The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Ocean dynamics, not dust, have controlled equatorial Pacific productivity over the past 500,000 years

Biological productivity in the equatorial Pacific is relatively high compared with other low-latitude regimes, especially east of the dateline, where divergence driven by the trade winds brings nutrient rich waters of the Equatorial Undercurrent to the surface. The equatorial Pacific is one of the three principal high-nutrient low chlorophyll ocean regimes where biological utilization of nitrate and phosphate is limited, in part, by the availability of iron. Throughout most of the equatorial Pacific, upwelling of water from the Equatorial Undercurrent supplies far more dissolved iron than is delivered by dust, by as much as two orders of magnitude. Nevertheless, recent studies have inferred that the greater supply of dust during ice ages stimulated greater utilization of nutrients within the region of upwelling on the equator, thereby contributing to the sequestration of carbon in the ocean interior. Here we present proxy records for dust and for biological productivity over the past 500 ky at three sites spanning the breadth of the equatorial Pacific Ocean to test the dust fertilization hypothesis. Dust supply peaked under glacial conditions, consistent with previous studies, whereas proxies of export production exhibit maxima during ice age terminations. Temporal decoupling between dust supply and biological productivity indicates that other factors, likely involving ocean dynamics, played a greater role than dust in regulating equatorial Pacific productivity.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 667 - Mitteilung über die Versendung eines Wechsels im Wert von 1.000 Reichstalern

u.a.: Bankhaus Muhl; Mutter von Johanna Schopenhauer; Erbschafssache Andreas Schopenhauer; Immobilien;

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 668 - Mitteilung über die wiederholte Zusendung des Wechsels im Wert von 1.000 Reichstalern

u.a.: Vorwürfe des Sohns; Erbschaftsangelegenheiten in Danzig;

Journeying Beyond the Balcony to the Block Party and Up to 50,000 Feet: Disparities in Children’s Health and Healthcare

Invited Commentary on “Observations from the Balcony: Directions for Pediatric Health Disparities Research and Policy".

Chronology for the EDML ice core from Dronning Maud Land, Antarctica, over the last 150 000 years

A chronology called EDML1 has been developed for the EPICA ice core from Dronning Maud Land (EDML). EDML1 is closely interlinked with EDC3, the new chronology for the EPICA ice core from Dome-C (EDC) through a stratigraphic match between EDML and EDC that consists of 322 volcanic match points over the last 128 ka. The EDC3 chronology comprises a glaciological model at EDC, which is constrained and later selectively tuned using primary dating information from EDC as well as from EDML, the latter being transferred using the tight stratigraphic link between the two cores. Finally, EDML1 was built by exporting EDC3 to EDML. For ages younger than 41 ka BP the new synchronized time scale EDML1/EDC3 is based on dated volcanic events and on a match to the Greenlandic ice core chronology GICC05 via 10Be and methane. The internal consistency between EDML1 and EDC3 is estimated to be typically ~6 years and always less than 450 years over the last 128 ka (always less than 130 years over the last 60 ka), which reflects an unprecedented synchrony of time scales. EDML1 ends at 150 ka BP (2417 m depth) because the match between EDML and EDC becomes ambiguous further down. This hints at a complex ice flow history for the deepest 350 m of the EDML ice core.

Geological map of HANSSONHORNA, Heimefrontfjella, Antarctica (Scale 1:25,000)

Topographic data of this geological map were obtained through stereoscopic aerial photo interpretation. The photogrammetric photo flights were undertaken in 1986 by the Institut für Angewandte Geodäsie, Frankfurt. Horizontal ground control points required for aerial photo interpretation were determined by means of Doppler satellite observation during the 2nd German Neuschwabenland Expedition 1985/86. Vertical ground control points were taken from unpublished map drafts at 1:100 000 scale by Norsk Polarinstitutt, Oslo. The elevation above mean sea level was transferred to Heimefrontfjella barometrically. For this reason assertions concerning the absolute elevation (referred to sea level) are uncertain. Contours and spot heights presented on the map were obtained from the photogrammetric evaluation of the photography taken in 1986; relative elevation data (hight differences) are accurate to approximately ±10 m.

Geological map of RYGHNUTEN, Heimefrontfjella, Antarctica (Scale 1:25,000)

Topographic data of this geological map were obtained through stereoscopic aerial photo interpretation. The photogrammetric photo flights were undertaken in 1986 by the Institut für Angewandte Geodäsie, Frankfurt. Horizontal ground control points required for aerial photo interpretation were determined by means of Doppler satellite observation during the 2nd German Neuschwabenland Expedition 1985/86. Vertical ground control points were taken from unpublished map drafts at 1:100 000 scale by Norsk Polarinstitutt, Oslo. The elevation above mean sea level was transferred to Heimefrontfjella barometrically. For this reason assertions concerning the absolute elevation (referred to sea level) are uncertain. Contours and spot heights presented on the map were obtained from the photogrammetric evaluation of the photography taken in 1986; relative elevation data (hight differences) are accurate to approximately ±10 m.

Geological map of WORSFOLDFJELLET, Heimefrontfjella, Antarctica (Scale 1:25,000)

Topographic data of this geological map were obtained through stereoscopic aerial photo interpretation. The photogrammetric photo flights were undertaken in 1986 by the Institut für Angewandte Geodäsie, Frankfurt. Horizontal ground control points required for aerial photo interpretation were determined by means of Doppler satellite observation during the 2nd German Neuschwabenland Expedition 1985/86. Vertical ground control points were taken from unpublished map drafts at 1:100 000 scale by Norsk Polarinstitutt, Oslo. The elevation above mean sea level was transferred to Heimefrontfjella barometrically. For this reason assertions concerning the absolute elevation (referred to sea level) are uncertain. Contours and spot heights presented on the map were obtained from the photogrammetric evaluation of the photography taken in 1986; relative elevation data (height differences) are accurate to approximately ±10 m.