Wohnst Du noch oder sparst Du schon? Eine vergleichende Untersuchung zur Rolle des Wohneigentums für die Altersvorsorge

Europe’s social security systems face enormous challenges. Most of the existing pension systems do not seem to be sustainable. That means that private pension provision is becoming increasingly important. This paper presents some key findings of an international research project concerning the question of how residential property can be used to ensure liquidity in old age by means of so called equity release schemes (ERS). The analysis covered Germany, Hungary, Ireland, Italy, the Netherlands and the UK. The first part explains the design of the research project. The next two sections present comparison of the national backgrounds regarding pension provision, housing markets and markets for ERS. The study clearly illustrates that residential property will obviously become more important with regard to future old-age provision. Nevertheless, even if the member states face similar problems, a one-size-fits-all-solution does not seem to be feasible. The regulatory, social and economic characteristics of the member states seem to be too diverse

From Solution Shop to Boutique Consulting? Capturing Recent Developments on the German Consulting Market

Digitalization, globalization, new technologies and shorter product life cycles are only a few keywords underlining the fact that companies are under increasing pressure for faster adaptation, innovation and hence applying a higher knowledge intensity. We assume that these conditions require an increasingly important role of consulting companies, because they seem to be the intermediaries needed to bridge the faster growing gaps between existing business models, organizational structures and accelerating market change. Market pressure is growing on the market for consultant companies as well. New technologies and digitalization should influence both the structure of the consultancy market and the business models of consultancies. Christensen suggested a trend from Dzsolution shop” to Dzboutique consulting.” To track current developments, we concentrate on the German consulting market as one of the most important consultant markets worldwide and explore changes of the last two years based on various studies. Processes of change seem to be both substantially driven by digitalization and to reflect change on the non-consultancy markets. A high willingness to switch among providers documents a high pressure on performance. The impact of digitalisation seem to be observable in structural and qualitative change. With regard to the German consulting market and the latest available data we cannot validate a tendency from a dominance of “solution shop” consultancies to “boutique” consultancy service

Hydrochlorothiazide in CLDN16 mutation

Background. Hydrochlorothiazide (HCT) is applied in the therapy of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by claudin-16 (CLDN16) mutation. However, the short-term efficacy of HCT to reduce hypercalciuria in FHHNC has not yet been demonstrated in a clinical trial. Methods. Four male and four female patients with FHHNC and CLDN16 mutation, under long-standing HCT therapy (0.4-1.2 mg/kg, median 0.9 mg/kg, dose according to calciuria), aged 0.7-22.4 years, were included in a clinical study to investigate the effect of HCT on calciuria. The study design consisted of three periods: continued therapy for 4 weeks, HCT withdrawal for 6 weeks and restart of therapy at the same dose for 4 weeks. Calciuria and magnesiuria were assessed weekly as Ca/creat and Mg/creat ratio, every 2 weeks in 24 h urine, and serum Mg, K and kaliuria (s-Mg, s-K and K/creat) at weeks 0, 6, 10 and 14. The data of each study period were averaged and analysed by Friedman and Wilcoxon test. Results. Ca/creat was significantly reduced by HCT (median before/at/after withdrawal 0.76/1.24/0.77 mol/mol creat; n = 8, P<0.05). The reduction of Ca/24 h by HCT was not statistically significant (0.13/0.19/0.13 mmol/kg × 24 h; n = 5). Serum Mg (0.51/0.64/0.56 mmol/l; n = 8, P<0.05) and Serum K (3.65/4.35/3.65 mmol/l; n = 8, P<0.05) were significantly higher during withdrawal. However, Mg/creat (0.98/0.90/0.90 mol/mol creat; n = 8), Mg/24 h (0.14/0.12/0.18 mmol/kg × 24h; n = 5) and K/creat (6.3/8.4/6.2 mol/mol creat; n = 8) remained statistically unchanged during withdrawal. Conclusions. We demonstrated that HCT is effective in reducing hypercalciuria due to CLDN16 mutation on a short-term basis. However, the efficacy of HCT to attenuate disease progression remains to be elucidate

An exceptional Albanian family with seven children presenting with dysmorphic features and mental retardation: maternal phenylketonuria

BACKGROUND: Phenylketonuria is an inborn error of amino acid metabolism which can cause severe damage to the patient or, in the case of maternal phenylketonuria, to the foetus. The maternal phenylketonuria syndrome is caused by high blood phenylalanine concentrations during pregnancy and presents with serious foetal anomalies, especially congenital heart disease, microcephaly and mental retardation. CASE PRESENTATION: We report on an affected Albanian woman and her seven children. The mother is affected by phenylketonuria and is a compound heterozygote for two pathogenetic mutations, L48S and P281L. The diagnosis was only made in the context of her children, all of whom have at least one severe organic malformation. The first child, 17 years old, has a double-chambered right ventricle, vertebral malformations and epilepsy. She is also mentally retarded, microcephalic, exhibits facial dysmorphies and small stature. The second child, a girl 15 years of age, has severe mental retardation with microcephaly, small stature and various dysmorphic features. The next sibling, a boy, died of tetralogy of Fallot at the age of three months. He also had multiple vertebral and rib malformations. The subsequent girl, now eleven years old, has mental retardation, microcephaly and epilepsy along with facial dysmorphy, partial deafness and short stature. The eight-year-old child is slightly mentally retarded and microcephalic. A five-year-old boy was a premature, dystrophic baby and exhibits mental retardation, dysmorphic facial features, brachydactyly and clinodactyly of the fifth finger on both hands. Following a miscarriage, our index case, the youngest child at two years of age, is microcephalic and mentally retarded and shows minor facial anomalies. All children exhibit features of phenylalanine embryopathy caused by maternal phenylketonuria because the mother had not been diagnosed earlier and, therefore, never received any diet. CONCLUSION: This is the largest family suffering from maternal phenylketonuria reported in the literature. Maternal phenylketonuria remains a challenge, especially in woman from countries without a neonatal screening program. Therefore, it is mandatory to be alert for the possibility of maternal phenylketonuria syndrome in case of a child with the clinical features described here to prevent foetal damage in subsequent siblings

Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome.

The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer. AEC mutant proteins exhibit impaired DNA binding and transcriptional activity, leading to dominant negative effects due to coaggregation with wild-type p63 and p73. Importantly, p63 aggregation occurs also in a conditional knock-in mouse model for the disorder, in which the misfolded p63 mutant protein leads to severe epidermal defects. Variants of p63 that abolish aggregation of the mutant proteins are able to rescue p63's transcriptional function in reporter assays as well as in a human fibroblast-to-keratinocyte conversion assay. Our studies reveal that AEC syndrome is a protein aggregation disorder and opens avenues for therapeutic intervention.This work was supported by Telethon Grants GGP09230 and GGP16235 (to C.M.), ERA-Net Research Program on Rare Diseases (ERARE-2) Skin-Dev (C.M.), Italian Association for Cancer Research Grant IG2011-N.11369 (to C.M.), Fondation Dind-Cottier pour la recherche sur la peau (C.M.), DFG Grant DO 545/8-1 (to V.D.), the Centre for Biomolecular Magnetic Resonance, and the Cluster of Excellence Frankfurt (Macromolecular Complexes). P.G. is supported by a Lichtenberg Professorship of the Volkswagen Foundation. C.R. is a PhD student in molecular oncology at the European School of Molecular Medicine

Intrauterine Growth Restriction following Ligation of the Uterine Arteries Leads to More Severe Glomerulosclerosis after Mesangioproliferative Glomerulonephritis in the Offspring

Background: Low birth weight is a risk factor for the development of a more severe course of secondary renal diseases. We tested the hypothesis that experimental mesangioproliferative glomerulonephritis (GN) shows an aggravated course in rats inflicted with experimental uteroplacental insufficiency during gestation. Methods: Intrauterine growth restriction (IUGR) was induced by ligation of both uterine arteries on day 19 in pregnant Wistar rat dams. GN was induced in male offspring at the age of 9 weeks by intravenous injection of an anti-Thy-1.1 antibody. At day 14 of GN, kidneys were taken and analyzed for glomerular morphometry, markers of inflammation, glomerulosclerosis and tubulointerstitial fibrosis. Results: Despite a similar extent of mesangiolysis, former IUGR animals presented with a higher level of glomerulosclerosis and increased deposition of glomerular collagens I and IV compared to nephritic control animals. Arterial blood pressure, renal function, and proteinuria after 14 days of GN were not influenced by former IUGR. Conclusion: Ligation of the uterine arteries in the rat leads to more pronounced sclerotic changes in the glomerulus in the offspring suffering from acute GN. This finding supports the hypothesis that former IUGR increases the susceptibility for a more severe course of secondary renal diseases

The effect of dietary lipid quality in early life on serum LysoPC(18:2) levels and their association with adult blood glucose levels in intrauterine growth restricted rats

Being born small-for-gestational-age, especially with subsequent catch-up growth, is associated with impaired metabolic health in later-life. We previously showed that a postnatal diet with an adapted lipid droplet structure can ameliorate some of the adverse metabolic consequences in intrauterine growth-restricted (IUGR) rats. The aim of the present work was to explore possible underlying mechanism(s) and potential biomarkers. To this end, serum metabolomics was performed in postnatal day (PN) 42 and PN96 samples of the above-mentioned rat offspring, born after uterine vasculature ligation. Blood samples were collected at PN42, directly after a postnatal dietary intervention with either complex lipid matrix (CLM) or control (CTRL) diet, and at PN96 after a subsequent western-style diet (WSD). Offspring of Non-operated (NOP) dams fed CTRL in early life were included as control group. In the PN42 metabolomics data, 11 co-abundance modules of metabolites were identified, of which four were significantly correlated to adult blood glucose levels at PN96. Further analyses showed that Lysophosphatidylcholine(18:2) (LysoPC(18:2)) levels were reduced by ligation (p < 0.01) and restored in CLM fed animals (p < 0.05). LysoPC(18:2) levels at PN42 correlated inversely with adult blood glucose levels. These data indicate that early-life LysoPC(18:2) blood levels may predict adult blood glucose levels and are affected by a postnatal diet with an adapted lipid droplet structure in IUGR offspring

Strategien und Technologien einer pluralistischen Fern- und Nahwärmeversorgung in einem liberalisierten Energiemarkt unter besonderer Berücksichtigung der Kraft-Wärme-Kopplung und erneuerbarer Energien : Kurzfassung der Studie

Die Zusammenfassung dient zwei Zielen: Zunächst werden die wesentlichen Ergebnisse der Langfassung der o.g. Studie referiert; auf dieser Basis werden dann mögliche Maßnahmen und Strategien diskutiert, die kurzfristig (2000-2001) ergriffen werden könnten. Als Akteure kommen hierbei nicht nur die Bundesregierung, die wichtige Rahmenbedingungen zum Marktgeschehen wird setzen müssen, in den Fokus, sondern auch die Betreiber von Heizkraftwerken und KWK-Anlagen und deren Verbände, aber auch andere Akteure wie z. B. Contracting-Unternehmen und Forschungseinrichtungen. Da die Übergangsphase der Liberalisierung der europäischen Stromwirtschaft in den Jahren 2000-2005 eine besondere Herausforderung für die KWK-Entwicklung darstellt, wird auch ein kurzfristig wirksames Maßnahmenbündel zur Diskussion gestellt. Dem Leser sei zum Verständnis in Erinnerung gerufen, dass diese vorgelegte Analyse im Rahmen einer Vorstudie durchgeführt wurde und langfristig abgesicherte Aussagen auch Analysen mit einschließen müssten, die bis 2010 und 2020 reichen. Weiterführende Arbeiten sollen in einer geplanten Hauptstudie erfolgen