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Sediment records left by coastal hazards (e.g. tsunami and/or storms) may shed light on the sedimentary and hydrodynamic processes happening during such events. Modern onshore and offshore sediment samples were compared with the 2004 Indian Ocean Tsunami, three palaeotsunami and a 2007 storm deposit from Phra Thong Island, Thailand, to determine provenance relationships between these coastal overwash deposits. Sedimentological and stratigraphic characteristics are generally inadequate to discriminate tsunami and storm deposits so a statistical approach (including cluster analysis, principal component analysis and discriminant function analysis) was used based on grain size, mineralogy and trace element geochemistry. The mineral content and trace element geochemistry are statistically inadequate to distinguish the provenance of the modern storm and tsunami deposits at this site, but the mean grain size can potentially discriminate these overwash deposits. The 2007 storm surge deposits were most likely sourced from the onshore sediment environment whereas all four tsunami units statistically differ from each other indicating diverse sediment sources. Our statistical analyses suggest that the 2004 tsunami deposit was mainly derived from nearshore marine sediments. The uppermost palaeotsunami deposit was possibly derived from both onshore and nearshore materials while the lower palaeotsunami deposits showed no clear evidence of their sediment sources. Such complexity raises questions about the origin of the sediments in the tsunami and storm deposits and strongly suggests that local context and palaeogeography are important aspects that cannot be ignored in tsunami provenance studies. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version

Coastal overwash deposits from tsunamis and storms have been identified and characterised from many coastal environments. To date, these investigations have utilised ad-hoc time, energy and cost intensive invasive techniques, such as, pits and trenches or taking core samples. Here, we present the application of high-frequency ground penetrating radar (GPR) to identify and characterise the 2004 Indian Ocean Tsunami (IOT) and palaeotsunami deposits from Phra Thong Island, Thailand. This site is one of the most intensively studied palaeotsunami sites globally and preserves a series of late-Holocene stacked sandy tsunami deposits within an organic, muddy low-energy backbeach environment. Using 100, 500 and 1000 MHz GPR antennas, 29 reflection profiles were collected from two swales (X and Y) inland of the modern beach, and two common mid-point (CMP) profiles using the 200 MHz antennas were collected from Swale Y. Detailed examination of the CMPs allowed accurate velocity estimates to be applied to each profile. The reflection profiles included across-swale profiles and a high-resolution grid in Swale X, and were collected to investigate the feasibility of GPR to image the palaeotsunami deposits, and two profiles from Swale Y where the tsunami deposits are poorly known. The 500 MHz antennas provided the best stratigraphic resolution which was independently validated from the stratigraphy and sedimentology recovered from 17 auger cores collected along the profiles. It is clear from the augers and GPR data, that the different dielectric properties of the individual layers allow the identification of the IOT and earlier tsunami deposits on Phra Thong Island. Although applied in a coastal setting here, this technique can be applied to other environments where thin sand beds are preserved, in order to prioritise sites for detailed examination.

The spatial variability of Holocene relative sea-level (RSL) change influences the capacities of coastal environments to accommodate a sedimentary record of paleoenvironmental change. In this study we couch a specific investigation in more general terms in order to demonstrate the applicability of the relative sea-level history approach to paleoseismic investigations. Using subsidence stratigraphy, we trace the different modes of coastal sedimentation over the course of time in the eastern Indian Ocean where RSL change evolved from rapidly rising to static from 8000 yr ago to present. Initially, the coastal sites from the Aceh, Sumatra, coastal plain, which are subject to repeated great earthquakes and tsunamis, built up a sedimentary sequence in response to a RSL rise of 1.4 mm/yr. The sequence found at 2 sites 8 km apart contained 3 soils of a mangrove origin (Rhizophora, Bruguiera/Ceriops, Avicennia pollen, and/or intertidal foraminifera) buried by sudden submergence related to coseismic subsidence and 6 tsunami sands that contain pristine subtidal and planktic foraminifera. After 3800 cal yr B.P. (years before A.D. 1950), sea level stabilized and remained such to the present. The stable relative sea level reduced accommodation space in the late Holocene, suggesting that the contaggradation of the coastal plain was a consequence of periodic coastal inundation by tsunamis

We present stratigraphic, archeological and historical evidence for two closely timed predecessors of the giant 2004 tsunami on the northern coast of Aceh, northern Sumatra. This is the first direct evidence that a tsunami played a role in a fifteenth century cultural hiatus along the northern Sumatran portion of the maritime silk route. One seacliff exposure on the eastern side of the Lambaro headlands reveals two beds of tsunamigenic coral rubble within a small alluvial fan. Radiocarbon and Uranium-Thorium disequilibrium dates indicate emplacement of the coral rubble after 1344 ± 3 C.E. Another seacliff exposure, on the western side of the peninsula, contains evidence of nearly continuous settlement from ~1240 C.E. to soon after 1366 ± 3 C.E., terminated by tsunami destruction. At both sites, the tsunamis are likely coincident with sudden uplift of coral reefs above the Sunda megathrust 1394 ± 2 C.E., evidence for which has been published previously. The tsunami (or tsunami pair) appears to have destroyed a vibrant port community and led to the temporary recentering of marine trade dominance to more protected locations farther east. The reestablishment of vibrant communities along the devastated coast by about 1500 CE set the stage for the 2004 disaster.

The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here we present an extraordinary 7,400 year stratigraphic sequence of prehistoric tsunami deposits from a coastal cave in Aceh, Indonesia. This record demonstrates that at least 11 prehistoric tsunamis struck the Aceh coast between 7,400 and 2,900 years ago. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda megathrust ruptures as large as that of the 2004 Indian Ocean tsunami., Tsunamis can be an extremely hazardous event, but understanding their occurrence through past records remains challenging. Here, the authors document tsunami occurrence from a 7,400 year old record of tsunami deposits in a cave in Indonesia, helping us to reconstruct the frequency of earthquakes in the region.

Many recreation impact studies have focused on summer activities, but the environmental impact of winter recreation is poorly characterized. This study characterizes the impact of snowshoe/cross-country ski compaction and snowmelt erosion on trails. Trail cross-sectional profiles were measured before and after the winter season to map changes in erosion due to winter recreation. Compacted snow on the trail was 30 % more dense than snowpack off the trail before spring melt out. Snow stayed on the trail 7 days longer. Soil and organic material was transported after spring snowmelt with −9.5 ± 2.4 cm2 total erosion occurring on the trail transects and −3.8 ± 2.4 cm2 total erosion occurring on the control transect (P = 0.046). More material was transported on the trail than on the control, 12.9± 2.4 versus 6.0 ± 2.4 cm2 (P = 0.055), however, deposition levels remained similar on the trail and on the control. Snow compaction from snowshoers and cross-country skiers intensified erosion. Trail gradient was found to be significantly correlated to net changes in material on the trail (R 2 = 0.89, ρ = −0.98, P = 0.005). This study provides a baseline, showing that non-motorized winter recreation does impact soil erosion rates but more studies are needed. Trail managers should consider mitigation such as water bars, culverts and avoiding building trails with steep gradients, in order to reduce loss of soils on trails and subsequent sedimentation of streams.

The Holocene stratigraphy of the coastal plain of the Aceh Province of Sumatra contains 6 m of sediment with three regionally consistent buried soils above pre-Quaternary bedrock or pre-Holocene unconsolidated sediment. Litho-, bio-, and chronostratigraphic analyses of the lower buried soil reveals a rapid change in relative sea-level caused by coseismic subsidence during an early Holocene megathrust earthquake. Evidence for paleoseismic subsidence is preserved as a buried mangrove soil, dominated by a pollen assemblage of Rhizophora and/or Bruguiera/Ceriops taxa. The soil is abruptly overlain by a thin tsunami sand. The sand contains mixed pollen and abraded foraminiferal assemblages of both offshore and onshore environments. The tsunami sand grades upward into mud that contains both well-preserved foraminifera of intertidal origin and individuals of the gastropod Cerithidea cingulata . Radiocarbon ages from the pre- and post-seismic sedimentary sequences constrain the paleoearthquake to 6500–7000 cal. yrs. BP. We use micro-and macrofossil data to determine the local paleoenvironment before and after the earthquake. We estimate coseismic subsidence to be 0.45 ± 0.30 m, which is comparable to the 0.6 m of subsidence observed during the 2004 Aceh–Andaman earthquake on Aceh’s west coast.

Background Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm of endothelial origin with clinical behavior intermediate between hemangioma and angiosarcoma. The natural history of EHE is highly variable. This study uses an Internet registry to identify clinical patterns with prognostic significance in EHE. Methods Cases from the International Hemangioendothioma, Epithelioid Hemangioendothelioma, and Related Vascular Disorders (HEARD) Support Group were evaluated based on demographics, organ involvement, disease progression, presence or absence of pleural effusion, and treatment. Survival among various cohorts was compared using log-rank analysis of Kaplan-Meier plots. Results Two hundred sixty-four patients were identified from April 2004 to November 2009. Fifty-eight cases were excluded because of inadequate information or wrong diagnosis. EHE was more common in female patients (61%). Male gender and age ≥ 55 years were associated with decreased survival. The most commonly affected organs were liver, lung, and bone. No specific organ or combination of organ involvement differentially affected survival, and survival was no different between patients with multiple vs single organ involvement. However, pattern B, defined as lesions without distinct borders (eg, pulmonary infiltrates, pleural effusion, ascites), hemoptysis, or involvement of more than two bones adversely affected survival in all cohorts. Conclusion A novel staging system with prognostic value for EHE is proposed. Pleural effusion or other signs of uncontained tumor growth, hemoptysis, and osseous involvement of more than two bones implied worse survival than did localized and discrete tumors, regardless of number of organs involved. A lay registry can provide useful insights into the clinical behavior of a rare cancer.

The Longitudinal Valley fault in eastern Taiwan is the most important arc–continent collisional boundary fault between the Philippine Sea plate and the Eurasian continent. The 50% amount of collisional deformation partitioned on the fault has considered implications for seismic hazard. Our paleoseismological work on the middle segment (the Juisui fault) of the Longitudinal Valley fault has shown that the fault occurred intensive seismicity of four paleoearthquakes of 1951 AD, P2 event

Stratigraphic relations recorded in boreholes drilled along the Shanchiao fault, a normal fault that bounds the western margin of metropolitan Taipei, reveal evidence of early–mid Holocene subsidence and active extension of the Taipei Basin. Paleoseismic data suggest that the maximum displacement for each subsidence event ranges from 2.3 to 4.5 m. Despite large uncertainties, the large offsets imply earthquake magnitudes that range in size from 6.9 to 7.1. Our results suggest that large magnitude earthquakes along the Shanchiao fault are one of the major seismic hazards in the metropolitan Taipei area.

The 1999 Chichi earthquake ruptured along previously unrecognized traces of the Chelungpu fault, because the traces were covered with thick-bedded fluvial, alluvial, and colluvial deposits. The earthquake created a 95-km-long surface rupture and associated fault-related fold scarps. This study focused on the fault-related fold at two locations, where the fold scarp is characterized with trench excavation and shallow cored boring results. The structural characteristics revealed by the two trench sites are consistent with a trishear fault-propagation fold growth above a blind thrust. Several characteristics of the fold observed in the Holocene deposits show smoothly rounded fold-hinges, unconformities, onlapped structure, and downward steepening of forelimb strata. Results from these structures suggest that the fold grows by progressive limb rotation of growth strata in sequential coseismic growth episodes. The growth strata show several unconformable contacts as indicated by paleosoil horizons developed on event horizons. Based on the syntectonic sedimentary structure, three events are revealed at the Siangong-Temple site and two paleoearthquake events on the Shijia site. Integration with the two trenches and the previous studies suggests the three paleoearthquake events occurred 300–430, 710–800, and 1710–1900 yr B.P. These data on the two trench sites indicate that the average slip rate is 4.2 and 4.5 mm/yr, respectively.

Paleoseismic data from the Mesquite Lake fault reveal evidence for up to four prehistoric earthquakes since the latest Pleistocene, with three large surface- rupturing events in about the past 10.2 ka. Three events were recorded in trenches excavated for this investigation on Mesquite Lake playa. A buried fault scarp brack- eted by accelerator mass spectrometer radiocarbon ages of detrital charcoal indicate that a mid to late Holocene event occurred between about 2.7 and 7.4 ka, most likely between about 3.9 and 4.6 ka. An early Holocene rupture defined by a subtle buried scarp and upward-terminating fissures is bracketed between about 7.7 and 10.2 ka. Evidence for an inferred late Pleistocene event prior to about 10.2 ka includes a subtle scarp, upward termination of faults, folding, and in-filled craters and fissures. A previous paleoseismic investigation just south (2 km) of the playa identified at least one event in the past 1.3 ka, although this event was not identified in this study at the playa site. Apparent vertical offsets of about 1.0 m and 1.2 m for the last two events at the playa site suggest a sequence of similar serial ruptures. These separa- tions are comparable to the height of surficial scarps just south of the playa. Because the vertical separations produced by each event are similar, the Mesquite Lake fault, at least locally, experiences similar slip-per-event. Since the initiation of Holocene playa development just over 10.2 ka ago, we estimate a horizontal slip rate of 0.7- 0.9 mm yr 1 that is consistent with slip rates for other faults in the eastern California shear zone. Despite large uncertainties, event stratigraphy at the playa site shows that periods of quiescence up to thousands of years separated large ruptures, similar to other faults in the eastern California shear zone. Comparison of paleoseismic studies in the eastern California shear zone suggest that the Mesquite Lake, and possibly the Bullion and Lavic Lake faults in the eastern part of the shear zone may have failed during periods of seismic quiescence in the western part of the zone, at about 1- 5 ka. This suggests that seismic strain release may vary spatially across the shear zone and that temporal clusters of earthquakes are not necessarily spatially limited to specific regions.

Geologic observations of the Chinese Tian Shan foreland reveal active, contractional deformation along the entire margin. To quantify the amount of shortening and understand the structural style, we mapped the stratigraphy and structure of four folds expressed at the western end of the foreland, north of Kashi. In this region, upper Tertiary through Quaternary sediments are conformable, but an abrupt transition from parallel to unconformable bedding in the uppermost strata suggests a transition from pre-fold strata to strata deposited on a growing fold. The folds have very steep (60–90°) limbs and are box-like to isoclinal, suggestive of detachment folding. Total north–south shortening across the center of the region is >9 km, of which 5–7 km occurred in the Kashi–Atushi fold system. Shortening estimates determined with excess area methods for individual folds decrease from a maximum of 6.8 km in the northwest to a minimum of 0.7 km in the southeast. Timing derived from a paleomagnetic study shows that the transition to syn-folding strata occurred ∼1.2 Ma in the middle of the study area, resulting in an average shortening rate for the Kashi–Atushi fold system of ∼5 mm/yr if folding was coeval. The shortening rate is high compared with foreland deformation east of the study area, suggesting that the regional stresses or response of the foreland stratigraphy are unique to the Kashi–Atushi fold system kinematics.

We mapped and analyzed two vertical exposures—exposed on the walls of a 3- to 5-m-deep, 70-m-long excavation and a smaller 3-m-deep, 10-m-long excavation—across the 1999 rupture of the Chelungpu fault. The primary exposure revealed a broad anticlinal fold with a 2.5-m-high west-facing principal thrust scarp contained in fluvial cobbly gravel beds and overlying fine-grained overbank deposits. Sequential restoration of the principal rupture requires initial failure on the basal, east-dipping thrust plane, followed by wedge thrusting and pop-up of an overlying symmetrical anticline between two opposing secondary thrust faults. Net vertical offset is about 2.2 m across the principal fault zone. From line-length changes, we estimate about 3.3 m of horizontal shortening normal to fault strike. The ratio of these values yields a total slip of 4.0 m and an estimate of about 34 for the dip of the fault plane below the excavation. This value is nearly the same as the 35 average dip of the fault plane from the surface to the hypocenter. Restoration of the exposed gravelly strata and adjacent overbank sediments deposited prior to the 1999 event around the principal rupture suggests the possible existence of a prior event. A buried 30-m-wide anticlinal warp beneath the uplifted crest of the 1999 event is associated with three buried reverse faults that we interpret as evidence for an earlier episode of folding and faulting in the site. The prior event is also recorded in the smaller excavation, which is located 40 m south and is oriented parallel to the larger excavation. Radiocarbon dating of samples within the exposed section did not place tight constraints on the date of the previous event. Available data are interpreted as indicating that the previous event occurred before the deposition of the less than 200 14 C yr B.P. overbank sands and after the deposition of the much older fluvial gravels. We interpret the previous event as the penultimate event relative to the 1999 ChiChi earthquake. We estimated the long-term slip rate of the Chelungpu fault to be 10–15 mm/yr during the last 1 Ma, based on previously published retrodeformable cross sections. This rate is, however, significantly higher than geodetic rates of shortening across the Chelungpu thrust where two pairs of permanent Global Positioning System stations suggest 7–10 mm/yr of shortening across the fault. Given the 4 m of average slip, the long-term slip rate yields an interseismic interval of between 267 and 400 yr for the Chelungpu fault.

A vertical exposure across the principal thrust scarp of the 1999 Mw 7.6 earthquake allows quantification offault slip. The exposure is located on the active Chelungpu fault near Wufeng, along the range front of the fold-and-thrust belt in western Taiwan. The 1999 surface ruptures at the Wufeng site are characterized by a west-facing 2 to 3 m high principal thrust scarp and an east-facing lesser backthrust scarp. We mapped a 15 mlong, 5 m-deep exposure across the principal thrust scarp and characterized complex deformation structures, which include a main basal thrust fault, a wedge thrust, and a pop-up anticlinal fold with two secondary opposing thrust faults. The vertical displacement across the principal thrust scarp is measured directly from the offsets of the same sedimentary horizons between the hangingwall and the footwall. The average vertical displacement is 2.2 ^ 0.1 m, and the maximum displacement is 2.5 m, at the crest of the small pop-up fold. Horizontal displacement estimates were determined using line- and area-balancing methods. With line-length methods we estimated a horizontal displacement of 3.3 ^ 0.3 m across the principal scarp for four sedimentary horizons. For area balancing, first we selected three horizontal soil/sand deposits with a total thickness of about 0.5 m. The estimate yields an average horizontal displacement of 4.8 ^ 1.0 m. Using these individual and relatively thin stratigraphic layers yielded significant standard deviations in displacement estimates as a result of thickness variations. Second, we used the 3 mthick overbank soil/sand and the lower part offluvial pebble/cobble to calculate a horizontal displacement of 2.6 ^ 0.2 m with the area-balancing technique. According to the geometry of the dip angle (35‐ 408) of the basal thrust, the line-length measurement and the 3 m-thick package area balancing both providedreasonable results of horizontal displacement. By comparing thedifferent deposits applied to theline- and area-balancing methods, we interpret that decoupling of deformation occurred between the lower fluvial gravels and the upper overbank sand and mud deposits. Due to lesser confining pressure at the surface, additional deformation occurred in the upper 1 ‐ 2 m thick overbank deposits. This additional deformation yielded further vertical uplift of 0.3‐ 0.5 m and horizontal displacement of 0.2 ‐ 0.8 m around the core of the pop-up fold. Our work suggests that determination of slip across surface thrust ruptures varies as a function of the mechanical behavior of young late Quaternary deposits. q 2003 Elsevier Ltd. All rights reserved.

The southwestern Chinese Tian Shan of Central Asia is an actively deforming part of the Indian–Asian collision system. Paleomagnetic investigations of two Plio–Pleistocene terrestrial successions provide the first detailed magnetostratigraphy for the upper Cenozoic strata in this region. Paleomagnetic samples were collected from 358 sites within the Atushi Formation and Xiyu Formation across the Atushi–Talanghe anticline near Atushi. Thermal demagnetization behavior, reversal and fold tests of paleomagnetic stability indicate that the characteristic remanence directions were acquired before tilting and folding of the strata. A composite magnetostratigraphic section for this sequence correlates with the Mammoth subchron to the Jaramillo subchron, between 3.3 and 1.07 Myr, of the geomagnetic polarity timescale of Cande and Kent [J. Geophys. Res. 100 (1995) 6093–6095]. The mean declination (349±3°) in the Boguzihe section indicates a counterclockwise vertical-axis rotation (−11±2°) during the past 1.4 Myr. The conglomeratic Xiyu Formation is time-transgressive along its progradational contact with the underlying Atushi Formation across a map distance of ∼6 km; the basal contact ranges from less than 1.0 Myr in the Ganhangou section to 1.9 Myr in the Boguzihe section to the southwest, and to ∼2.8 Myr on the northwest limb of the anticline. Northeastward lateral propagation and growth of the Atushi–Talanghe anticline initiated at ∼1.4 Myr in the Boguzihe, and ∼1.2 Myr in the Ganhangou. The cross section in the Boguzihe provides a conservative (maximum) estimate of shortening rate of ∼3.3 (4.4) mm/yr and uplift rate of ∼3 mm/yr. This rate represents about half of the geodetically determined shortening rate between the northern Tarim Basin and the Kyrgyz Tian Shan [Wang et al., Acta Seismol. Sin. 22 (2000) 263–270; Reiger et al., Earth Planet. Sci. Lett. 191 (2001) 157–165]. During fold growth over the past 1.4 Myr, the crest of the Atushi–Talanghe anticline eroded at an average rate of 2.6–2.7 mm/yr.

Opsoclonus-myoclonus syndrome (OMS) is seen in 2-3% of children with neuroblastoma and is believed to be caused by an autoimmune process elicited by the tumor. Although long-term neurologic sequelae are common in children with OMS, limbic encephalitis has not previously been reported. We report a child who developed limbic encephalitis associated with anti-Hu antibodies, 6 years after her initial diagnosis of neuroblastoma and OMS. This case demonstrates that patients with neuroblastoma and OMS are at risk for developing new paraneoplastic symptoms years after their original diagnosis and emphasizes the need for careful long-term follow-up.

Ground-Penetrating Radar (GPR) is a wellestablished technique for investigating the sub-surface stratigraphy in sandy coastal environments. GPR is most commonly applied in sandy coastal settings to determine the environmental evolution of an area. Several studies have used GPR to investigate the impact of storms through the identification of erosional scarps and very few have used GPR to investigate coastal overwash deposits. Here we present GPR profiles collected from a swale near the west coast of Phra Thong Island, Thailand, a key site where the 2004 Indian Ocean Tsunami and three earlier tsunamis deposited 5 to 20 cm thick, sandy deposits that are easily distinguished by intervening organic mud layers. We utilised 100, 500 and 1000 MHz antennas to image the spatial continuity of the sand-mud interface. The 100 MHz antennas demarcate the contact between the swale and underlying beach ridge stratigraphy, whereas the 1000 MHz antennas were poor at resolving the swale’s internal stratigraphy. The 500 MHz antennas resolved the tsunami sand-organic mud contacts clearly as evidenced from auger cores collected along the profiles. The 500 MHz profiles clearly show where the 2004 tsunami partially scoured the back of the beach ridge and deposited sands over the back-beach environment. Our results confirm the utility of GPR to characterise sandy overwash deposits in muddy environments, which has applications for a range of coastal and fluvial settings around the globe.

New geologic mapping, structural studies, geochronology, and diffusion erosion modeling along the Deep Springs fault, California, shed light on its Quaternary faulting history. The Deep Springs fault, a 26km-long, predominantly north-northeaststriking, west-northwestdipping normal fault bounding the eastern side of Deep Springs Valley, cuts Jurassic batholithic rocks nonconformably overlain by middle Miocene to Pleistocene stream gravels, coarse-grained sand, tuffaceous sand, unwelded to partially welded tuff, and Bishop ash, as well as Quaternary coarse- to finegrained alluvial fan deposits. The 40 Ar/ 39 Ar geochronology yields ages of 3.09 0.08 Ma for the unwelded tuff and 753 4k a for the Bishop ash. Holocene debris flows, a landslide, and recent alluvium bury the youngest fault scarp. The Deep Springs fault is characterized by multiple fault planes and fault scarps that become progressively younger toward the basin. The dip of the fault plane varies from 20 to 87 and fault-plane and striation measurements indicate an average orientation of N23E, 47NW, and N77E, 49SW, respectively. The offset of Bishop ash and underlying tuff across the Deep Springs fault indicates horizontal extension and vertical slip rates of 0.7 and 0.9 mm/yr, respectively, since the eruption of the Bishop Tuff, and 0.2 and 0.2 mm/yr, respectively, since the eruption of the unwelded tuff. If the vertical slip rate since the eruption of the Bishop Tuff has remained constant through time, then slip along the Deep Springs fault began ca. 1.7 Ma. Younger fault scarps to the west of the bedrock fault cut Quaternary deposits; scarp offset ranges from 0.8 to 17.5 m and scarp slope angle ranges from 8 to 37. Topographic profiling of the smallest, least eroded fault scarps, with an average surface offset of 2.7 m, indicates that these scarps developed as the result of a single earthquake and ruptured an 20km-long segment of the fault. Radiocarbon analyses on detrital charcoal, located in the footwall block of one of these scarps, yield an age of 1.960 0.055 ka. Diffusion erosion modeling of these fault scarps yields an elapsed time of 1.7 0.5 k.y. since these fault scarps formed. Making reasonable assumptions about the depth of this earthquake and shear modulus, we estimate a moment magnitude, MW 7.0, for this earthquake. The Deep Springs fault is one of several displacement-transfer normal faults that define a zone of distributed deformation between subparallel right-lateral strike-slip faults east of the Sierra Nevada that make up the northern part of the eastern California shear zone. The young age and recent earthquake activity along the Deep Springs fault are consistent with a model proposed for the kinematic evolution of this part of the eastern California shear zone.

High-precision GPS geodesy in the Pacific Northwest provides the first synoptic view of the along-strike variation in Cascadia margin kinematics. These results con- strain interfering deformation fields in a region where typical earthquake recurrence intervals are one or more orders of mag- nitude longer than the decades-long history of seismic moni- toring and where geologic studies are sparse. Interseismic strain accumulation contributes greatly to GPS station veloci- ties along the coast. After correction for a simple elastic dis- location model, important residual motions remain, especially south of the international border. The magnitude of northward forearc motion increases southward from western Washington (3-7 mm/yr)to northern and central Oregon (-9 mm/yr), con- sistent with oblique convergence and geologic constraints on permanent deformation. The margin-parallel strain gradient, concentrated in western Washington across the populated Puget Lowlands, compares in magnitude to shortening across the Los Angeles Basin. Thus crustal faulting also contributes to seismic hazard. Farther south in southern Oregon, north- westward velocities reflect the influence of Pacific-North America motion and impingement of the Sierra Nevada block on the Pacific Northwest. In contrast to previous notions, some deformation related to the Eastern California shear zone crosses northernmost California in the vicinity of the Klamath Mountains and feeds out to the Gorda plate margin.

Purpose: To assess the role of consolidative radiation therapy (CRT) in conjunction with myeloablative therapy with or without total body irradiation (TBI) in children and young adults with metastatic or recurrent sarcoma. Methods and Materials: Twenty-one pediatric sarcoma patients with metastatic (10) or recurrent (11) disease were entered on a prospective feasibility study of intensive myeloablative therapy with or without TBI. Median patient age was 17.8 years (range, 9.4–24.7 years). Primary histologies included Ewing’s (12) , PNET (3) , and other soft tissue sarcomas (6) . Twenty patients received induction chemotherapy. Myeloablative therapy consisted of TBI in 11 patients with either high dose melphalan/etoposide (9) or high dose cytoxan/thiotepa (2) . TBI consisted of 12 Gy in 2 Gy fractions delivered twice daily over 3 days. Ten patients received high dose chemotherapy alone, either with thiotepa/carboplatinum/etoposide (8) or cytoxan/carboplatinum (2) . Myeloablative therapy was followed by autologous stem cell rescue (ASCR) 24 to 48 hours after completing chemotherapy. Fourteen patients (67%) received CRT either prior to (5) or following (9) myeloablative therapy. Median CRT dose was 37.2 Gy (range, 20–60). Fifty-one disease sites were present prior to myeloablative therapy. Twelve (24%) were bulky (> 8 cm) and 18 (35%) underwent surgical debulking. The median follow-up of surviving patients was 15 months (range, 8–20) with 25% of patients having been followed for more than 20 months. Results: The 3-year actuarial disease-free (DFS) and overall survival (OS) rates for the entire group were 36% and 27%, respectively. Following myeloablative treatment, responses were: 11 complete, 6 partial, 1 stable, and 3 progressive disease. Sixteen patients (71%) have relapsed. The most common site of relapse was the lung (13) . Of the 51 disease sites present prior to myeloablative therapy, 36 sites (71%) were amenable to CRT. Non-amenable sites were: multiple lung metastases (13) and bone marrow (2) . Twenty-six amenable sites (51%) received CRT either prior to (14) or following (12) ASCR. Amenable sites treated with CRT had a better 3-year actuarial local control (80 vs 37%) ( p = 0.0065) than amenable sites not treated with CRT. Factors associated with improved disease-free survival (DFS) in univariate analysis were induction chemotherapy response ( p = 0.002) and extent of surgical resection ( p = 0.045). There was a trend toward improved DFS on univariate analysis with the use of TBI as part of myeloablative therapy ( p = 0.07). The one factor associated with improved OS on univariate analysis was induction chemotherapy response ( p = 0.007). Multivariate analysis revealed that induction chemotherapy response is the only factor that remains significant for DFS ( p = 0.032) as well as for OS ( p = 0.017). Patients with complete response to induction therapy had 40% probability of survival versus all other patients who had 10% survival ( p = 0.05). Conclusion: Consolidative radiotherapy is feasible in primary metastatic or recurrent pediatric sarcoma patients treated with myeloablative therapy with or without TBI. CRT to sites amenable to irradiation provided an improved 3-year actuarial local control than that seen in sites amenable to CRT that did not undergo radiotherapy. There was a trend for improved DFS with the use of TBI. Improved DFS and OS can be predicted by response to induction therapy. This intensive regimen may improve the cure rate of advanced pediatric sarcomas in select patients.

We present the results of our mapping of a 5.6-km length of the central Emerson fault that ruptured during the 1992 Landers earthquake in the southwestern Mojave Desert, California. The right-lateral slip along this portion of the rupture varied from about 150 to 530 cm along the main rupture zone. In some locations a total of up to 110 cm of additional right-lateral slip occurred on secondary faults up to 1.7 km away from the main rupture zone. Other secondary faults carried up to several tens of centimeters of left-lateral or thrust displacement. The maximum net vertical displacement was 175 cm, east-side-up. The sense of vertical slip across the main fault zone varied along strike, but in most cases it was consistent with the sense of vertical slip in previous earthquakes, as indicated by the locations of areas of older, uplifted, and abandoned alluvial fan surfaces. Although variations in surficial slip have been reported along previous strike-slip ruptures, our closely spaced slip measurements allow a much more detailed study of slip variability than was possible previously. We document variations in slip as large as 1 m or more over distances ranging from 1–2 km to a few tens of meters, suggesting that strains of the order of 10−1 may have occurred locally within the surficial sediments. The long-wavelength (kilometer-scale) variations in surficial slip may be influenced by fault geometry and perhaps by the thickness of unconsolidated sediments. The slip variations over shorter length scales (tens of meters) may be caused by variations in the proportion of the total shear that occurs on visible, brittle fractures versus that which occurs as distributed shear, warping or rotation. The variability of slip along the ruptures associated with the Landers earthquake calls for caution in interpreting geomorphic offsets along prehistoric fault ruptures.

The Sierra Madre fault, along the southern flank of the San Gabriel Mountains in the Los Angeles region, has failed in magnitude 7.2 to 7.6 events at least twice in the past 15,000 years. Restoration of slip on the fault indicated a minimum of about 4.0 meters of slip from the most recent earthquake and suggests a total cumulative slip of about 10.5 meters for the past two prehistoric earthquakes. Large surface displacements and strong ground motions resulting from greater than magnitude 7 earthquakes within the Los Angeles region are not yet considered in most seismic hazard and risk assessments.

Excavations in a playa along the 1992 rupture of the Emerson fault reveal evidence of two paleoseismic events, with only one large prehistoric rupture in the past 15 millennia. Accelerator mass spectrometer radiocarbon ages of charcoal from playa sediments and from fault-scarp colluvium directly beneath the playa beds indicate that the last large prehistoric slip event occurred about 9000 ka. Trench-wall exposures revealed clear evidence of at least one pre-9 ka rupture at the playa site. The event horizon of this earthquake is between two pedogenic carbonate layers that have radiocarbon ages of 14.8 ka and 24.1 ka, implying that the earthquake occurred about 20,000 years B.P. The actual bracketing ages for this rupture are likely a few thousand years older because of the mean residence time for the pedogenic carbonate and calibration of the 14C ages by 230Th dating. Despite the large uncertainties, a dormant period of at least 6 kyr to as much as 13 kyr separates the older event from the 9 ka event. Because the scarp formed by the penultimate event is similar in height to the scarp formed by the 1992 Mw 7.3 Landers earthquake, the penultimate rupture was, at least locally, similar in size to the most recent rupture. This similarity supports the concept of characteristic slip for the Emerson fault. Preliminary results from paleoseismic studies at other sites on the 1992 rupture suggest that large ruptures occurred on other nearby faults within a few hundred years of this penultimate event on the Emerson fault. The interseismic period that preceded the 1992 earthquake on the Emerson fault was about 40 times longer than the average interval between large events on the nearby San Andreas fault. Therefore, in comparison to events on the San Andreas fault, the 1992 Landers earthquake was an exceedingly rare event Published version

Langerhans cell histiocytosis (LCH) is an unusual indication for orthotopic liver transplantation in children. Data from limited case reports suggest that orthotopic liver transplantation for LCH is associated with excellent survival rates and a low incidence of disease recurrence. However, in our experience, children who have transplantation for LCH appeared to experience a high incidence of refractory rejection and posttransplant lymphoproliferative disease (PTLD).Data from 398 liver transplants performed in 298 children younger than 16 years of age were reviewed to determine the presence of risk factors for PTLD in patients with LCH and other causes of liver failure.The incidence of PTLD was significantly higher in children who received transplants for LCH compared with all indications (p0.001) and specific indications that were associated with the development of PTLD (p0.002). Among patients in whom PTLD developed, there was no significant difference in the incidence of primary Epstein-Barr virus infections in patients who receive transplantation for LCH (4/4, 100%) versus all other indications (12/14, 86%). Children who had transplantation for LCH were older than those who had transplantation for other indications (LCH median age 3.1 years, other indications 1 year). The incidence of rejection, especially refractory rejection, was greater in patients who had transplantation for LCH (100% and 50%, respectively) compared with those who had transplantation for other indications (70% and 10%, p0.02 for refractory rejection).Patients who had transplantation for liver disease related to LCH experienced a 67% long-term survival (median follow up 5.8 years, range 2.1 to 7.5 years). Recurrent LCH occurred in only 33% of patients and was easily managed. However, PTLD developed in two thirds of these patients, perhaps in part because of the high incidence of refractory rejection. This series therefore demonstrates an association between a primary disease process and the development of PTLD. Although the data indicate that children with LCH-induced liver failure benefit from transplantation, special care must be exercised in screening for and preemptive treatment of PTLD.

Living-related donor liver transplantation (LDLT) is an accepted approach to pediatric liver transplantation. Parental donation imposes a significant risk of chimerism with graft-versus-host disease (GVHD) because donors homozygous at all HLA loci (1.6% of the population) present no mismatched HLA antigens to be recognized by their offspring's immune system. The case of a 9-month-old who underwent LDLT with her 23-year-old HLA-homozygous mother as a donor demonstrates the consequences of this occurrence. The patient developed GVHD with aplastic anemia; the patient's nucleated peripheral blood elements were shown to be entirely derived from the donor. Later, after some marrow recovery, the patient's circulating lymphocytes had a donor origin, while the marrow-derived neutrophils had a recipient origin. The patient suffers from chronic GVHD and debilitating skin disease several years posttransplant. Our current protocol calls for HLA typing to eliminate parents who are homozygous at all HLA loci as donors of hepatic allografts to their children.

The incidence, risk factors, and outcome of posttransplant lymphoproliferative disease (PTLD) were examined for 298 children undergoing liver transplantation. The overall incidence of PTLD was 8.4% (25 of 298). Intensity of immunosuppression was found to be a major risk factor for the development of PTLD. Cyclosporine and tacrolimus when used as primary immunosuppression were associated with the development of PTLD in 4.3% and 6.6% of cases (P=NS). OKT3 and tacrolimus, when used as rescue therapy for steroid-resistant rejection, were associated with a comparable increase in the risk of developing PTLD (10.9% and 11.1%, P=NS). Patients requiring both OKT3 and tacrolimus to treat refractory rejection were at significantly increased risk for PTLD (28.1% vs. 4.3% or 6.6%, P

About half of the 8 cm/yr of oblique convergence across the active convergent plate boundaries of Taiwan occurs in eastern Taiwan, across the Longitudinal Valley. Significant shortening and left‐lateral slip occurs across the Longitudinal Valley fault there, both as shallow fault creep and as seismogenic fault slip. The southernmost Longitudinal Valley fault comprises an eastern Peinan strand and a western Luyeh strand. We derive an interseismic block model for these two strands using data from a small‐aperture Global Positioning System (GPS) campaign and leveling. The model provides estimates of fault slip rates and quantifies slip partitioning between the two strands. A 45 mm/yr dip‐slip rate on the northern Peinan strand diminishes southward, whereas the left‐lateral component increases. In contrast, nearly pure dip‐slip motion of about 20 mm/yr on the southern Luyeh strand diminishes northward to about 8 mm/yr and picks up a component of left‐lateral motion of about 15 mm/yr before it dies out altogether at its northern terminus. The Luyeh and the northern Peinan strands record near‐surface creep, but the southern Peinan strand appears locked. The potential earthquake magnitude for the two strands may be as high as M_w 6.5. We anticipate seismic rupture mainly on the locked portion of the Peinan strand.

[1] Stratigraphic evidence is found for two coseismic subsidence events that underlie a floodplain 20 km south of Padang, West Sumatra along the Mentawai segment (0.5°S–0.3°S) of the Sunda subduction zone. Each earthquake is marked by a sharp soil-mud contact that represents a sudden change from mangrove to tidal flat. The earthquakes occurred about 4000 and 3000 cal years B.P. based on radiocarbon ages of detrital plant fragments and seeds. The absence of younger paleoseismic evidence suggests that late Holocene relative sea level fall left the floodplain too high for an earthquake to lower it into the intertidal zone. Our results point to a brief, few thousand year window of preservation of subsidence events in tidal-wetland stratigraphic sequences, a result that is generally applicable to other emergent coastlines of West Sumatra.

Opsoclonus-myoclonus syndrome (OMS) is seen in 2-3% of children with neuroblastoma and is believed to be caused by an autoimmune process elicited by the tumor. Although long-term neurologic sequelae are common in children with OMS, limbic encephalitis has not previously been reported. We report a child who developed limbic encephalitis associated with anti-Hu antibodies, 6 years after her initial diagnosis of neuroblastoma and OMS. This case demonstrates that patients with neuroblastoma and OMS are at risk for developing new paraneoplastic symptoms years after their original diagnosis and emphasizes the need for careful long-term follow-up.

Hyperdiploidy with greater than or equal to 50 chromosomes is a frequent and distinct karyotypic pattern in the malignant cells of children with acute lymphoblastic leukemia. To understand better the mechanism of formation of the hyperdiploid karyotype, we studied 15 patients using 20 DNA probes that detect restriction fragment length polymorphisms. We first examined disomic chromosomes for loss of heterozygosity. Two patients had widespread loss of heterozygosity on all informative disomic chromosomes, and represent cases of near- haploid leukemia in which the chromosomes doubled. One other patient had loss of heterozygosity limited to chromosome 3; in this patient all of seven other informative disomic chromosomes retained heterozygosity. Loss of heterozygosity was not detected in the remaining 12 patients on a total of 87 informative disomic chromosomes. We then examined tetrasomic chromosomes for parental dosage. Of the 13 patients in whom widespread loss of heterozygosity was not present, 11 patients had tetrasomy 21; 10 of 11 (91%) had an equal dose of maternal and paternal alleles on chromosome 21 and only 1 of 11 (9%) had an unequal dose of parental alleles in a 3:1 ratio. These results suggest that the hyperdiploid karyotype usually arises by simultaneous gain of chromosomes from a diploid karyotype during a single abnormal cell division, and occasionally by doubling of chromosomes from a near- haploid karyotype. The hyperdiploidy in cases without widespread loss of heterozygosity is not caused by stepwise or sequential gains from a diploid karyotype or by losses from a tetraploid karyotype; the former should result in a 3:1 parental dosage for 67% of tetrasomic chromosomes (9% observed) and the latter should result in loss of heterozygosity for 33% of disomic chromosomes (1% observed). Additional studies of the molecular basis for this leukemia subtype are warranted.

Successful cytogenetic analysis of malignant tissues using conventional techniques depends upon the presence of viable, dividing malignant cells in the sample, and the ability to obtain metaphase cells with good-quality chromosome banding. Even when these necessary conditions are met, many tumors have complex karyotypes that may be difficult to define completely or have subtle chromosomal abnormalities that are difficult to detect. Overall, determination of the karyotype of a malignant tissue is a time-consuming and labor-intensive process, and for some tumors, is associated with a significant technical failure rate

We have examined a population of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) for loss of heterozygosity of polymorphic markers on chromosomes 5 and 7. The rationale for this study was the observation that the majority of patients with therapy- related leukemia (t-AML or t-MDS), resulting from cytotoxic treatment for prior malignancies, have loss of chromosome 5 and/or 7 or deletions involving the long arms of one or both of these chromosomes. This cytogenetic finding suggested that tumor-suppressor genes, important in the development of AML, may be located in these chromosomal regions. We analyzed a total of 60 patients, 43 with primary MDS/AML de novo and 17 with t-MDS/t-AML. Leukemia cells were evaluated for restriction fragment length polymorphisms (RFLPs). Leukemia cell genotypes were compared with lymphoblastoid cell genotypes from the same patients. Two cases of loss of heterozygosity were identified from chromosomes lacking visible deletions: one involving chromosome 5 in a patient with AML de novo who had a visible deletion of 5q at a later stage of the disease, and one involving chromosome 7 in a patient with t-AML. We conclude that allele loss from loci on chromosomes 5 and 7 in MDS/AML, when it occurs, usually results from major deletion or simple chromosome loss, rather than from mitotic recombination or chromosome loss with duplication of the remaining homologue.

Patients undergoing bone marrow transplantation often receive total body or total lymphoid irradiation as part of the conditioning regimen prior to marrow infusion. The cytogenetic effects of this therapy on skin fibroblasts were studied. Fibroblast cultures from eight skin biopsies were harvested in early passages for G-banded chromosome analysis. Four biopsies were from three patients who had high-dose cyclophosphamide and total body radiotherapy; one was from within and one was from outside the radiation field of a patient who had high-dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had combination chemotherapy alone, and one was from a normal control. No abnormal mitoses were found in the control or the patient who had chemotherapy alone, and only two of 30 mitoses from skin outside the lymphoid radiotherapy field were abnormal. However, most cells (49-88%) from five biopsies within radiotherapy fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and contained multiple balanced rearrangements, of which reciprocal translocations were most common. The data indicate that the radiotherapy used for bone marrow transplantation induces extensive, sustained chromosome abnormalities in vivo in skin fibroblasts.

Long-term slip rates for the Denali Fault in southern Alaska are derived using 10Be cosmogenic radionuclide (CRN) dating of offset glacial moraines at two sites. Correction of 10Be CRN model ages for the effect of snow shielding uses historical, regional snow cover data scaled to the site altitudes. To integrate the time variation of snow cover, we included the relative changes in effective wetness over the last 11 ka, derived from lake-level records and δ 18O variations from Alaskan lakes. The moraine CRN model ages are normally distributed around an average of 12.1 ± 1.0 ka (n = 22, ± 1σ). The slip rate decreases westward from ∼13 mm/a at 144°49′W to about 7 mm/a at 149°26′W. The data are consistent with a kinematic model in which southern Alaska translates northwestward at a rate of ∼14 mm/a relative to a stable northern Alaska with no rotation. This suggests progressive slip partitioning between the Denali Fault and the active fold and thrust belt at the northern front of the Alaska range, with convergence rates increasing westward from ∼4 mm/a to 11 mm/a between ∼149°W and 145°W. As the two moraines sampled for this study were emplaced synchronously, our suggestion of a westward decrease in the slip rate of the Denali Fault relies largely upon the measured offsets at both sites, regardless of any potential systematic uncertainty in the CRN model ages. Published version

The presence of a chromosomal translocation in the leukemic cells at diagnosis of acute lymphoblastic leukemia (ALL) in children is associated with a high risk for treatment failure. We have reexamined the relationship between translocations and prognosis in 146 children with ALL who received risk-based therapy such that high-risk patients were treated with intensive drug schedules. In univariate analysis, multiple factors were associated with a relatively poor event-free survival (EFS) including age less than 2 years or greater than 10 years (combined group), WBC count greater than 10 x 10(9)/L, French-American-British (FAB) morphologic classification L2, absence of common ALL antigen (CALLA, CD10) expression, absence of hyperdiploidy with a chromosome number of 50 to 60, and presence of the specific translocations t(4; 11)(q21;q23) or t(9;22)(q34;q11) (combined group). However, there was no disadvantage with respect to EFS in patients with translocations compared with those who lacked translocations (73% at 4 years in both groups). Furthermore, when patients with specific cytogenetic abnormalities for which the prognostic significance has been well established (hyperdiploid 50 to 60, t(4;11), and t(9;22] were removed from the analysis, the remaining group with other translocations had a better EFS than the remaining group lacking translocations, although this was not statistically significant (81% v 65% at 4 years, P = .24). In a multivariate analysis, a model including WBC count and FAB classification was the strongest predictor of EFS. The presence or absence of translocations was not an independent predictor of EFS and did not contribute to the ability of any model to predict EFS. In conclusion, when effective intensive therapy is used to treat childhood ALL with high-risk clinical features, categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor.

We have studied 20 children with therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were 3 months to 16 years old at diagnosis of their primary neoplasm and 1 to 24 years old at diagnosis of their secondary neoplasm. The median interval from initial treatment for the first malignancy to diagnosis of therapy- related MDS or AML was 46 months (range, 12 to 116 months). Twelve patients had chromosomal abnormalities resulting in loss of material from the long arm of chromosomes 5 and/or 7, three patients had abnormalities of chromosome 11 band q23, one patient had both classes of abnormalities, three patients had other abnormalities, and one patient had a normal karyotype. Ten of 12 patients with chromosome 5 and/or 7 abnormalities had been exposed to an alkylating agent, and two of three patients with 11q23 abnormalities had been exposed to an epipodophyllotoxin. The patient with both classes of abnormalities had been exposed to both types of therapy. We conclude that abnormalities of chromosomes 5 and/or 7 are common in children with therapy-related MDS or AML. The proposed relationships between exposure to alkylating agents and abnormalities of chromosomes 5 and/or 7 and between exposure to epipodophyllotoxins and abnormalities of 11q23 are supported in this pediatric series.

Fragments of Upper Jurassic to Lower Cretaceous volcanic and basinal strata constitute the Gravina belt in southeast Alaska. In the Ketchikan area the Gravina belt is made up of two lithotectonic units. The lower unit consists of coarse marine pyroclastic and volcaniclastic strata, mafic flows, breccia, and fine-grained tuff which are locally intruded by hypabyssal bodies of diorite and quartz diorite. The volcanic rocks are characterized by tholeiitic arc basalts, lack felsic volcanic strata, and overlie Upper Triassic and older strata of the Alexander terrane. Augite and/or hornblende-bearing porphyritic rocks are common and locally intrude the Alexander terrane basement, where they are thought to represent the intrusive equivalents of lavas within the section. Age constraints for the volcanic unit, based on structural and stratigraphic relations with adjacent units, are late Middle to Late Jurassic. The Gravina belt upper unit consists of fine- to coarse-grained turbidites and related conglomeratic channel-fill deposits. The basinal rocks unconformably overlie Permian and Triassic rocks of the Taku terrane and remnants of the lower volcanic part of the Gravina sequence which overlie the Alexander terrane. The conglomerate units contain mostly volcanic and plutonic lithic clasts, some of which yield Pb-U zircon ages of 154–158 Ma. The predominance of pyroclastic deposits interbedded with massive flows, tuff, breccia, and argillaceous turbidites, and the lithologic and chemical composition of the volcanic rocks indicate a submarine volcanic arc setting for the Gravina sequence. The basinal pyroclastic rocks are inferred to have been shed from submarine stratovolcanos during the Late Jurassic. Epiclastic rocks were deposited as submarine fans, derived in part from erosion of a magmatic arc. The presence of fine-grained tuffaceous turbidites implies ongoing, but distant, volcanism. The pyroclastic and volcaniclastic rocks represent remnants of a Late Jurassic oceanic arc constructed on a composite basement consisting of the Alexander and Taku terranes. The strata accumulated in an intra-arc basin on the eastern edge of the Alexander terrane. The volcanic and basinal rocks were deformed during a major mid-Cretaceous intra-arc contractional event, in conjunction with the emplacement of a distinctly younger, arc-related plutonic suite.

Fragments of upper Paleozoic and lower Mesozoic metavolcanic and metasedimentary sequences of the Taku terrane are exposed discontinuously along a narrow belt in southeast Alaska and form a distinct lithostratigraphic package in the Ketchikan area called the Alava sequence. Crinoidal and argillaceous marble, carbonaceous phyllite, argillite, mafic flows, pillow breccia, pyroclastic tuff, and quartzite characterize the sequence. These strata are unconformably overlain by Upper Jurassic to Lower Cretaceous fine- to coarse-grained epiclastic rocks of the Gravina sequence. The upper Paleozoic part of the Alava sequence may be correlative with the Yukon–Tanana terrane, whereas the Middle and Upper Triassic portion of the Alava sequence may represent a metamorphic vestige of the Stikine terrane. Both parts are now exposed on the western flank of the Coast Plutonic Complex, in contrast with their correlatives to the east. These relations suggest that the Stikine and Alexander terranes were juxtaposed prior to deposition of the Gravina sequence. The western boundary between rocks of North American affinity and allochthonous ensimatic crustal fragments of the Alexander and Wrangellian terranes lies west of the Coast Plutonic Complex.

Bone marrow cells from two pediatric patients completing therapy for acute lymphoblastic leukemia were studied using in situ hybridization with an alpha-satellite DNA probe specific for chromosome 17. Morphologic analysis of the end-therapy specimens from each patient had shown small numbers (7.5%, 8.5%) of cells that were suspicious for residual or recurrent disease. These cells could not be morphologically or immunophenotypically distinguished with certainty from immature lymphoid cells (hematogones), which may be present normally, sometimes in increased numbers, in the bone marrow specimens of children. In situ hybridization with a probe to chromosome 17 was used because the leukemic cells from each patient had originally been shown to have an extra copy of this chromosome. In one patient, in situ studies showed a population of cells (106 of 1,000 cells) with three hybridization signals indicating trisomy 17, and thus residual/recurrent leukemia. In the other patient trisomy 17 could not be detected. Additional hybridizations to previously stained bone marrow aspirate smears permitted a direct correlation of the cytogenetic findings with the suspicious cells on a cell-to-cell basis. The questionable cells were identified, photographed, and then re-examined after hybridization. In one patient, 13 of 18 (72%) of the suspicious cells were found to have trisomy 17, whereas in the other patient 0 of 24 (0%) demonstrated an extra copy of this chromosome. These cases illustrate a clinical application of interphase cytogenetic analysis and demonstrate how this technology can be used for direct correlation of cytogenetic findings with cell morphology. This technique should prove useful for the detection of minimal residual disease and for lineage studies in leukemia and myelodysplasia.

The recurring chromosomal 9;II translocation [t(9; II) (p22;q23)] typically is associated with acute monoblastic leukemia, but a number of patients with acute lymphoblastic leukemia also have been reported to have the t(9; II). To investigate the cell lineage in the latter cases, we analyzed DNA from the leukemic cells of an 8-year-old girl with acute lymphoblastic leukemia and a t(9;I I) for rearrangements of the immunoglobulin and T-cell receptor genes. Rearrangements of both immunoglobulin heavy-chain loci and of one lambda light-chain gene were detected, as well as deletions affecting both alleles of the kappa light-chain genes; T-cell receptor genes were in germline configuration. These results provide further evidence that the 9; I I translocation is not limited to myeloid lineage leukemia and may be observed in acute lymphoblastic leukemia.

We have identified an identical reciprocal translocation between the long arms of chromosomes 3 and 21 with breakpoints at bands 3q26 and 21q22, [t(3;21)(q26;q22)], in the malignant cells from five adult patients with therapy-related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Primary diagnoses were Hodgkin's disease in two patients and ovarian carcinoma, breast cancer, and polycythemia vera in one patient each. Patients had been treated with chemotherapy including an alkylating agent for their primary disease 1 to 18 years before the development of t-MDS or t-AML. We have not observed the t(3;21) in over 1,500 patients with a myelodysplastic syndrome or acute myeloid leukemia arising de novo or in over 1,000 patients with lymphoid malignancies. We have previously reported that the t(3;21) occurs in Philadelphia chromosome-positive chronic myelogenous leukemia (CML). Thus, the t(3;21) appears to be limited to t-MDS/t-AML and CML, both of which represent malignant disorders of an early hematopoietic precursor cell. These results provide a new focus for the study of therapy-related leukemia at the molecular level.

Ten patients with strongly Ki-1(CD30)-positive non-Hodgkin's lymphoma (NHL) were identified at our institution during the past 5 years. Based on morphology, the lymphomas of five of these patients were classified as anaplastic large-cell lymphoma (ALCL); the lymphomas of four patients lacked the morphologic features of ALCL (non-ALCL); and the lymphoma of one patient was unclassifiable. Significant clinical and cytogenetic differences were observed between patients with ALCL and those with non-ALCL. The patients with ALCL tended to be young at the time of diagnosis. They presented with peripheral lymphadenopathy, and two of the five patients had skin involvement. An identical reciprocal translocation involving chromosomes 2 and 5 [t(2;5)(p23;q35)] was observed in lymph nodes from each of the two ALCL patients whose chromosomes were studied. Four of the five patients with ALCL are alive and in complete remission 10-27 months after receiving systemic chemotherapy. In contrast, the patients with non-ALCL were heterogeneous with respect to clinical findings. All of the non-ALCLs were histologically aggressive; however, their morphology varied. The t(2;5) was absent in the lymphoma specimens from each of three non-ALCL patients studied. Three of the four patients died within 17 months after receiving systemic chemotherapy. Thus, differences in morphology are correlated with differences in the clinical findings, karyotype, and outcome in Ki-1-positive NHL.

Structural rearrangements involving the short arm of chromosome 9, including bands 9p21 and 22, are found in the leukemia cells of 7 to 13 percent of patients with acute lymphoblastic leukemia. The interferon-alpha gene cluster and the interferon-beta 1 gene have been localized to this chromosomal region. We have previously demonstrated deletions of these genes in several cell lines established in vitro from patients with lymphoblastic leukemia. We report here homozygous or hemizygous deletions of the interferon-alpha and interferon-beta 1 genes in samples of leukemia cells from patients with lymphoblastic leukemia. Of 62 patients examined, 18 (29 percent) had such deletions. Four patients (7 percent) had homozygous deletions of the interferon-alpha gene cluster; of these, one also had a homozygous deletion and three had hemizygous deletions of the interferon-beta 1 gene. Fourteen patients (23 percent) had hemizygous deletions of both the interferon-alpha gene cluster and the interferon-beta 1 gene. In 8 of the 18 patients with deletions, the deletions of interferon genes were submicroscopic; in the 11 other patients, chromosomal rearrangements of 9p, including translocations or deletions, were visible on light microscopy. These chromosomal and molecular deletions are likely to be related to the loss of a tumor-suppressor gene (or genes) located on 9p, which may be an interferon gene or an unrelated but closely linked gene.