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

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

Strategien und Technologien einer pluralistischen Fern- und Nahwärmeversorgung in einem liberalisierten Energiemarkt unter besonderer Berücksichtigung der Kraft-Wärme-Kopplung und regenerativer Energien : Kurztitel: Pluralistische Wärmeversorgung ; AGFW-Hauptstudie - erster Bearbeitungsabschnitt. Band 1, Grundlagen der Kraft-Wärme-Kopplung, Zertifizierungsverfahren und Fördermodelle

Die im vorliegenden Band 1 vorgestellten Ergebnisse sollen der Begleitung der anstehenden KWK-Gesetzgebung in technischer und wirtschaftlicher Hinsicht dienen. Das derzeitige KWK-(Vorschalt-)Gesetz, welches durch ein neues mit klareren Kriterien verbundenes Gesetz ersetzt werden soll, ist in mehrfacher Hinsicht problematisch, da es Regelungen zum Auffangen von Stranded Investments mit Regelungen zur Förderung von KWK vermischt, keine klare Definition von KWK enthält, industrielle KWK ausgegrenzt und durch die intransparente Förderstruktur das Mittelaufkommen und die Mittelverwendung nicht nachvollziehbar macht. Ein KWK-Ausbau wird sich in der gegenwärtigen Situation des Strommarktes nur auf der Basis einer Förderung entwickeln können (vgl. Vorstudie). Obwohl neue KWK-Anlagen im Vergleich zu neuen Anlagen der ungekoppelten Erzeugung unter Vollkostenbedingungen meist günstiger abschneiden, benötigen sie vor dem Hintergrund des aktuell auf dem Niveau kurzfristiger Grenzkosten geführten Preiskampfes zusätzliche Deckungsbeiträge. Die Analyse der Vielzahl vorgeschlagener Zertifizierungskriterien hat ergeben, dass definierter KWK-Strom eine geeignete Messgröße darstellt. Ausführliche Analysen zeigen, dass die Bestimmung dieses Stromanteils mit Hilfe einer einmaligen Anlagenzertifizierung relativ unproblematisch ist. Eine weitere Differenzierung des so definierten KWK-Stroms, z. B. hinsichtlich der CO2-Effizienz, birgt dagegen die Gefahr so krasser Fördergegensätze zwischen alten und neuen Anlagen sowie zwischen gas- und kohlegefeuerten Anlagen, dass dadurch vorhandene, für zukünftige Anwendungen prädestinierte Standorte verloren gehen könnten und die sinnvolle Auskopplung großer Wärmemengen aus Steinkohlekraftwerken unterbleibt. Die Bewertung verschiedener Fördermodelle ergibt kein eindeutiges Bild, welches Fördermodell zu bevorzugen wäre. Andererseits zeigt sich, dass sich aus allen Bausteinen von Förderinstrumenten ein sinnvolles Instrumentenmix konstruieren lässt

Inhibition of TGF-β Signaling and Decreased Apoptosis in IUGR-Associated Lung Disease in Rats

Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-β system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-β signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-β system was determined at P1 and P70. TGF-β signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-β1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-β signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-β-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-β signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-β signaling may contribute to the pathological processes of IUGR-associated lung disease