Heterogeneity evidence and linkage studies on Charcot-Marie-Tooth disease

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder originally localized to chromosome 1 by linkage to the Duffy blood group. Studies have since shown that the disorder may be heterogeneous, as not all families show this linkage. We tested genetic heterogeneity by the HOMOG computer program in 15 CMT1 pedigrees informative for Duffy. We detected no evidence for heterogeneity in this sample, but when we combined results with previously published lod scores, heterogeneity was statistically significant. Twelve of the 15 families studied did not show linkage to Duffy. We found six of these families to be informative for a chromosome 19 marker, apolipoprotein CII(ApoC2). Despite a previous report showing probable linkage of a non-Duffy-linked CMT1 pedigree to two chromosome 19 markers, we did not detect significant linkage of ApoC2 to CMT1 in these families.

Isolation and use of chromosome 1 probes for linkage studies on Charcot-Marie-Tooth disease

Nine probes were isolated from a human chromosome 1 enriched library and mapped to regions of chromosome 1 using somatic cell hybrid lines. One clone, LR67, which mapped 1q12→q23 detected a BglI RFLP. This probe, as well as 4 other known chromosome 1 markers, α-spectrin, Factor XIIIB, DR10 and DR78, were used for linkage studies in 15 Charcot-Marie-Tooth disease (CMT1) families. Close linking of CMT1 to any of the 5 markers was not indicated. Total lod scores excluded linkage of CMT1 to LR67 and to DR10 at 5 cM or less, to DR78 and 10 cM or less, α-spectrin at 15 cM or less and Factor XIIIB at 20 cM or less. Possible linkage, however, was shown between LR67 and CMT1 at a distance of 30 cM. Also linkage at a distance of 5 cM was detected between this probe and α-spectrin.

DNA probes in Charcot-Marie-Tooth neuropathy

Results of Duffy (Fy) linkage confirm genetic heterogeneity in Charcot-Marie-Tooth disease type 1 (CMT1). Of 11 families informative for Fy, four showed probable linkage with CMT1, seven showed probable non-linkage and two showed definite non-linkage. These results suggest that Fy linked CMT1 may be less common than previously thought. These results combined with those of another DNA probe for the antithrombin III gene confirm that there are at least two gene loci for CMT1, termed 1A and 1B.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Portrait of David Baumgardt with Marie Zweig Portraits Groups

Digital Image

Fin de millénaire eli maailmanlopun satiiri : Frédéric Beigbederin Au secours pardon, Marie Darrieussecqin Truismes ja Michel Houellebecqin La Possibilité d'une île

Pro gradu -työni käsittelee ranskalaisen nykykirjallisuuden yhteiskunnallista suuntausta, jota kirjallisuudentutkija Ruth Cruickshank kutsuu fin de millénaire -kirjallisuudeksi. Tutkimani teokset ovat Frédéric Beigbederin Au secours pardon (2007), Marie Darrieussecqin Truismes (1996) ja Michel Houellebecqin La Possibilité d'une île (2005). Pohdin, millaisena ja millaisin keinoin teokset kuvaavat seksuaalisuutta ja sen tulevaisuudennäkymiä kulutusyhteiskunnassa, ja millaisiin yhteiskunnallisiin olosuhteisiin niiden havainnot perustuvat. Hahmottelen reittejä, joita pitkin globaalin mittakaavan yhteiskunnalliset muutokset vaikuttavat ihmisten intiimeihin tunteisiin ja ihmissuhteisiin. Seksuaalisuuden tarkastelun avulla osoitan, että ranskalaisessa nykykirjallisuudessa ilmenee varsin yhteneviä näkemyksiä ja uhkakuvia aikamme sosiaalisesta todellisuudesta. Tällä tavoin tarkennan ja vankennan vielä hajanaista fin de millénaire -käsitettä. Fin de millénaire -kirjallisuuden oma lajityyppi on massakulttuurin, esimerkiksi viihteen ja mainosten, kielestä vaikutteita ammentava dystopian ja satiirin liitto. Kuten Cruickshank kirjoittaa, fin de millénaire -kirjallisuus heijastaa Ranskassa vuosituhannen vaihteessa korostunutta tunnetta käännekohtaan saapumisesta. Dystopian ohella voidaankin puhua myös apokalyptisesta tekstistä, etenkin siksi, että teokset tarjoavat niukasti ratkaisuja kuvaamiinsa ongelmiin. Eritoten Houellebecqin ja Beigbederin teokset käsittelevät tarpeiden luomista kuluttajille seksuaalivietin ja seksuaalisen kilpailun avulla. Kutsun tätä järjestelmää halutaloudeksi, ja käytän sen toiminnan analysoimisessa apuna Michel Foucault'n käsityksiä vallasta ja Jean Baudrillardin käsityksiä kulutusyhteiskunnasta. Halutalouden sosiaalisia seurauksia ovat vieraantuminen, seksuaalisten hierarkioiden jyrkentyminen ja valinnanvapauden kaventuminen. Teosten kuvaamassa yhteiskunnassa erilaiset esimerkiksi sukupuolen, iän ja ulkonäön perusteella rakentuvat seksuaaliset hierarkiat käyvät yhä merkittävämmiksi. Au secours pardon ja La Possibilité d'une île kuvaavat tapahtumaketjua, jossa etenkin heteromiehistä yhä useampi luisuu seksuaaliseen kurjuuteen muun muassa naisten emansipaation sekä yleisen nuoruuden ja kauneuden palvonnan myötä. Truismesissa taas kuvitellaan yhteiskunta, johon feminismi ei ole päässyt vaikuttamaan mutta pornoistuminen on; naisten ruumiista on tullut miesten yhteistä omaisuutta ja seksuaalinen väkivalta on arkipäivää. Sen maailmassa viehättävä ulkonäkö on naisille miltei elinehto. Yleistäen Houellebecqin ja Beigbederin teokset edustavat miesnäkökulmaa ja Darrieussecqin teos naisnäkökulmaa. Teosten näkemyksiä naisten ja miesten välisistä valtasuhteista pohdin naisten seksuaalisesta vallasta kirjoittaneen Henry Laasasen käyttökelpoisten käsitteiden avulla. Kolmea teosta yhdistävät kuvaukset kulttuurista, jossa ihmissuhteet ovat kaupankäyntiä ja seksuaalinen viehätysvoima määrittelee ihmisen arvon. Darrieussecqin teos on lähitulevaisuuteen sijoittuva dystopia, jossa Beigbederin ja Houellebecqin kuvaama arvoliberalismia ja taloudellista liberalismia yhdistävä kulttuuri on vaihtunut uuskonservatiiviseen ja kaksinaismoralistiseen, naisia räikeästi sortavaan yhteiskuntaan. Teoksen kertoja vähättelee itseensä kohdistuvia koskemattomuuden loukkauksia ja pahoittelee kertomuksensa käänteiden säädyttömyyttä varsinkin kuvatessaan omaa haluaan ja seksuaalista subjektiuttaan. Katson teoksen kritisoivan kirjallisuudentutkija Shirley Ann Jordanin termein poliittisen korrektiuden tyranniaa ja peräänkuuluttavan suoraa puhetta pornografiasta ja naisen halusta. Seksuaalisuus toimii tutkimuksessani lähtökohtana, jonka avulla teoksista nousee esiin julma ja rakkaudeton, säälimättömän kilpailun ja väkivallan täyttämä yhteiskunta. Viime kädessä teosten kuvaama maailmanloppu on se, että rakkaus katoaa ihmisten välisistä suhteista, koska rakkaudessa ei ole voiton tavoittelun kannalta mitään järkeä. Satiirin keinojen, kuten päättymättömän ja monikerroksisen ironian, yhdistyminen dystopiaan pelastaa teokset osoittelevalta moralisoinnilta ja tekee niistä toimivaa yhteiskunnallista kirjallisuutta.

Les fleuves dans l'œuvre romanesque de Jean-Marie Gustave Le Clézio

Relying on Merleau-Ponty's phenomenology of perception and on Mircea Eliade's works on the Sacred and the Profane, this study explores the river as a perceptual space and as the sacred Center in a cosmic vision of the world in twelve of Jean-Marie Gustave Le Clézio's fictional works, from The Interrogation (1963) to Revolutions (2003). In the first chapter, after introducing the field of study, I discuss the relation between the radical subjectivity and the evasiveness of perceiving subjects in Le Clézio's fiction. Next are some thoughts on the relation between Merleau-Ponty's and Le Clézio's ideas. The second chapter studies the river as an experience in the text, first as a topographical space, then as a sound world. The investigations move on to its water as a visual and a tactile phenomenon. Then follows the human use of the river, the (absence of) baths, and the river as a traveling space. The chapter closes with the study of the metaphorical use of the word, occurring mainly in urban space and for phenomena in the sky. The third chapter is organized around the river as the Center of the world in a religious cosmogony, where the river represents the origin of the world and of the human race. The core analysis shows how the middle of the river is a symbolic space of a new beginning. As a sacred space, the river abolishes time as the object of contemplation and as relative immobility from the point of view of a person drifting downstream. The functions of a new beginning and of abolition of time are combined in the symbolic immersions in the water. Finally, the dissertation explores other symbolical spaces, such as the unknown destination of the drift, and the river as the Center of a utopia. The chapter closes with the existential agony as a result of the elimination of the Center in the urban environment. In the final chapter, the river is compared to other watercourses : the creek, the brook and the rapids. The river is more of a spatial entity, whereas the actual water is more important in the smaller watercourses. The river is more common than the other watercourses as a topographical element in the landscape, whereas the minor watercourses invite the characters to a closer contact with their element, in immersions and in drinking their water. Finally, the work situates the rivers in a broader context of different fictional spaces in Le Clézio's text.

Marie Curie Symposium 8.-9.12.2011 Helsingissä : tiivistelmät

Suomalaista radiokemiaa esittelevä Marie Curie Symposium järjestetään Helsingissä 8.-9.12.2011 osana Kansainvälistä Kemian Vuotta 2011. Samalla juhlistetaan Marie Curien sata vuotta sitten, 10.12.1911, saamaa kemian Nobel-palkintoa. Marie Curie, maailman ensimmäinen radiokemisti, sai Nobel-palkintonsa luonnossa olevien radioaktiivisten alkuaineiden poloniumin ja radiumin keksimisestä. Tämä raportti sisältää symposiumissa esitettyjen tieteellisten tiedonantojen tiivistelmät

Is the Species Flock Concept Operational? The Antarctic Shelf Case

There has been a significant body of literature on species flock definition but not so much about practical means to appraise them. We here apply the five criteria of Eastman and McCune for detecting species flocks in four taxonomic components of the benthic fauna of the Antarctic shelf: teleost fishes, crinoids (feather stars), echinoids (sea urchins) and crustacean arthropods. Practical limitations led us to prioritize the three historical criteria (endemicity, monophyly, species richness) over the two ecological ones (ecological diversity and habitat dominance). We propose a new protocol which includes an iterative fine-tuning of the monophyly and endemicity criteria in order to discover unsuspected flocks. As a result nine « full » species flocks (fulfilling the five criteria) are briefly described. Eight other flocks fit the three historical criteria but need to be further investigated from the ecological point of view (here called « core flocks »). The approach also shows that some candidate taxonomic components are no species flocks at all. The present study contradicts the paradigm that marine species flocks are rare. The hypothesis according to which the Antarctic shelf acts as a species flocks generator is supported, and the approach indicates paths for further ecological studies and may serve as a starting point to investigate the processes leading to flock-like patterning of biodiversity. © 2013 Lecointre et al.