phosphorylation of local PtdIns 3,4,5-P(3) and inhibition of Tec membrane localization.

Amino Acid Motifs↗
PubMed2006

International shipping of fumonisins from maize extracts on C18 sorbent.

Fumonisins are mycotoxins found in maize. In developing countries, the resources required for analysis are often lacking, and the shipping of maize between countries can be difficult since the importation of plant materials requires permits/inspection to prevent the entry of pests that frequently infest maize. A simple, safe and legal method for shipping maize extracts to the USA was needed to conduct a survey of fumonisins in Central America. The objective was to develop a method for isolating and shipping maize extracts for fumonisin analysis so as to facilitate a survey of fumonisin exposure. The results indicate that fumonisins in acetonitrile:water extracts of maize can be isolated on C18 cartridges, held for at least 3 days at 22 degrees C and then an additional 4 days at 4 degrees C before elution and analysis with no losses. This method allows the importation and analysis of maize samples from foreign locations without complications from international safety concerns.

Carbon↗
PubMed2006

T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2.

Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Modeling ship transportation risk

This article presents results from the Commission of the European Communities (CEC) project "Safety of Shipping in Coastal Waters" (SAFECO). The project was performed by ten European partners during the period 1995-1998. The principal aim of the SAFECO project was to determine the influences that could increase the safety of shipping in coastal waters by analyzing the underlying factors contributing to the marine accident risk level. The work reported here focuses on the Marine Accident Risk Calculation System (MARCS) that was further developed during the SAFECO project. This paper presents the methods used by MARCS, as well as data and results from a "demonstration of concept" case study covering the North Sea area. The estimated accident frequencies (number of accidents per year) were compared with historical accident data, to demonstrate the validity of the modeling approach. Reasonable (within a factor of 5) to good (within a factor of 2) agreement between calculated accident frequencies and observed accident statistics was generally obtained. However, significant discrepancies were identified for some ship types and accident categories. The risk model has particular problems with estimating the accident frequency for drift grounding in general and powered grounding for ferries. It was concluded that these discrepancies are related to uncertainties in several areas, specifically in the risk model algorithms, the traffic data, the error and failure probability data, and the historical accident statistics.

Journal Article↗
PubMed2005

Traumatic work related mortality among seafarers employed in British merchant shipping, 1976-2002.

AIMS: To establish the causes and circumstances of all traumatic work related deaths among seafarers who were employed in British merchant shipping from 1976 to 2002, and to assess whether seafaring is still a hazardous occupation as well as a high risk occupation for suicide. METHODS: A longitudinal study of occupational mortality, based on official mortality files, with a population of 1,136,427 seafarer-years at risk. RESULTS: Of 835 traumatic work related deaths, 564 were caused by accidents, 55 by suicide, 17 by homicide, and 14 by drug or alcohol poisoning. The circumstances in which the other 185 deaths occurred, including 178 seafarers who disappeared at sea or were found drowned, were undetermined. The mortality rate for 530 fatal accidents that occurred at the workplace from 1976 to 2002, 46.6 per 100,000 seafarer-years, was 27.8 times higher than in the general workforce in Great Britain during the same time period. The fatal accident rate declined sharply since the 1970s, but the relative risk of a fatal accident was 16.0 in 1996-2002. There was no reduction in the suicide rate, which was comparable to that in most high risk occupations in Britain, from 1976 to 1995; but a decline since 1995. CONCLUSIONS: Although there was a large decline in the fatal accident rate in British shipping, compared to the general workforce, seafaring has remained a hazardous occupation. Further prevention should focus on improvements in safety awareness among seafarers and shipping companies, reductions in hazardous working practices, and improvements in care for seafarers at risk of suicide.

Accidents, Occupational↗
PubMed1988

Effect of enrofloxacin therapy on shipping fever pneumonia in feedlot cattle.

The effect of enrofloxacin therapy was investigated in 110 male double-muscled cattle weighing 275 +/- 3 kg, during a spontaneous outbreak of shipping fever occurring 11 +/- 2 days after they arrived in the feedlot. Forty-six diseased animals were divided randomly into three groups A, B and C, containing 17, 19 and 10 animals, respectively; the animals in group A were injected intramuscularly once daily for three consecutive days with 2.5 mg/kg of enrofloxacin, those in group B with 5 mg/kg of enrofloxacin and those in group C with 10 mg/kg of oxytetracycline. Clinical, serological, production and respiratory functional observations were recorded. The animals were clinically cured after the three day treatment except for three in group A and two in group C. These five animals made a clinical recovery after a three day booster treatment with a dose of 5 mg/kg enrofloxacin. The changes in respiratory gas exchange values induced by shipping fever were completely reversed 15 days later, suggesting that there had been no irreversible lung damage. The daily weight gains and the arterial blood gas values of the three groups of treated cattle were not significantly different. The high efficacy of the low dosage of enrofloxacin in this clinical syndrome may be explained by its antibacterial activity against Pasteurella species and Mycoplasma species. This field trial supports the in vitro studies which suggested than enrofloxacin is an appropriate therapy in cases of shipping fever.

4-Quinolones↗
PubMed2001

Regional shipping strategy assessment based on installing a refuse-derived-fuel process in a municipal incinerator.

The rising prices of raw materials and the concerns of energy recovery have resulted in an increasing interest in processing the waste streams. In recent years, a number of credible surveys have shown that recycling and waste-to-energy processes appear to work well together. Compatibility exists for several reasons related to economic, environmental, political, and social aspects. However, the regional impacts of installing a centralised refused-derived fuel (RDF) process prior to waste-to-energy facilities remain unclear due to the inherent complexity of solid waste composition, generation rate, energy and material recovery goals, and the existing shipping patterns. This paper illustrates a thorough evaluation for a RDF pilot study from both quantitative and qualitative aspects. Such a process, consisting of the standard unit operations of shredding, magnetic separation, trommel screening, and air classification, might be useful for integrating the recycling and presorting efforts with a large-scale municipal incinerator in a region. A series of sampling and analyses of the waste streams were performed in Taipei County, Taiwan in order to characterise its potentials for recycling. Based on the proper estimation of solid waste generation, the goal programming modelling analysis not only focuses on an evaluation of how the waste inflows with different rates of generation, physical and chemical compositions, and heating values in the service areas can be processed by a centralised RDF facility to meet both the energy recovery and throughput requirements in different municipal incinerators but also indicates the optimal shipping pattern associated with several incinerators due to such an installation in a regional sense. A case study designed to explore the regional impacts on shipping patterns in the southwestern of Taipei County, Taiwan verifies the application potential of such a planning methodology.

Conservation of Natural Resources↗
PubMed1995

Survival of pseudorabies virus on swabs maintained under standard field sample shipping conditions.

Pseudorabies virus survival was compared using three different types of applicator swabs in Eagle's minimum essential medium held under shipping conditions (packed with frozen gel packs) for up to 96 hours. Virus titer decay rates for dacron-tipped applicators were not statistically different from those of controls. Titer decay rates were statistically different from controls for cotton- and calcium alginate-tipped applicators. With the lowest input virus titer, virus was detectable up to 96, 72, or 24 hours after inoculation for dacron-, cotton-, and calcium alginate-tipped applicators, respectively. Dacron-tipped applicators were chosen to evaluate pseudorabies virus survival on tonsil swabs collected from experimentally challenged or contact control pigs to simulate field sampling and shipping conditions. Virus was still detectable in 20 of 24 swab samples after 72 hours in cell culture medium under shipping conditions.

Alginates↗
PubMed2004

Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1.

The Lyn tyrosine kinase plays essential inhibitory signaling roles within hematopoietic cells by recruiting inhibitory phosphatases such as SH2-domain containing phosphatase-1 (SHP-1), SHP-2, and SH2-domain containing 5'-inositol phosphatase (SHIP-1) to the plasma membrane in response to specific stimuli. Lyn-deficient mice display a collection of hematopoietic defects, including autoimmune disease as a result of autoantibody production, and perturbations in myelopoiesis that ultimately lead to splenomegaly and myeloid neoplasia. In this study, we demonstrate that loss of Lyn results in a stem/progenitor cell-intrinsic defect leading to an age-dependent increase in myeloid, erythroid, and primitive hematopoietic progenitor numbers that is independent of autoimmune disease. Despite possessing increased numbers of erythroid progenitors, and a more robust expansion of these cells following phenylhydrazine challenge, Lyn-deficient mice are more severely affected by the chemotherapeutic drug 5-fluorouracil, revealing a greater proportion of cycling progenitors. We also show that mice lacking SHIP-1 have defects in the erythroid and myeloid compartments similar to those in mice lacking Lyn or SHP-1, suggesting an intimate relationship between Lyn, SHP-1, and SHIP-1 in regulating hematopoiesis.

Animals↗
PubMed2004

Optical influence of ship wakes.

The optical variations observed within ship wakes are largely due to the generation of copious amounts of air bubbles in the upper ocean, a fraction of which accumulate as foam at the surface, where they release scavenged surfactants. Field experiments were conducted to test previous theoretical predictions of the variations in optical properties that result from bubble injection in the surface ocean. Variations in remote-sensing reflectance and size distribution of bubbles within the ship-wake zone were determined in three different optical water types: the clear equatorial Pacific Ocean, moderately turbid coastal waters, and very turbid coastal waters, the latter two of which were offshore of New Jersey. Bubbles introduced by moving vessels increased the backscattering in all cases, which in turn enhanced the reflectance over the entire visible and infrared wave bands. The elevated reflectance had different spectral characteristics in the three locations. The color of ship wakes appears greener in the open ocean, whereas little change in color was observed in near-coastal turbid waters, consistent with predictions. Colorless themselves, bubbles increase the reflected radiance and change the color of the ocean in a way that depends on the spectral backscattering and absorption of the undisturbed background waters. For remote observation from aircraft or satellite, the foam and added surfactants further enhance the reflectance to a degree dependent on the illumination and the viewing geometry.

Journal Article↗
PubMed1986

The effects of two shipping treatments on the carcass characteristics of bulls implanted with zeranol and unimplanted steers.

A total of 144 male crossbred calves were allocated to four management treatments (bulls; steers; bulls implanted with zeranol at 100 d of age and re-implanted at 69, 93 and 56 d thereafter; bulls implanted with zeranol at 168 d of age and re-implanted at 93 and 56 d thereafter), and two pre-slaughter shipping treatments (minimum pre-slaughter stress with cattle shipped and slaughtered within 4 h of leaving the feedlot pen; moderate pre-slaughter stress with cattle mixed, trucked 160 km and slaughtered up to 24 h of leaving the feedlot pen) in a 4 X 2 factorial arrangement. Management treatment had no significant effect on carcass pH (45 min), carcass muscle temperature (45 min), or peak shear-force of cooked longissimus muscle. Steers had significantly lower dressing percentage, warm-carcass weight, hide weight and carcass-lean content, but higher marbling score, fat thickness and intramuscular-fat content than all treatments with bulls. Minimum pre-slaughter stress resulted in significantly lower dressing percentage, warm-carcass weight, and carcass pH (45 min), but generally had no effect on carcass tissue-yield measurements compared with the moderate stress treatment. Implanted bulls produced carcasses with significantly darker meat, higher 24-h pH and lower meat expressible juice than bulls and castrates for the moderate pre-slaughter stress treatment. These results provide evidence that zeranol implantation in bulls had a minor influence on carcass characteristics, and did not reduce the incidence of dark-cutting carcasses in young bulls subjected to moderate pre-slaughter shipping stress.

Animals↗
PubMed2004

A multivariate analysis of factors associated with differential disease and nonbattle injury and morbidity aboard ships of the U.S. Naval 5th Fleet during peacetime deployment.

Disease nonbattle injury (DNBI) surveillance is a critical component of U.S. military force health protection and has been aggressively implemented by the U.S. Central Command. This study presents a multivariate analysis of factors associated with DNBI incidence rates as well as a description of morbidity measures associated with DNBI from U.S. Navy ships deployed to the Middle East from October 2000 through September 2001. Weekly DNBI reports (N = 331) from a total of 44 individual units representing six different classes of U.S. Navy ships were included in the analysis. There were statistically significant differences in summary and categorical DNBI rates associated with ship class, season, and presence of female sailors embarked. The top three DNBI categories associated with the most lost workdays because of sick in quarters and hospitalization were other medical/surgical (36%), infectious gastrointestinal (23%), and all types of nonbattle injury combined (17%).

Health Status↗
PubMed2003

Study of Health in Pomerania (SHIP): a health survey in an East German region. Objectives and design of the oral health section.

The goal of the Study of Health in Pomerania (SHIP) was to estimate the prevalence of diseases, identify potential risk factors in a defined region in northeast Germany, and examine the particular living situation of this population after the reunification of East and West Germany. One of the main concerns of the SHIP design is the analysis of the relationships between dental, medical, social, and environmentally and behaviorally determined health factors. SHIP is a cross-sectional study (clinical findings and sociologic interviews). The sample was drawn in two steps: Thirty-two communities in the region were selected, and within these communities, a simple random sample was drawn from residence registries, stratified by gender and age. The final sample included 4,310 males and females, aged 20 to 79 years. This is equivalent to a participation rate of 68.8%. Data collection was completed in May 2001. The data collection and items comprised four parts: oral health examination, medical examination, health-related interview, and a health- and risk-factor-related questionnaire. The oral health examination included the teeth, periodontium, oral mucosa, morphology and function of the craniomandibular system, and prosthodontics. The medical examination included blood pressure measurements; electrocardiography; echocardiography; carotid, thyroid, and liver ultrasound examinations; neurologic screening; and blood and urine sampling. The computer-assisted interview consisted of questions on symptoms of disease, utilization of medical and dental services, self-assessment of general and oral health, health behavior and knowledge, and socioeconomic variables. The self-administered questionnaire comprised housing conditions, social network, work conditions, subjective well-being, and individual consequences of the German reunification.

Adult↗