bluuebunny/crossref_metadata_2025 huggingface dataset:
Triad case study: Rattlesnake Creek
Authors: Johnson Robert L. , Durham Lisa A. , Rieman Craig R. , Hummel Janna E.
Published: December 2004

The U.S. Army Corps of Engineers (US ACE) is responsible for conducting the cleanup of radiological contaminated properties as part of the Formerly Utilized Sites Remedial Action Program. One property is the Rattlesnake Creek (RSC) portion of the Ashland sites. The RSC stream sediments are contaminated with thorium‐230, radium‐226, and uranium. The US ACE is closing RSC using protocols contained within the Multi‐Agency Radiation Survey and Site Investigation Manual (MARSSIM). At RSC, the US ACE developed site‐specific derived concentration guideline level (DCGL) cleanup requirements consistent with the MARSSIM guidance. Because of uncertainty about the distribution of contamination within the creek, the US ACE used the Triad approach to collect data and design remedial actions. Systematic planning helped target the areas of concern, develop a conceptual site model, and identify data gaps to be addressed before remediation plans were finalized. Preremediation sampling and analysis plans were designed to be explicitly consistent with final status survey requirements, allowing data sets to support both excavation planning needs and closure requirements in areas where contamination was not encountered above DCGL standards. Judicious use of real‐ time technologies such as X‐ray fluorescence and gamma walkover surveys minimized expensive off‐ site alpha spectrometry analyses, and at the same time provided the ability to respond to unexpected field conditions. © 2004 Wiley Periodicals, Inc.
Historical analysis of monitored natural attenuation: A survey of 191 chlorinated solvent sites and 45 solvent plumes
Authors: McGuire Travis M. , Newell Charles J. , Looney Brian B. , Vangelas Karen M. , Sink Claire H.
Published: December 2004

A survey of experts in the application of natural attenuation was conducted to better understand how monitored natural attenuation (MNA) is being applied at chlorinated solvent sites. Thirty‐four remediation professionals provided general information for 191 sites where MNA was evaluated, and site‐specific data for 45 chlorinated solvent plumes being remediated by MNA. Respondents indicated that MNA was precluded as a remedy at only 23 percent of all sites where evaluated as a remedial option. Leading factors excluding MNA as a remedial approach were the presence of an expanding plume and an unreasonably long estimated remediation time frame. MNA is being used as the sole remedy at about 30 percent of the sites, and 33 percent are implementing MNA in conjunction with source zone remediation. The remaining sites are implementing MNA with plume remediation (13 percent), source containment (9 percent), or some other strategy (16 percent). © 2004 Wiley Periodicals, Inc.
Sequential Synthesis of Type II Colloidal CdTe/CdSe Core–Shell Nanocrystals
Authors: Yu Kui , Zaman Badruz , Romanova Svetlana , Wang Da‐shan , Ripmeester John A.
Published: December 2004

Colloidal type II CdTe/CdSe nanocrystals were synthesized by sequential addition of a tri‐n‐octylphosphine telluride (TOPTe)/TOP solution and several shell‐precursor solutions to a CdO/TOP solution; the shell‐precursor solutions consisted of CdO and TOPSe in TOP. For the growth of the CdTe core, the TOPTe/TOP solution was swiftly added to the CdO/TOP solution at a higher temperature (300 °C) than the growth temperature (250 °C). For the growth of the CdSe shell, in contrast, the CdO/TOPSe/TOP solution was slowly added to the CdTe/TOP solution at a lower temperature than the growth temperature (200–240 °C). The temporal evolution of the optical properties of the growing core–shell nanocrystals was monitored in detail. During the growth of the CdSe shell, the core–shell nanocrystals exhibited interesting changes in photoluminescence (PL) properties. The highest PL efficiency (≈38 %) was detected from core–shell nanocrystals with a CdSe shell thickness of 0.4–0.5 nm (indicated by TEM); the formation of the first monolayer is proposed. Our synthetic approach is well suited to a practical realization of engineering materials with bandgaps in the near‐IR and IR spectral ranges.
Dyskeratosis congenita: molecular insights into telomerase function, ageing and cancer
Authors: Marrone Anna , Dokal Inderjeet
Published: December 2004

Dyskeratosis congenita (DC) is a severe, inherited, bone marrow failure syndrome, with associated cutaneous and noncutaneous abnormalities. DC patients also show signs of premature ageing and have an increased occurrence of cancer. DC can originate through: (1) mutations in DKC1, which result in X-linked recessive DC; (2) mutations in the RNA component of telomerase (TERC), which result in autosomal dominant DC (AD-DC); and (3) mutations in other, currently uncharacterised, genes, which result in autosomal recessive DC (AR-DC). As DKC1 encodes dyskerin, a protein component of small nucleolar ribonucleoprotein (snoRNP) particles, which are important in ribosomal RNA processing, DC was initially described as a disorder of defective ribosomal biogenesis. Subsequently, dyskerin and TERC were shown to closely associate with each other in the telomerase complex, and DC has since come to be regarded as a telomerase deficiency disorder characterised by shorter telomeres. These findings demonstrate the importance of telomerase in humans and highlight how its deficiency (through DKC1 and TERC mutations) results in multiple abnormalities including premature ageing, bone marrow failure and cancer. Identification of the gene(s) involved in AR-DC will help to define the pathophysiology of DC further, as well as expand our insights into telomere function, ageing and cancer.
Warm ocean is eroding West Antarctic Ice Sheet
Authors: Shepherd Andrew , Wingham Duncan , Rignot Eric
Published: December 2004

Satellite radar measurements show that ice shelves in Pine Island Bay have thinned by up to 5.5 m yr−1 over the past decade. The pattern of shelf thinning mirrors that of their grounded tributaries ‐ the Pine Island, Thwaites and Smith glaciers ‐ and ocean currents on average 0.5°C warmer than freezing appear to be the source. The synchronised imbalance of the inland glaciers is the result of reduced lateral and basal tractions at their termini, and the drawdown of grounded ice shows that Antarctica is more sensitive to changing climates than was previously considered.
Diagnosing the role of eddies in driving the circulation of the northwest Atlantic Ocean
Authors: Zhai Xiaoming , Greatbatch Richard J. , Sheng Jinyu
Published: December 2004

In this letter we present a variation of the recently proposed “semi‐prognostic method” for use with ocean models. The new version has the advantage that model drift is effectively prevented, while at the same time the meso‐scale eddy field is free to evolve. We use the method to probe the importance of the eddy‐driven circulation in the northwest Atlantic Ocean. For the particular model we use here, it is shown that the eddies strongly reinforce the eastward Gulf Stream jet and the northern recirculation in the slope region, with over 50% of the total transport of this recirculation being directly eddy‐driven. The eddies also play a role in setting the temperature and salinity properties of the “northwest corner” southeast of Newfoundland.
A late Pleistocene–Holocene noble gas paleotemperature record in southern Michigan
Authors: Ma Lin , Castro Maria Clara , Hall Chris Michael
Published: December 2004

Noble gas temperatures (NGTs) and 14C derived ages in groundwaters of the Michigan Basin reveal a ground temperature of ∼1°C toward the end of the Last Glacial Maximum (LGM) suggesting that groundwater recharge occurred under the Laurentide Ice Sheet (LIS) cover. In addition to the general warming observed since the LGM, the NGT record indicates an abrupt warming event between ∼12.8 and 11.1kyrs BP, correlative to the Bølling‐Allerød (BOA) warm phases. Ice‐sheet‐linked changes in freshwater delivery to the North Atlantic, together with changes in the North Atlantic Deep Water (NADW) circulation are possible causes of such abrupt climate shifts in northeastern US. Pleistocene waters yielding the lowest NGTs have the highest δ18O and δD values, suggesting an atmospheric circulation pattern distinct from today, with a stronger moisture component from the Gulf of Mexico, possibly due to the presence of the LIS which weakened the Pacific westerly flow.
Barotropic tides in the South Atlantic Bight
Authors: Blanton Brian O. , Werner Francisco E. , Seim Harvey E. , Luettich Richard A. , Lynch Daniel R. , Smith Keston W. , Voulgaris George , Bingham Frederick M. , Way Francis
Published: December 2004

The characteristics of the principal barotropic diurnal and semidiurnal tides are examined for the South Atlantic Bight (SAB) of the eastern United States coast. We combine recent observations from pressure gauges and ADCPs on fixed platforms and additional short‐term deployments off the Georgia and South Carolina coasts together with National Ocean Service coastal tidal elevation harmonics. These data have shed light on the regional tidal propagation, particularly off the Georgia/South Carolina coast, which is perforated by a dense estuary/tidal inlet complex (ETIC). We have computed tidal solutions for the western North Atlantic Ocean on two model domains. One includes a first‐order representation of the ETIC in the SAB, and the other does not include the ETIC. We find that the ETIC is highly dissipative and affects the regional energy balance of the semidiurnal tides. Nearshore, inner, and midshelf model skill at semidiurnal frequencies is sensitive to the inclusion of the ETIC. The numerical solution that includes the ETIC shows significantly improved skill compared to the solution that does not include the ETIC. For the M2 constituent, the largest tidal frequency in the SAB, overall amplitude and phase error is reduced from 0.25 m to 0.03 m and 13.8° to 2.8° for coastal observation stations. Similar improvement is shown for midshelf stations. Diurnal tides are relatively unaffected by the ETIC.
Dissolution, speciation, and reaction of acetaldehyde in cold sulfuric acid
Authors: Michelsen Rebecca R. , Ashbourn Samantha F. M. , Iraci Laura T.
Published: December 2004

The uptake of gas‐phase acetaldehyde [CH3CHO, ethanal] by aqueous sulfuric acid solutions was studied under upper tropospheric/lower stratospheric (UT/LS) conditions. The solubility of acetaldehyde was found to be low, between 2 × 102 M atm−1 and 1.5 × 105 M atm−1 under the ranges of temperature (211–241 K) and acid composition (39–76 weight percent, wt%, H2SO4) studied. Under most conditions, acetaldehyde showed simple solubility behavior when exposed to sulfuric acid. Under moderately acidic conditions (usually 47 wt% H2SO4), evidence of reaction was observed. Enhancement of uptake at long times was occasionally detected in conjunction with reaction. The source of these behaviors and the effect of acetaldehyde speciation on solubility are discussed. Implications for the uptake of oxygenated organic compounds by tropospheric aerosols are considered.
A polarized discrete ordinate scattering model for simulations of limb and nadir long‐wave measurements in 1‐D/3‐D spherical atmospheres
Authors: Emde C. , Buehler S. A. , Davis C. , Eriksson P. , Sreerekha T. R. , Teichmann C.
Published: December 2004

This article describes one of the scattering algorithms of the three‐dimensional polarized radiative transfer model ARTS (Atmospheric Radiative Transfer Simulator) which has been implemented to study for example the influence of cirrus clouds on microwave limb sounding. The model uses the DOIT (Discrete Ordinate Iterative) method to solve the vector radiative transfer equation. The implementation of a discrete ordinate method is challenging due to the spherical geometry of the model atmosphere which is required for the simulation of limb radiances. The involved numerical issues, which are grid optimization and interpolation methods, are discussed in this paper. Scattering simulations are presented for limb‐ and down‐looking geometries, for one‐dimensional and three‐dimensional spherical atmospheres. They show the impact of cloud particle size, shape, and orientation on the brightness temperatures and on the polarization of microwave radiation in the atmosphere. The cloud effect is much larger for limb radiances than for nadir radiances. Particle size is a very important parameter in all simulations. The polarization signal is negligible for simulations with completely randomly oriented particles, whereas for horizontally aligned particles with random azimuthal orientation the polarization signal is significant. Moreover, the effect of particle shape is only relevant for oriented cloud particles. The simulations show that it is essential to use a three‐dimensional scattering model for inhomogeneous cloud layers.
Analysis of hydraulic and tracer response tests within moderately fractured rock based on a transition probability geostatistical approach
Authors: Park Y.‐J. , Sudicky E. A. , McLaren R. G. , Sykes J. F.
Published: December 2004

A transition probability and Markov chain geostatistical approach is applied to synthesize the discrete permeability structure of moderately fractured rock. The approach can infuse either hard or subjective categorical information that is consistent with geological interpretations. The methodology is tested using data collected from the Moderately Fractured Rock (MFR) experiment area of the Underground Research Laboratory (URL) in southeastern Manitoba, Canada. Attributes pertaining to fracture location, frequency, and orientation along an array of boreholes intersecting the MFR experiment area, taken together with results from hydraulic response tests within packed‐off intervals along the boreholes, are used to produce conditional stochastic realizations of hydraulic conductivity and effective porosity. Using the generated hydraulic conductivity and porosity realizations, we compare predicted tracer concentrations to the results of measured breakthrough data in a stochastic framework. The results show that solute migration behavior in moderately fractured rock can be successfully characterized and reasonably predicted upon careful error analysis of the results obtained from the various medium realizations synthesized from the conditional categorical descriptions of the fractured crystalline rock.
A computationally practical approach for modeling complex mean flows in mildly heterogeneous media
Authors: Li Shu‐Guang , Liao H. S. , Ni Chuen‐Fa
Published: December 2004

We present in this paper a critical review of recent research on nonuniform mean flows in heterogeneous porous media, examine why existing stochastic methods are computationally so difficult to implement, and introduce a new and efficient alternative. Specifically, we reformulate the nonstationary spectral method of Li and McLaughlin (1991, 1995) and present a new way for its numerical implementation, combining the best advantages of efficient analytical solutions and flexible numerical techniques. The result is a substantially improved stochastic technique that allows modeling efficiently the nonlinear scale effects for moderately heterogeneous media in the presence of general nonstationarity. In particular, the reformulated approach allows computing the nonlocal and nonstationary mean “closure” flux using a coarse grid without having to resolve numerically the small‐scale heterogeneous dynamics. The methodological innovation significantly increases the size and expands the range of groundwater problems that can be analyzed with stochastic methods. The effectiveness of the new spectral approach is illustrated with two concrete examples and a systematic comparison with existing stochastic methods.
Comparison of periodontal disease status of adults in two untreated indigenous populations of Guatemala, Central America
Authors: Dowsett S. A. , Eckert G. J. , Kowolik M. J.
Published: December 2004

Objective:  To compare the periodontal disease levels of two distinct indigenous populations of Guatemala, Central America, to determine whether differences exist.

Material and methods: Cross‐sectional studies were performed in adults from the communities of San Juan La Laguna, SJLL (n = 125) and Tzununa (n = 54). In both cases, full‐mouth pocket probing depths (PPDs) and clinical attachment levels (CALs) were measured by a single examiner, and the same examiner was employed in both studies. Recession at each site was derived from PPD and CAL measures.

Results: Tooth number did not differ significantly between SJLL and Tzununa (28.0 and 27.2, respectively). With respect to periodontal disease status, the percentage of sites with PPD ≥ 5, 6 and 7 mm did not differ significantly, although mean PPD was significantly greater in the Tzununa sample (P = 0.01). Mean CAL and percentage of sites with CAL ≥ 4, 5, 6 and 7 mm was significantly greater in SJLL than in Tzununa (P < 0.005) and the difference increased with age. Mean recession was also significantly greater in SJLL than Tzununa (P < 0.005), as was the percentage of sites with recession ≥ 3 mm (P = 0.02), 4 mm (P = 0.002) and 5 mm (P = 0.008).

Conclusion: The disease levels differed between these two indigenous Guatemalan communities. Whether this has a primarily environmental or genetic basis remains to be elucidated.
Immunohistochemical analysis of cytokeratin and human milk fat globulin expression in mucinous carcinoma ofthe skin
Authors: Ohnishi Takamitsu , Takizawa Hajime , Watanabe Shinichi
Published: December 2004

Background:  Mucinous carcinoma of the skin (MCS) is a rare epithelial tumor which arises primarily in the skin. Metastatic MC from extracutaneous sites, especially breast or colon, mimics MCS and cannot be differentiated from MCS by routine histology alone.

Methods:  Nine cases of MCS were analyzed immunohistochemically using monoclonal antibodies against cytokeratins (CKs) and human milk fat globulin 1 (HMFG) in order to clarify their nature and compare the immunophenotypes with those of other MCs studied in the literature.

Results:  Expression of simple epithelial CKs in most of the tumor cells of all cases studied and co‐expression of simple and stratified epithelial CKs in some tumor cells of two cases were recognized. CK 20 expression could not detected in any tumor cells. Focal HMFG expression in the luminal or outer surface of the nests was observed in three cases.

Conclusion:  From CKs expression, MCS was speculated to differentiated mainly toward the secretory cells of the sweat glands, and some tumor cells toward the transient portion between the dermal duct and the secretory portion. Focal HMFG expression suggested either a consequence of malignant transformation or apocrine differentiation. No expression of CK 20 in MCS suggests that we may exclude the diagnosis of metastatic colorectal MC which expressed CK 20.
Uplift, exhumation and precipitation: tectonic and climatic control of Late Cenozoic landscape evolution in the northern Sierras Pampeanas, Argentina
Authors: Sobel Edward R. , Strecker Manfred R.
Published: December 2004

Deciphering the evolution of mountain belts requires information on the temporal history of both topographic growth and erosion. The exhumation rate of a mountain range undergoing shortening is related to the erodability of the uplifting range as well as the efficiency of erosion, which partly depends on the available precipitation. Young, rapidly deposited sediments have low thermal conductivity and are readily eroded, in contrast to underlying resistant basement rocks that have a higher thermal conductivity. Apatite fission‐track thermochronology can quantify cooling; thermal models constrain the relationship between this cooling and exhumation. By utilizing geological relations for a datum, we can examine the evolution of rock uplift, surface uplift and exhumation. In the northern Sierras Pampeanas of Argentina, a young sedimentary basin that overlay resistant crystalline basement prior to rapid exhumation provides an ideal setting to examine the effect of contrasting thermal and erosional regimes. There, tectonically active reverse‐fault‐bounded blocks partly preserve a basement peneplain at elevations in excess of 4500 m. Prior to exhumation, the two study areas were covered by 1000 and 1600 m of recently deposited sediments; this sequence begins with shallow marine deposits immediately overlying the regional erosion surface. Apatite fission‐track data were obtained from vertical transects in the Calchaquíes and Aconquija ranges. At Cumbres Calchaquíes, erosion leading to the development of the peneplain commenced in the Cretaceous, probably as a result of rift‐shoulder uplift. In contrast, Sierra Aconquija cooled rapidly between 5.5 and 4.5 Myr. At the onset of this rapid exhumation, the sediment was quickly removed, causing fast cooling, but relatively slow rates of surface uplift. Syntectonic conglomerates were produced when faulting exposed resistant bedrock; this change in rock erodability led to enhanced surface uplift rates, but decreased exhumation rates. The creation of an orographic barrier after the range had attained sufficient elevation further decreased exhumation rates and increased surface uplift rates. Differences in the magnitude of exhumation at the two transects are related to both differences in the thickness of the sedimentary basin prior to exhumation and differences in the effective precipitation due to an orographic barrier in the foreland and hence differences in the magnitude of headward erosion.
Normal fault growth and early syn‐rift sedimentology and sequence stratigraphy: Thal Fault, Suez Rift, Egypt
Authors: Young Mike J. , Gawthorpe Rob. L. , Sharp Ian R.
Published: December 2004

This paper investigates the tectono‐stratigraphic development of a major, segmented rift border fault (Thal Fault) during ca. 6 Myr of initial rifting in the Suez Rift, Egypt. The Thal Fault is interpreted to have evolved by the progressive linkage of at least four fault segments. We focus on two contrasting structural settings in its hangingwall: Gushea, towards the northern tip of the fault, and Musaba Salaama, ca. 20 km along‐strike to the south, towards the centre of the fault. The early syn‐rift stratigraphic succession passes upwards from continental facies, through a condensed marginal marine shell‐rich facies, into fully marine shoreface sandstone and offshore mudstone. Regionally correlatable stratal surfaces within this succession define time‐equivalent stratal units that exhibit considerable along‐strike variability in thickness and facies architecture. During the initial ca. 6 Myr of rifting, the thickest stratigraphy developed towards the centre of the array of fault segments that subsequently hard linked to form the Thal Fault. Thus, a displacement gradient existed between fault segments at the centre and tip of the fault array, suggesting that the fault segments interacted, and a fixed length was established for the fault array, at an early stage in rifting. Towards the centre of the Thal Fault the early syn‐rift succession shows pronounced thickening away from the fault and towards a series of intra‐block antithetic faults that were active for up to ca. 6 Myr. This indicates that a large proportion of fault‐controlled subsidence during the initial ca. 6 Myr of rifting occurred in the hangingwalls of antithetic intra‐block faults, and not the present‐day Thal Fault. The antithetic faults progressively switched off during rifting such that after ca. 6 Myr of rifting, fault‐activity had localised on the Thal Fault enabling it to accrue to the present‐day high level of displacement. Aspects of the development of the Thal Fault appear to be in contrast to many models of fault evolution that predict large‐displacement rift‐climax faults to have always had the greatest displacement during fault population evolution. This study has implications for tectono‐stratigraphic development during early rift basin evolution. In particular, we stress that caution must be taken when relating final rift‐climax fault structure to the early tectono‐stratigraphy, as these may differ considerably.
Stratigraphic signatures of translation of thrust‐sheet top basins over low‐angle detachment faults
Authors: Clevis Quintijn , De Jager Gerben , Nijman Wouter , De Boer Poppe L.
Published: December 2004

Abstract Low‐angle detachment faults and thrust‐sheet top basins are common features in foreland basins. However, in stratigraphic analysis their influence on sequence architecture is commonly neglected. Usually, only eustatic sea level and changing flexural subsidence are accounted for, and when deformation is considered, the emphasis is on the generation of local thrust‐flank unconformities. This study analyses the effects of detachment angle and repetitive detachment activation on stratigraphic stacking patterns in a large thrust‐sheet top basin by applying a three‐dimensional numerical model.

Model experiments show that displacement over low‐angle faults (2–6°) at moderate rates (∼5.0 m kyr−1) results in a vertical uplift component sufficient to counteract the background flexural subsidence rate. Consequently, the basin‐wide accommodation space is reduced, fluvio‐deltaic systems carried by the thrust‐sheet prograde and part of the sediment supply is spilled over towards adjacent basins. The intensity of the forced regression and the interconnectedness of fluvial sheet sandstones increases with the dip angle of the detachment fault or rate of displacement. In addition, the delta plain is susceptible to the formation of incised valleys during eustatic falls because these events are less compensated by regional flexural subsidence, than they would be in the absence of fault displacement.
Single‐centre experience with allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in childhood: similar survival after matched‐related and matched‐unrelated donor transplants
Authors: Al‐Kasim F. A. , Thornley I. , Rolland M. , Lau W. , Tsang R. , Freedman M. H. , Saunders E. F. , Calderwood S. , Doyle J. J.
Published: December 2004

Summary. Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)‐matched related donor (MRD). For these children, BMT from a matched unrelated donor (MUD) represents a therapeutic option. We reviewed the course of 62 children with ALL who received fully matched marrow allografts at our institution between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics were similar in the two groups. The interval from attainment of pre‐BMT complete remission to transplant was significantly longer in the MUD group. Conditioning (etoposide/total body irradiation) and graft‐versus‐host disease (GVHD) prophylaxis regimens were the same for all patients, and all received T cell‐replete bone marrow. There was no significant difference in probability of engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a significantly greater incidence of grade II–IV acute GVHD (58% versus 24% in the MRD group; P= 0·02), and demonstrated a trend towards more chronic GVHD (39% versus 15%; P= 0·06). Three years post BMT, the probabilities of transplant‐related mortality were 33 ± 11% and 20 ± 8% in MUD and MRD groups respectively (P = 0·38); the probabilities of relapse were 28 ± 12% and 41 ± 9% respectively (P = 0·19). Lansky or Karnofsky performance scores in event‐free survivors were 90–100 in 87% of the MUD group and 83% of the MRD group. With a median follow up of 38 months (range, 3–97), 3‐year event‐free survival was 49 ± 11% and 47 ± 9% in the MUD and MRD BMT groups respectively (P = 0·71). These results suggest that MUD BMT is a valuable therapy for children with ALL in whom BMT is indicated, and underscore the importance of efforts aimed at expediting unrelated donor searches for patients lacking a MRD.
Iron deficiency can upregulate expression of transferrin receptor at both the mRNA and protein level
Authors: Tong Xiangjun , Kawabata Hiroshi , Koeffler H. Phillip
Published: December 2004

Summary. Expression of the transferrin receptor (TfR) is controlled essentially by post‐transcriptional regulation, which is mediated by the interaction between iron regulatory proteins (IRPs) and iron‐responsive elements (IREs) located in the 3′‐untranslated region (UTR) of TfR mRNA. We examined whether additional controls of expression might occur by investigating the regulation of TfR in the absence of its' IREs by cloning 3′‐UTR truncated TfR cDNA (TfRΔIRE) into pcDNA3·1(+) and stably expressing it in CHO‐TRVb (Chinese Hamster Ovary, TfR variant cells, clone b) cells which have no endogenous TfR. Both the surface and the total cell TfR protein levels increased significantly after treating the stably transfected cells with the iron chelator desferrioxamine (DFO) compared with the control cells. In contrast, expression of the transferrin receptor 2 (TfR2), which was also cloned in the same vector and stably expressed in the TRVb‐CHO cells, was not regulated by iron chelation. In addition, TfR2 fused to the 3′‐UTR of TfR (TfR2‐IRE) was cloned into the same vector and stably expressed in the CHO‐TRVb cells. A comparison showed that expression of full‐length TfR and TfR2‐IRE increased by fivefold and twofold, respectively, after addition of DFO. Further experiments showed that TRVb‐CHO cells, which were stably transfected with TfRΔIRE and exposed to either normal medium or DFO, resulted in similar levels of TfR mRNA, but the TfR protein biosynthetic rate increased with iron chelation. In summary, expression of TfR in cells placed in an iron‐deficient milieu can increase by a mechanism which is independent of the IREs of TfR.
A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony‐stimulating factor: significant effects on quality of life
Authors: Hellström‐Lindberg Eva , Gulbrandsen Nina , Lindberg Greger , Ahlgren Tomas , Dahl Inger Marie S. , Dybedal Ingunn , Grimfors Gunnar , Hesse‐Sundin Eva , Hjorth Martin , Kanter‐Lewensohn Lena , Linder Olle , Luthman Michaela , Löfvenberg Eva , Öberg Gunnar , Porwit‐MacDonald Anja , Rådlund Anders , Samuelsson Jan , Tangen Jon Magnus , Winquist Ingemar , Wisloff Finn ,   for the Scandinavian MDS Group
Published: December 2004

Summary. We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S‐Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony‐stimulating factor (G‐CSF) + Epo. S‐Epo ≤ 500 U/l and a transfusion need of < 2 units/month predicted a high probability of response to treatment, S‐Epo > 500 U/l and ≥ 2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G‐CSF + Epo. The overall response rate was 42% with 28·3% achieving a complete and 13·2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0·001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0·01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48–74%) to treatment with G‐CSF + Epo. The majority of these patients have shown complete and durable responses.
Infection – an underappreciated cause of bone pain in multiple myeloma
Authors: Desikan Raman , Barlogie Bart , Sethi Rajesh , Toor Amir , Spoon Dan , Angtuaco Edward , Vanhemert Rudy , VijayaGopal Anantha , Singhal Seema , Mehta Jayesh , Jagannath Sundar , Munshi Nikhil , Zangari Maurizio , Fassas Athanassios , Tricot Guido , Anaissie Elias
Published: December 2004

Summary. Bone pain, especially back pain, is a common presenting feature of myeloma patients. We report three multiple myeloma patients with exacerbations of back pain and referred shoulder pain resulting from vertebral infections. Two patients were treated with surgery, and one patient had computerized tomography‐guided percutaneous needle aspiration for diagnostic purposes. All three patients received a prolonged course of antibiotics. Vertebral infection resolved with this treatment in all three patients without any recurrence. Previous dexamethasone therapy, together with an episode of bacteraemia, appears to be a predisposing factor for vertebral infection. Magnetic resonance imaging enabled the diagnosis in all three patients.
Lack of association of β2‐glycoprotein I polymorphisms Val247Leu and Trp316Ser with antiphospholipid antibodies in patients with thrombosis and pregnancy complications
Authors: Camilleri Raymond S. , Mackie Ian J. , Humphries Steve E. , Machin Samuel J. , Cohen Hannah
Published: December 2004

Summary. Beta2‐glycoprotein I (β2GPI) is an important target antigen for antiphospholipid antibodies (aPL) and thus β2GPI polymorphisms may influence aPL production and the development of antiphospholipid syndrome. We have studied the relationship between the Val247Leu and Trp316Ser β2GPI polymorphisms and the aPL status of 230 patients referred for aPL screening. Sixty‐one (26·5%) had persistent aPL [anticardiolipin antibodies (IgG and/or IgM), lupus anticoagulants and/or IgG anti‐β2GPI antibodies]. A comparison of the genotypic and allelic frequencies of these two polymorphisms between the Caucasian patient population and an ethnic‐matched normal control group (n = 308) showed no significant differences between aPL‐positive patients, aPL‐negative patients and the normal control group. This suggests that the Val or Leu allele at position 247 and the Trp or Ser allele at position 316 of β2GPI do not play a role in the production of aPL. There was a significantly decreased prevalence of the Ser316 allele in aPL‐negative women (n = 98) when compared with female normal control subjects (n = 249) {0·020 [95% confidence interval (CI) 0·00–0·04]vs 0·060 (95% CI 0·04–0·08), P = 0·0286}. Subgroup analysis showed no significant difference between female patients with thrombosis and female normal control subjects. Thus, the Ser316 allele may protect women from developing pregnancy complications by influencing an anticoagulant function of β2GPI via a mechanism distinct from aPL production.
Ultrasound screening for internal jugular vein thrombosis aids the detection of central venous catheter‐related infections in patients with haemato‐oncological diseases: a prospective observational study
Authors: Lordick Florian , Hentrich Markus , Decker Thomas , Hennig Michael , Pohlmann Hans , Hartenstein Reiner , Peschel Christian
Published: December 2004

Summary. To prove the hypothesis that central venous catheter‐related thrombosis and infection are associated, 43 haemato‐oncological patients with an internal jugular vein catheter underwent ultrasound screening for thrombosis every 4 d. Catheter‐related thrombosis was detected in 13/43 patients (30%). Catheter‐related infection, as defined by the U.S. Hospital Infection Control Practices Advisory Committee, was found in 14/43 patients (33%) with colonization of the catheter in two patients, exit site infection in eight patients and catheter‐related bloodstream infection in four patients. Catheter‐related thrombosis and catheter‐related infection coincided in 12 patients and were significantly correlated (Fisher's exact test, P < 0·0001). Detection of thrombosis indicated a catheter‐related infection with a superior sensitivity (86%vs 57%) and an equivalent specificity (97%) compared with the presence of clinical signs (erythema, tenderness, warmth or swelling). Neutropenia, which occurred in 32 patients, was found in 13/14 patients (93%) with a catheter‐related infection and, therefore, seemed to be an important covariate for the development of a catheter‐related infection. This study showed a close correlation between catheter‐related thrombosis and infection. Ultrasound screening for thrombosis was helpful for detecting catheter‐related infection. These findings could be clinically useful for the handling of central venous catheters in patients with an elevated risk of infectious complications.
Gemcitabine, cisplatin and methylprednisolone chemotherapy (GEM‐P) is an effective regimen in patients with poor prognostic primary progressive or multiply relapsed Hodgkin's and non‐Hodgkin's lymphoma
Authors: Chau Ian , Harries Mark , Cunningham David , Hill Mark , Ross Paul J. , Archer Caroline D. , Norman Andrew R. , Wotherspoon Andrew , Koh Dow Mu , Gill Kairen , Uzzell Maggie , Prior Yvonne , Catovsky Daniel
Published: December 2004

Summary. This study was designed to assess the efficacy and safety of gemcitabine, cisplatin and methylprednisolone (GEM‐P) for patients with relapsed or refractory Hodgkin's disease (HD) and non‐Hodgkin's lymphoma. Twenty‐one patients were treated with gemcitabine (1000 mg/m2 d 1, 8 and 15), cisplatin (100 mg/m2 d 15) and methylprednisolone (1000 mg d 1–5) given every 28 d. Of these, 20 patients were evaluable for response. The median age was 38 years (range 17–64 years). Histological subtypes were: nodular sclerosing HD (n = 10), diffuse large B cell (n = 5), T cell‐rich B cell (n = 2), follicular (n = 2), mantle cell (n = 1) and enteropathy‐associated T‐cell lymphoma (n = 1). The median remission duration prior to receiving GEM‐P was only 42 d. The overall objective response rate was 80%[95% confidence interval (CI): 56–94%], including five complete and 11 partial responses. GEM‐P induced responses in all histological subtypes, primary progressive disease and patients who had received a previous autograft. The only grade 3–4 toxicity was myelosuppression. However, no cases of febrile neutropenia or haemorrhage with thrombocytopenia were encountered. Median survival has not yet been reached and survival probability at 1 year was 60·8% (95% CI: 31·9–80·5%). In conclusion, GEM‐P is a novel combination salvage therapy for poor‐prognostic primary progressive or multiply relapsed lymphoma patients. It has clinically significant activity with a favourable toxicity profile.
T‐cell depletion with Campath‐1H ‘in the bag’ for matched related allogeneic peripheral blood stem cell transplantation is associated with reduced graft‐versus‐host disease, rapid immune constitution and improved survival
Authors: Chakrabarti Suparno , MacDonald Dorothy , Hale Geoff , Holder Kathleen , Turner Virginia , Czarnecka Halina , Thompson Jacqui , Fegan Christopher , Waldmann Herman , Milligan Donald W.
Published: December 2004

Summary. We studied the outcome of 24 peripheral blood stem cell (PBSC) graft recipients, who were T‐cell depleted (TCD) with either 20 mg (n = 14) or 10 mg (n = 10) Campath‐1H in vitro, in comparison with a retrospective cohort of 23 unmanipulated (UM) PBSC recipients. While the neutrophil engraftment was similar, the platelet engraftment occurred earlier in the TCD group (d 11 vs 14). The incidence of acute and chronic graft‐versus‐host‐disease (GVHD) was 8·7% and 4·4% in the TCD group, respectively, compared with 47·7% and 56·3% in UM group (P < 0·001). In the TCD group, 5/6 chronic myeloid leukaemia (CML) and 4/18 non‐CML patients relapsed (vs 0/6 and 3/17 in UM group, P = 0·06). All four molecular or cytogenetic relapses of CML were disease‐free survivors following donor lymphocyte infusion. There was no difference in the incidence of serious infection between the TCD and UM groups and the lymphocyte recovery at 100 d was comparable. In the TCD cohort, the lymphocyte recovery was quicker in the 10 mg Campath‐1H group. The non‐relapse mortality (19·1%vs 66·3%) and 3 year survival (73·1 vs 19·2) were improved in the TCD group (P = 0·05). Thus elimination of late mortalities related to chronic GVHD and a rapid immune reconstitution, limiting either infection or relapse related deaths, contributed to an improved outcome following T‐cell depletion with Campath‐1H ‘in the bag’.
In vitro differentiation of natural killer T cells from human cord blood CD34+ cells
Authors: Woo So‐Youn , Jung Yu‐Jin , Ryu Kyung‐Ha , Park Hae‐Young , Kie Jeong‐Hae , Im Seok‐Ah , Chung Wha‐Soon , Han Ho‐Seong , Seoh Ju‐Young
Published: December 2004

Summary. Natural killer T (NKT) cells are involved in innate immune defence and also in the regulation of adaptive immune responses. However, the development of NKT cells in vitro has not been fully characterized and culture conditions have not been fully optimized. In the present study, we found that an NKT cell fraction developed during the in vitro culture of cord blood (CB) CD34+ cells, and this was subsequently characterized both phenotypically and morphologically. CD34+ cells purified from 10 human CB were cultured in the presence of several cytokines and analysed by flow cytometry, light microscopy and electron microscopy. The NKT cell fraction, defined phenotypically (CD3+CD16+CD56+CD94+) as expressing the invariant T‐cell receptor Vα24 and Vβ11, appeared in the CD56hi fractions. Intracytoplasmic staining demonstrated that interferon‐γ and interleukin 4 (IL‐4) were detected in the CD56hi fractions. IL‐15 was essential and, in combination with either flt3‐ligand (FL) or stem cell factor (SCF), was sufficient to induce the development of NKT cells. The phenotype of the NKT cell fraction was CD45RO+CD45RA– and CD4+CD8α+. Morphologically, they were very large, with either round or oval nuclei, moderately condensed chromatins, voluminous weakly basophilic cytoplasm and various cytoplasmic granules such as dense core granules, multivesicular bodies, and intermediate form granules. When CD34+ cells purified from bone marrow (BM) were compared with those from CB, the latter were consistently more efficient at generating CD56hi NKT cell fractions. In conclusion, IL‐15 in combination with FL and/or SCF can induce the differentiation of NKT cells from human CB CD34+ cells.
Clinical manifestations associated with the aberrant expression of the soluble granulocyte–macrophage colony‐stimulating factor receptor in patients presenting with haematological malignancies
Authors: Trus Michael R. , Bordeleau Louise , Pihl Carin , McGeer Allison , Prevost Jay , Minden Mark D. , Brown Christopher B.
Published: December 2004

Summary. The receptor for granulocyte–macrophage colony‐stimulating factor (GM‐CSF) can exist as both transmembrane (tmGMRα) and soluble (solGMRα) isoforms, and the latter, is a normal constituent of human plasma. We investigated if aberrant solGMRα expression occurs in haematopoietic malignancies and whether or not solGMRα expression levels correlated with clinical presentation. Compared with the normal population, patients with acute lymphoblastic leukaemia (ALL) had low levels of solGMRα whereas clonal disorders of the myeloid lineage demonstrated higher levels of solGMRα. Patients with acute myelogenous leukaemia (AML) and high levels of solGMRα presented with a distinct clinical picture. These patients were older, predominantly belonged to the M4 and M5 French–American–British (FAB) subtypes, and they had higher white blood cell counts at presentation including myeloid precursors and myeloblasts. They often presented with either unexplained lung infiltrates or hypoxia and lower rates of microbiologically defined infections. Elevated solGMRα levels were not associated with decreased relapse‐free and overall survival in the AML population. On multivariate analysis, the correlation between elevated solGMRα levels and age, M4 and M5 FAB subtypes and decreased numbers of infections persisted. Our study is the first to describe that distinct clinical presentations are associated with aberrant solGMRα levels in haematological malignancies.
The impact of Asian descent on the incidence of acquired severe aplastic anaemia in children
Authors: McCahon Emma , Tang Keith , Rogers Paul C. J. , McBride Mary L. , Schultz Kirk R.
Published: December 2004

Summary. Previous studies have suggested an increased incidence of acquired severe aplastic anaemia in Asian populations. We evaluated the incidence of aplastic anaemia in people of Asian descent, using a well‐defined paediatric (0–14 years) population in British Columbia, Canada to minimize environmental factors. The incidence in children of East/South‐east Asian descent (6·9/million/year) and South Asian (East Indian) descent (7·3/million/year) was higher than for those of White/mixed ethnic descent (1·7/million/year). There appeared to be no contribution by environmental factors. This study shows that Asian children have an increased incidence of severe aplastic anaemia possibly as a result of a genetic predisposition.
Detection by the fluorescence in situ hybridization technique of MYC translocations in paraffin‐embedded lymphoma biopsy samples
Authors: Haralambieva Eugenia , Banham Alison H. , Bastard Christian , Delsol Georges , Gaulard Philippe , Ott German , Pileri Stefano , Fletcher Jonathan A. , Mason David Y.
Published: December 2004

Summary. The detection of chromosomal translocations by fluorescence in situ hybridization (FISH) is widely performed, but very few studies have attempted to apply this technique to paraffin‐embedded routine biopsy samples. We report the analysis of paraffin sections from 36 B‐cell lymphoma biopsies for MYC translocation breakpoints by FISH. The probes consisted of multi‐YAC constructs that flanked the breakpoint region and that, therefore, separate upon a chromosomal translocation and generate split (or ‘segregated’) signals (rather than a more ambiguous ‘co‐localization’ pattern, obtained when the two partners in a hybrid gene are detected). The results were assessed by a simple approach that avoids the counting of signal numbers per nucleus and so is appropriate for use in routine practice. A total of 19 of the 36 lymphomas were scored as positive for MYC translocation and this included 16 of the 20 patients in whom classic cytogenetics had shown the presence of the (8;14) translocation (or one of its two variants). We conclude that this two‐colour ‘split‐signal’ technique based on breakpoint flanking probes can readily detect chromosomal translocations in paraffin sections. Furthermore, our results suggest that cases categorized as ‘atypical Burkitt’s/Burkitt‐like' lymphoma (at least for adult patients) are heterogeneous with respect to translocations involving the MYC oncogene, as well as immunophenotype and clinical features.
Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology
Authors: Elrod Jeffrey M. , Karnad Anand B.
Published: December 2004

Established in 1923, the Thorndike Memorial Laboratory at Boston City Hospital was the first clinical research laboratory in a municipal hospital in the United States of America. Minot and Castle, who were the second and third directors of the Laboratory, were pioneer haematologists and clinical investigators of the highest calibre who created an atmosphere at the Laboratory that would foster patient‐centred research and attract the best physician‐scientists to work and train there. The haematology research division of the Laboratory made important original contributions to the understanding of the pathophysiology of anaemia, the mechanisms of red cell and platelet destruction and the phagocytic role of the spleen, the nature of haemoglobin (normal and sickle cell), the nature of haemophilia and its therapy and the early classification of lymphoma. It contributed to the Thorndike Memorial Laboratory's worldwide reputation as a model research laboratory and established its reputation as the birthplace of modern haematology.