Research on ageing in Germany

Research on ageing in Germany

Thomas von Zglinicki*,1

Institute of Pathology, Charite´, Berlin, Germany

Received 18 January 2000; received in revised form 8 February 2000; accepted 10 February 2000

Abstract

The present review on ageing research in Germany is biased towards experimental biogeron-tology, because this is the field which will define the future of ageing research as a whole. Inabsolute numbers of publications between 1995 and 1999, Germany is comparable to other largeEuropean countries. However, Germany ranks definitively last among 10 major developed countriesif the numbers of scientific papers per year are seen in relation to the economic capability. This istrue for the whole of biomedical research, but it is even more exaggerated for ageing research. Thereare potent groups in German ageing research capable of producing a good fraction of high-impactpapers, however. There are many more researchers in areas highly relevant to gerontology whichrecently became attracted by gerontological problems. However, the importance of modern bioger-ontology has not made clear to decision-makers in Germany, so that structural and financiallimitations will probably prevent any significant rise in the near future, which would be necessaryto keep Germany along with other developed countries. © 2000 Elsevier Science Inc. All rightsreserved.

1. Introduction

Any review on ageing research faces the problem of an extremely ill-defined topic.Ageing research is multidisciplinary to an extent which is unheard of in most otherbranches of science. It starts deep in the political sciences with ageing of the populationbeing a major socio-economical challenge of our times. Sociology and psychology of theageing process and of the elderly are extremely important areas of research and interven-tion, and ageing research has even branches in the technical sciences as, for instance, inergonomics. In medicine, geriatrics is essentially a cross-section through most, if not alldisciplines. Similarly ageing, and therefore ageing research, is universal all over biology.

* Tel.: 144-191-256 3325; fax:144-191-219-5074.E-mail address:[email protected]. (T. von Zglinicki)1 Present address: Institute for the Health of the Elderly, Wolfson Research Centre, Newcastle General

Hospital, Newcastle upon Tyne NE4 6BE, UK

Experimental Gerontology 35 (2000) 259–270

0531-5565/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved.PII: S0531-5565(00)00087-5

To some extent, multidisciplinary actually counteracts interdisciplinary. It is not pos-sible to give a balanced overview over so broad a field even within a single country. Onereason is simple lack of knowledge. Moreover, “balanced” means very different views fora socio-gerontologist, a geriatrician, or a biologist, for instance. Even within each disci-pline, defining the boundaries of the ageing research field is a major problem. Inbiomedicine, for example, shall research into age-related diseases be considered asresearch on ageing or not? Surely, the case has been made that research into Alzheimer’sdementia is a major branch of today’s research on ageing. On the other hand, cancer ismuch more often than not an age-associated disease, and basic research on cancer istightly interwoven with research on ageing processes. However, molecular oncology is notnormally considered as a sub-field of ageing research. Another relevant example is cellcycle research. Replicative senescence, the irreversible loss of the ability of somatic cellsto traverse the cell cycle, is an important cellular model of ageing. Much of cell cycleresearch, therefore, will be relevant for research on cell ageing. However, only a smallfraction of cell cycle science will be considered as being part of the ageing research field.Evidently, there is a broad transitional zone between “pure” ageing research and “pure”cell cycle research. As we shall see, these transitional zones in many disciplines can oftenbe regarded as “hidden”ageing research and might be the most important reservoir for thedevelopment of German ageing research in the next future. In this review, the scientificoutput of ageing research in Germany will first be compared to that from other developedcountries using simple publication statistics. The total numbers of publications as coveredby Medline will be the reference, meaning that different areas of ageing research will berepresented fairly as long as their results are published in scientific journals. Next, somemajor results of ageing research in Germany will be reviewed and some structural aspectswill be considered. This will be conducted from the point of view of a biogerontologistand will by necessity reflect the personal view of the author. There are some goodarguments for this bias, including the scope of the journal and the expertise of the author.Also, there are older (Lehr & Brandenburg, 1993) as well as recent (Wahl & Kruse 1999)reviews on psychogerontological and sociogerontological (Wahl & Tesch-Roemer 1998)research in Germany. The important argument is that biogerontology and especiallymolecular biology and genetics has started in recent years to have a major impact ongerontology as a whole. Gerontology was among those areas that were very slow inincorporating modern molecular biology. However, a start has been made in recent years.It was this change that has made biogerontology an attractive and fast developing branchof science in the international arena and that has aroused huge expectations to gerontologyin the public. Models and techniques are now available to tackle experimentally questionswith major impact on human life span and life style in advanced age. We are beginningto understand what ageing is in molecular terms and how its rate can be influenced. Amolecular genetics of ageing is in the making, and we can expect that we will be able soonto identify and avoid or compensate for external and genetic risk factors. The time is ripeto ask to what extent German science contributed to this recent progress.

2. Scientific output in an international comparison

In some areas of ageing research, books are still a much more prestigious way tocommunicate scientific results than articles in journals. In the same areas, internetpublications are presently becoming an accepted means of communications as well.

260 T. von Zglinicki / Experimental Gerontology 35 (2000) 259–270

However, counting numbers of publications in scientific journals should still be acceptableas the first-order approach to measure scientific productivity over all branches of ageingresearch. It can be supposed that the vast majority of all relevant publications in geron-tology is covered by Medline. On that basis, a search for (aging OR ageing OR longevityOR senescence OR lifespan) AND country (in address) will surely include a number ofpapers with no direct relevance to gerontology, and will miss certain important ones, butshould give a rough indication of the output in ageing research in a particular country. Fig.1 displays these data for 10 major developed countries. To give a recent picture, paperswere counted that appeared between January 1, 1995 and December 15, 1999 (There wereno significant trends during this 5-year period). Being closely related both economicallyand scientifically, the Scandinavian countries (Denmark, Finland, Norway, Sweden) weregrouped together. To evaluate the role of research into dementia in the context of ageingresearch, publications on ageing (as defined above) were counted separately depending ontheir use of the key word dementia. Fig. 1 demonstrates that papers on dementia accountfor about one third of all counted papers. Differences in the relative numbers betweencountries are small with the exception of the UK, which boasts a rather large output fromdementia research. Researchers from Germany, too, published a somewhat higher-than-average fraction of papers on dementia research. It is interesting to note that numbers ofpapers referring to both ageing-related key words and to dementia together are small in allexamined countries.

If papers exclusively devoted to dementia research are not taken into consideration(black1 grey bars in Fig. 1), Germany rates number eight out of ten developed countriesin terms of gerontological research output. However, Germany is in a close group with allother large European countries and Canada, preceded only by the US and Japan. Thedifference to the US is enormous: there are more papers on ageing originating from the USthan from the whole rest of the world. On the other hand, differences between the most

Fig. 1. Numbers of papers published between January 1, 1995 and December 15, 1999 in Medline-coveredjournals (PubMed, National Library of Medicine) on ageing (black: aging OR ageing OR longevity ORsenescence OR lifespan NOT dementia), on ageing plus dementia (grey: aging OR ageing OR longevity ORsenescence OR lifespan), and on dementia alone (white: dementia NOT [aging OR ageing OR longevity ORsenescence OR lifespan]) by authors originating from ten major developed countries.

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extreme countries within the European group, UK and Germany, is only about 40papers/year, which amounts to 15 to 17% of the total performance. Inclusion of papers ondementia would put forward Germany to position four in the ranking. However, only theUK stands out significantly from the other European countries if both ageing and dementiaresearch are considered. In Canada and all other large European countries includingGermany, the total scientific productivity in ageing research including dementia remainsvery similar.

This reassuring picture (for German research) changes dramatically, if the scientificoutput is seen in relation to the economic power of the respective countries (Fig. 2). Here,output is measured as number of papers per year (average over the 5-year period1995–1999) per gross national product (GNP, in Mrd EUR). Papers on dementia withoutoutspoken reference to ageing are omitted from this comparison. Output from ageingresearch is compared to the numbers of papers published in all areas of biological andmedical sciences, measured as total numbers of papers by authors from that particularcountry covered by Medline.

Papers on ageing research account for between 1.26% (UK) and 2.21% (Scandinavia;Germany: 1.28%) of all biomedical literature cited in Medline. Comparing these numberswith the percentages for cancer research (USA: 14.9%, UK:13.0%, Germany:17.2%), itappears fair to state a general low share of ageing research. Fig. 2 shows that Germanyranks last among the ten countries compared in respect to the output of both generalbiomedical research and ageing research if related to GNP. Although US americans “earn”about 0.4 ageing research papers and about 20 biomedical papers per year and billion EURGNP, Germans seem to be content with a yearly output of about eight biomedical andslightly more than 0.1 gerontological papers for the same amount of GNP spent. This isan obvious problem of funding: In the US, between 2.35% (1996) and 2.46% (1998) ofGNP were spent to fund research in noncommercial institutions. In Germany, the corre-

Fig. 2. Average numbers of papers published per year between 1995 and 1999 in Medline-covered journals onageing (black: aging OR ageing OR longevity OR senescence OR lifespan) or total biomedical papers (grey) byauthors originating from ten major developed countries, in relationship to the gross national product (GNP, inMrd. EUR) of the respective countries. GNPs are from 1996 to 1998.


sponding fraction of GNP used to fund noncommercial research and development is 0.7%(Statistisches Bundesamt). In both countries, the amount of R and D funds allocated toindustry is about twice the funding of noncommercial institutions. In other words, researchhas a low priority with German political decision makers, and this low priority is exactlyreflected in the output of biomedical scientific literature.

Fig. 2 demonstrates not only a low output of biomedical papers in general but also anadditional deficiency specific to ageing research in Germany. The ageing research outputfrom Japan, which ranks last before Germany, is still about one third higher than theGerman one. The UK is the only country among the ones compared in Fig. 2 with thefraction of the biomedical research devoted to ageing being similarly low as in Germany.However, this fraction refers to about twice the number of biomedical papers per GNP,and it is accompanied by a huge number of papers on dementia (see Fig. 1).

These numerical data raise the question of quality. If German ageing research, at leastif seen in relationship to Germanys economic power, is so bad in numbers, how is itsquality? There is no possibility to assess quality in comparison of all the different areasof ageing research which are covered by the data in Figs. 1 and 2. Publication and citationpatterns vary widely even between quite closely related fields, limiting strongly the use ofimpact factors for cross-sectional comparisons. Uses and misuses of the impact factorhave been discussed widely and controversially (Opthof, 1997, Hecht et al., 1998,Garfield, 1999). Still, within the biological sciences the comparison of publications,stratified with respect to the impact factors of the publishing journals, is one and maybethe only practical possibility to obtain a first-order assessment of the (expected) impact ofa group of papers.

A stratification of papers in gerontological research according to journal impact factorswill essentially measure two factors: First, it will indicate to a large extent the fraction ofbiological, and especially molecular research within gerontology, because those papers dohave a much better chance to be published in high-impact journals. Second, it will indicatehow far authors and reviewers alike believe whether the paper might have an impact onthe biomedical research community as a whole. To strengthen the latter aspect, journalimpact factors of three and ten were chosen as borderlines for stratification. That means,the vast abundance of papers with a more specific relevance to gerontology, whetherbiological, medical or psychological, will be found in the first group. It should bementioned that this group still includes even the leading gerontological journals, a factwhich reflects most of all the (still) small size of the field. That means that papers withhigh relevance to the field are to be found in this group, and is one example to show thatstratification by impact is not synonymous with quality.

The group of papers published in journals with impact factors between three and 10will consist mainly of papers with are thought to be relevant not only to ageing researchbut at least to one or the other branch of biomedical sciences as well. Finally, papers onageing research which make it into highest impact journals are evidently regarded as beingof outstanding quality and importance. Fig. 3 compares the performance of the threecountries, Germany, UK, and USA, in this respect. Journal impact factors were checkedfor papers published in gerontology (defined as above with the exclusion of papers ondementia but not ageing) in 1998 (from the US: only the first 400 papers published in1998). Interestingly, the fraction of high- and highest-impact papers from the US is clearlylower as compared to either the UK or Germany. A nonquantitative survey indicates thatthis difference is due to a much higher fraction of papers devoted to psycho-social aspectsof gerontology in the US. Otherwise, Fig. 3 demonstrates that the percentage of geron-


tological papers published in high- and highest- impact journals from authors in Germanyis at least comparable to that in other countries. To conclude, it has to be stated that theoutput of gerontological research from Germany is low in absolute numbers and isactually embarrassingly low in comparison to Germanys economic power. However,among the papers produced there is a reasonable fraction of publications which areexpected to be of high impact.

3. Biogerontology in Germany: examples

The statistical view pursed so far produced a coarse picture of Germanys presentproductivity in the field of ageing research. Now, a number of examples shall bementioned briefly to illustrate what (in the eyes of the author) might be interesting recentachievements of research in Germany with relevance to biogerontology. This review ismeant to be exemplary, not comprehensive. For reasons given above, it will be heavilybiased towards the biological sciences.

Experimental gerontology starts with theoretical biology, and theories—or better,hypothesis—have always played an exceptional important role in gerontology. In thisrespect, the foundation of the Max Planck Institute for Demographic Research in 1996 inRostock (www.demogr.mpg.de) can be regarded as a stroke of luck for German ageingresearch. Thanks to the interests of its founding director, Prof. J.A. Vaupel, the institutehas a strong commitment to ageing research which is both evident by its recentlypublished papers (Yashin et al., 1999, Vaupel et al., 1998) and by its web-based publi-cations (Demographic Research atwww.demographic-research.organd working papers atwww.demogr.mpg.de/papers). A second, much smaller group interested in theoreticalaspects of ageing is based at the “Innovationskolleg Theoretische Biologie” at theHumboldt University Berlin (Kowald, 1999). Ageing of plants is a branch of gerontologythat tends to be forgotten even by gerontologists themselves. In Germany, a researchgroup “Ageing processes in plants” has recently been established at the University

Fig. 3. Stratification of papers published in 1998 Medline-covered journals on ageing by authors from Germany,the UK or the US according to journal impact factors (IF). Percentages of papers published in journals withimpact factors below 3 (white), between 3 and 10 (grey), or above 10 (black) are indicated.


Bayreuth by funds from the German Research Society (DFG). In fact, this is one of onlytwo among all DFG-funded centre or group grants (“Sonderforschungsbereich”, “Gradu-iertenkolleg”, or “Forschergruppe”) working in the whole field of ageing research pres-ently (The other one is the “Graduiertenkolleg” Psycho-Medical Gerontology at the FreeUniversity Berlin (www.fu-berlin.de/age/), see below). It remains to be seen whether thisgroup will publish high-impact research relevant to plant ageing. There are other groupsinterested in plant senescence based in Frankfurt (Berberich et al., 1999) and in Potsdam(Keller et al., 1999) who published interesting data recently.

Examinations of ageing processes in lower eukaryotes and model animals have had anenormous impact on ageing research in recent years. The use of organisms from yeast toworms to flies which, due to their short generation time, are amenable to both life-spanstudies and powerful molecular genetics has led to the identification of a surprisingly lownumber of genes with major effects on life-span. There is one German group which hascontributed significantly to this most important field by cloning and characterising a geneinvolved in copper homeostasis, oxygen free radical metabolism, and life-span regulationin the fungus Podospora anserina (Osiewacz & Nuber, 1996; Borghouts & Osiewacz,1998).

A closely related hot topic in ageing research is the examination of the function of thesegenes in higher animals. Both gene overexpression approaches (Orr & Sohal, 1994) andmice knockouts (Melov et al., 1998) are in use internationally. In Germany, transgenic andknockout animals are established in dementia research (White et al., 1998; Steiner et al.,1999), but their use in gerontological research has still to start in earnest. For example, thegroup of C. Peters in Freiburg examines cathepsins, has cloned a number of these anddeveloped mouse knockouts (Saftig et al., 1997; Nakagawa et al., 1998). However, thereare no references to ageing studies from this group, although lysosomal cathepsins areknown for long to play an important role in ageing of postmitotic cells (Ivy et al., 1984).

This problem of “hidden” ageing research is even more common in human cell biologyin Germany. Very many potent German groups do research in areas highly relevant forbasic gerontology. Cell cycle regulation, oxidative stress, or DNA damage and repair arejust few obvious examples. Probably due to an uneven distribution of funding possibili-ties, most groups are attracted to areas like oncology, infectiology, immunology, andothers rather than to ageing research. However, as experimental gerontology is becominga fascinating hot topic internationally, more and more German cell biologists feel readyto join the field. Among those who did start in recent years or who plan to start projectsin the cell biology of ageing are, to name just a few, P. Boukamp/Heidelberg on telomeresin cell senescence and immortalisation (Fusenig & Boukamp, 1998), T Grune/Berlin onprotein turnover and the role of PARP in cell ageing (Ullrich et al., 1999), B. Kaina/Mainzon DNA repair (Ochs et al., 1999) or A. Rosenthal/Metagen Berlin who is interested to usechip technology to characterise complex gene expression shifts during senescence.

There is a number of potent groups with long established records in the field of humancell gerontology in Germany. Again, only some examples will be given. The groups of H.Sies and K. Scharffetter-Kochanek (Duesseldorf/Cologne) co-operate in research on themechanisms of photoageing (Berneburg et al., 1999; Hermann et al., 1998). A. Buerkle(Heidelberg/Newcastle) is specialised on the role of PARP in ageing (Muiras et al., 1998).My group demonstrated the causal role of oxidative damage for telomere shortening andsenescence (Saretzki et al., 1999) and, together with T. Grune and others, examined thefunction of lipofuscin in postmitotic cells (Sitte et al., 1999). Lymphocyte ageing both invivo and in vitro is examined in the group of G. Pawelec/Tubingen (Pawelec et al., 1998).


Examining the function of the genes for human segmental progeroid syndromes likeWerner syndrome, or for Ataxia Telangiectasia or Fanconi anemia will contribute greatlyto our understanding of the human ageing process. There are some groups in Germanyworking on the cell and molecular biology of these syndromes as, for instance, H.Hohn/Wuerzburg (de Winter et al., 1999), E. Fritz/Neuherberg (Fritz et al., 1997), or M.Schweiger/Berlin (Ruppitsch et al., 1997).

There are, of course, important contributions to ageing research also from work on lessfancy animal models than transgenics. Hormonal regulation during ageing has beenstudied in the rat for a long time and still remains worth large efforts (Hassan et al., 1999).Many marine animals do not show signs of ageing, and this has been correlated to thepresence of active telomerase in their organs (Klapper et al., 1998).

Despite the often astonishing conservation of genes from yeast to man, human studiesremain the ultimate test to define and/or prove the conditions important for healthy ageingand long life. These comprise vastly different factors from economics via sociology viahealth and diseases to molecular genetics. Studies can be done in completely differentdesigns, for instance as longitudinal or cross-sectional, as population-based, familial ortwin or as centenarian study. There are many studies going on and/or are being evaluatedpresently in different, often European, countries. It is unavoidable that most of them,although rightly be called interdisciplinary, will concentrate on certain aspects and missout others. The first longitudinal ageing study in Germany (Bonn Longitudinal Study onAging - BOLSA), which was performed between 1965 and 1983, concentrated onmedical, social, and psychological aspects of ageing with a strong bias on the latter(Thomae, 1983; Lehr & Thomae, 1987). This approach has set the stage for the morerecent German studies on human ageing: the Berlin Aging Study (BASE, Baltes & Mayer,1999, www.bbaw.de/iag/ag_altern/pub.html), the Interdisciplinary Long-Term Study ofAdulthood and Aging (ILSE, www.dzfa.uni-heidelberg.de/ILSE.hmtl) and the longitudi-nal study Maintaining and Supporting Independent LIving in Old Age (SIMA, www.geronto.uni-erlangen.de). Some biological analysis was included or is planned in thecourse of these studies. For instance, data on ApoE4 genotype in the very old wereobtained from the BASE study (Gessner et al., 1997), and some more molecular biologyis still to be done using the limited amounts of DNA obtained in the course of this study.However, all these studies would have benefited a lot by incorporating from the beginninga strong link to molecular genetics and molecular gerontology.

As the last topic, some German research on age-related disease shall be reviewed. Justas one example to show that there is more to this field than research on dementia, tworecent papers from Tubingen research groups shall be cited which offer new insights in themechanisms of hearing loss, a major problem of the aged (Rusch et al., 1998; Lowenheimet al., 1999). Research into the biological basis of dementia is practically exclusivelyresearch on Alzheimer’s disease in Germany. The field is dominated by the group of K.Beyreuther at the Center for Molecular Biology Heidelberg. The group has characterizedb-Amyloid (Masters et al., 1985) and cloned the Ab precursor protein (APP, Kang et al.,1987). Characterisation of APP and its biological function is still a major focus of thegroup (Weidemann et al., 1997; White et al., 1998; Rossjohn et al., 1999). Proteolyticprocessing of APP and the presenilins is an important issue both in the Beyreuther group(Lichtenthaler et al., 1999) and in the group of C. Haass (formerly Mannheim, nowMunich; Steiner et al., 1999; Haass & Stropper, 1999). To complete the picture, there isalso high-level research in Germany on tau protein, which forms neurofibrillary tangles,the other morphological hallmark of Alzheimer’s disease, by the group of E. Mandelkow/


Hamburg (Friedhoff et al., 1998; Haass & Mandelkow, 1999). Munich is an establishedcentre in Germany for research into non-Alzheimer forms of dementia (Dichgans et al.,1998; Kosel et al., 1999).

4. Structural aspects

Gerontological research in Germany has been shaped as socio- and psychogeronto-logical research by the establishment of a number of professorships in this area (Kassel:Social Gerontology, established 1983; Heidelberg: Gerontology 1986; Erlangen–Nuren-berg: Psychogerontology 1987, www.geronto.uni-erlangen.de; Dortmund: Social Geron-tology 1997; Osnabrueck/Vechta: Social Gerontology 1997). Other German centres in thisarea are at the Max-Planck Institute for Human Development Berlin (www.mpib-berlin.mpg.de/LIP/home-d.htm), at the Free University Berlin (Dept. for Gerontopsycha-try, www.medizin.fu-berlin.de/geronto/), the German Centre for Ageing Research Hei-delberg (www.dzfa.uni-heidelberg.de), or the Centre for Geriatrics and GerontologyFreiburg (www.ukl.uni-freiburg.de/zentral/zggf). None of these centers has establishedeven a single group working on biology of ageing. In contrast, traditions in biogeronto-logical research that existed especially in East Germany (Leipzig, Berlin) were notsupported and did not lead to the establishment of strong, permanent groups. The onlychair presently devoted at least partly to biological gerontology is at the Internal MedicineErlangen–Nuernberg (D. Platt; see Fischer et al., 1995; Dorner et al., 1996). In otherwords, there are no institutionalised modern biogerontological research facilities in allGermany. It must be stated that this situation is in strong contrast to that in all the ninedeveloped countries which were chosen for comparison above. In each of them, there areprofessorships established in the field of the biology of ageing. Even small countries likeDenmark or Austria regard national centers for biogerontological research a necessity.

Although institutionalized biogerontology does not exist in Germany, extramuralfunding is problematic. To my knowledge the only German grant-giving body which hasbiogerontology among its topics is the Verum Foundation (Munich). Unfortunately, thisis not a large foundation, and competition has become fierce in recent years. The attitudeof major German foundations to biological ageing research seems to be rather reluctant.The Volkswagen Foundation, for instance, could not support any form of a “concertedaction” in biogerontology in 1999. The Helmholtz Society appears to be interested inageing research but was not able for lack of money to fund a research association onmolecular mechanisms of ageing as originally suggested in early 1999. The DFG presentlydoes not support any research group or association in biogerontology except the onementioned on plant ageing. There is one structural problem which has to be sorted out bythe ageing researchers themselves. Presently, there are two societies for biological ageingresearch in Germany, namely the section “Biology of Aging” of the German Society forGerontology and Geriatrics (DGGG, www.dggg.uni-erlangen.de) and the “German Soci-ety for Ageing Research” (DGfA, dgfa-aging.de). The problem is that too few reallypotent biogerontologists are members of either, and that none of them is strong enough tolobby efficiently for biological ageing research. Unfortunately, this situation limits thechances for a major improvement in experimental gerontology in Germany further.

To conclude, there is no doubt that the future of the whole ageing research interna-tionally will be defined by biogerontology, and especially by the speed and efficiency withwhich experimental gerontology and molecular biology will merge. The input to society


of this new field of molecular gerontology will be significant far beyond biomedicine.There are a number of potent groups in Germany, and more “hidden” ageing researchersare ready to move in, provided that funds are made available. The potential for a fast rise,not only in quantity but in quality, is there. As the international competition is gainingmomentum recently, this potential has to be exploited soon or will largely be lost. I amafraid that the second choice seems much more probable at present. My consequence? Seemy recent address.

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