bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the biomechanical properties of neutrophils and endothelial cells during adhesion
Authors: Wang Qin , Chiang Eddie T. , Lim Mark , Lai Jean , Rogers Rick , Janmey Paul A. , Shepro David , Doerschuk Claire M.
Published: July 2002

This study examined changes in the biomechanical properties of cultured pulmonary microvascular endothelial cells (ECs) and neutrophils induced by adhesion of neutrophils to these ECs. The biomechanical properties of cells were evaluated using magnetic twisting cytometry, which measures the angular rotation of ferromagnetic beads bound to cells through antibody ligation on application of a specified magnetic torque. Adhesion of neutrophils to 24-hour tumor necrosis factor-α (TNF-α)–treated ECs, but not to untreated ECs, induced an increase in EC stiffness within 2 minutes, which was accompanied by an increase and a reorganization of F-actin in ECs. A cell-permeant, phosphoinositide-binding peptide attenuated the EC stiffening response, suggesting that intracellular phosphoinositides are required. The stiffening response was not inhibited by ML-7, a myosin light-chain kinase inhibitor, or BAPTA, an intracellular Ca2+ chelator. Moreover, the phosphorylation pattern of the regulatory myosin light chains was unaltered within 15 minutes of neutrophil adherence. These data suggested that the EC stiffening response appeared not to be mediated by myosin light-chain–dependent mechanisms. Concomitantly, neutrophil adhesion to 24-hour TNF-α–treated ECs also induced changes in the biomechanical properties of neutrophils compared to neutrophils bound to untreated ECs. Taken together, these results demonstrated that neutrophil adhesion to TNF-α–treated ECs induces changes in the biomechanical properties of both cell types through actin cytoskeletal remodeling. These changes may modulate neutrophil transmigration across the endothelium during inflammation.
Assessment of mechanism of acquired skewed X inactivation by analysis of twins
Authors: Vickers Mark A. , McLeod Ewan , Spector Timothy D. , Wilson Ian J.
Published: July 2002

Skewed X-chromosome inactivation in peripheral blood granulocytes becomes more frequent with increasing age, affecting up to half of those over 75 years old. To investigate the mechanisms underlying this phenomenon, X-inactivation profiles in 33 monozygotic and 22 dizygotic elderly twin pairs were studied. Differential methylation-sensitive restriction enzyme cutting at a hypervariable locus in the human androgen receptor gene (HUMARA) was studied on purified granulocytes using T cells as controls. A large genetic effect on skewed granulocytic X inactivation was shown (P < .05); heritability was estimated to be 0.68. A minor part (SD .0151 relative allele frequency [ie, larger/smaller] units) of the observed variance is due to experimental error. A further contributor to acquired skewing is stochastic asymmetric stem cell division, which was modeled and shown as unlikely to account for a substantial part of variance. Two monozygotic twin pairs had X-inactivation ratios skewed markedly in opposite directions, evidence for a further stochastic mechanism, suggestive of a single overrepresented clone. In conclusion, all 3 suggested mechanisms contribute to acquired X inactivation but the dominant mechanism is genetic selection. The observed proportion of putatively clonal hematopoiesis is similar to the lifetime incidence of hematopoietic stem cell malignancy consistent with the concept that clonal hematopoiesis precedes stem cell malignancy.
Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells
Authors: Hinz Michael , Löser Peter , Mathas Stephan , Krappmann Daniel , Dörken Bernd , Scheidereit Claus
Published: July 2002

Constitutively activated nuclear factor (NF)-κB is observed in a variety of neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF-κB for H/RS cell viability, NF-κB–dependent target genes were searched for by using adenoviral expression of the super-repressor IκBΔN. A surprisingly small but characteristic set of genes, including the cell-cycle regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1, and Bcl-xL, and the cell surface receptors CD86 and CD40 were identified. Thus, constitutive NF-κB activity maintains expression of a network of genes, which are known for frequent, marker-like expression in primary or cultured H/RS cells. Intriguingly, CD40, which is able to activate CD86 or Bcl-xL via NF-κB, is itself transcriptionally regulated by NF-κB through a promoter proximal binding site. NF-κB inhibition resulted in massive spontaneous and p53-independent apoptosis, which could be rescued by ectopic expression of Bcl-xL, underscoring its dominant role in survival of H/RS cells. Hence, NF-κB controls a signaling network in H/RS cells, which promotes tumor cell growth and confers resistance to apoptosis.
The contribution of NF-κB activity to spontaneous proliferation and resistance to apoptosis in human T-cell leukemia virus type 1 Tax-induced tumors
Authors: Portis Toni , Harding John C. , Ratner Lee
Published: July 2002

Human T-cell leukemia virus type I is the etiologic agent of adult T-cell leukemia/lymphoma. The Tax protein of this virus is thought to contribute to cellular transformation and tumor development. In this report, we have used a Tax transgenic mouse model of tumorigenesis to study the contribution of nuclear factor (NF)-κB activity to spontaneous tumor cell proliferation and resistance to apoptosis. We have demonstrated elevated expression levels of NF-κB–inducible cytokines, including interleukin (IL)-6, IL-10, IL-15, and interferon (IFN)-γ, in freshly isolated primary tumors from Tax transgenic mice. Inhibitors of NF-κB activity, sodium salicylate and cyclopentenone prostaglandins (prostaglandin A1 and 15-deoxy-Δ(12,14)-prostaglandin J2), blocked spontaneous proliferation of Tax transgenic mouse spleen cells. In addition, Tax-induced tumor cells, which are resistant to irradiation-induced apoptosis, became sensitive to apoptosis in the presence of sodium salicylate and prostaglandins. These results strongly suggest that Tax-mediated induction of NF-κB activity contributes to tumorigenesis in vivo.
Mpl ligand prevents lethal myelosuppression by inhibiting p53-dependent apoptosis
Authors: Pestina Tamara I. , Cleveland John L. , Yang Chunying , Zambetti Gerard P. , Jackson Carl W.
Published: July 2002

A single dose of Mpl ligand (Mpl-L) given immediately after lethal DNA-damaging regimens prevents the death of mice. However, the mechanism of this myeloprotection is unknown. The induction of p53-dependent apoptosis in response to DNA damage signals suggests that immediate administration of Mpl-L may inhibit p53-dependent apoptosis. This hypothesis was tested by administering a single injection of pegylated murine Megakaryocyte Growth and Development Factor (PEG-rmMGDF, a truncated recombinant Mpl-L) top53−/−and wild-type mice immediately after carboplatin (80 mg/kg) and 7.5 Gy total body γ-irradiation. PEG-rmMGDF was required to prevent the death of wild-type mice, whereas p53−/−mice survived with or without the exogenous cytokine. The degree of platelet depression and subsequent recovery was comparable in p53−/−mice to wild-type animals given PEG-rmMGDF. Hence, either Mpl-L administration or p53-deficiency protected multipotent hematopoietic progenitors and committed megakaryocyte precursors. The myelosuppressive regimen induced expression of p53 and the p53 target, p21Cipl in wild-type bone marrow, indicating that Mpl-L acts downstream of p53 to prevent apoptosis. Constitutive expression of the proapoptotic protein Bax, was not further increased. Bax−/− mice survived the lethal regimen only when given PEG-rmMGDF; however, these Bax−/−mice showed more rapid hematopoietic recovery than did identically-treated wild-type mice. Therefore, administration of Mpl-L immediately after myelosuppressive chemotherapy or preparatory regimens for autologous bone marrow transplantation should prevent p53-dependent apoptosis, decrease myelosuppression, and reduce the need for platelet transfusions.
Roles of tumor necrosis factor-α receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome
Authors: Carballo Ester , Blackshear Perry J.
Published: July 2002

Tristetraprolin (TTP) is a member of the CCCH tandem zinc-finger class of proteins. It can bind to and destabilize mRNAs encoding tumor necrosis factor-α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, mice deficient in TTP develop a complex syndrome characterized by cachexia, myeloid hyperplasia, and joint and skin inflammation. Studies using anti–TNF-α neutralizing antibodies demonstrated that this syndrome, at least in part, is a consequence of the excess production of TNF-α in the absence of TTP. To evaluate the role played by each TNF-α receptor in the pathogenesis of this syndrome, mice were generated that were deficient in TTP and either or both of the known TNF-α receptors (TNFRs), type 1 (TNFR1) and type 2 (TNFR2). Mice deficient in TTP and TNFR1, or in TTP and both receptors, were protected from developing the TNF-α–induced cachexia and inflammation. In contrast, mice deficient in TNFR2 were more severely affected than mice deficient in TTP alone, suggesting that TNFR2 might play a protective role in the development of the syndrome. In cultured cells derived from these mice, apparent cooperation between the TNFRs was required to achieve normal TNF-α–induced expression of TTP, TNF-α, and GM-CSF mRNAs. Finally, the results showed that TNFR1 plays an important role in mediating TNF-α–induced changes in TNF-α and GM-CSF mRNA stability.
Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets
Authors: Cicmil Milenko , Thomas Joanne M. , Leduc Mireille , Bon Cassian , Gibbins Jonathan M.
Published: July 2002

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the recruitment of signaling proteins that bind by way of Src-homology domain 2 interactions. Proteins that have been implicated in the negative regulation of cellular activation by ITIM-bearing receptors include the tyrosine phosphatases SHP-1 and SHP-2. Tyrosine phosphorylation of immunoreceptor tyrosine-based activatory motif (ITAM)–bearing receptors such as the collagen receptor GPVI-Fc receptor γ-chain complex on platelets leads to activation. Increasing evidence suggests that ITIM- and ITAM-containing receptors may act antagonistically when expressed on the same cell. In this study it is demonstrated that cross-linking PECAM-1 inhibits the aggregation and secretion of platelets in response to collagen and the GPVI-selective agonist convulxin. In these experiments thrombin-mediated platelet aggregation and secretion were also reduced, albeit to a lesser degree than for collagen, suggesting that PECAM-1 function may not be restricted to the inhibition of ITAM-containing receptor pathways. PECAM-1 activation also inhibited platelet protein tyrosine phosphorylation stimulated by convulxin and thrombin; this was accompanied by inhibition of the mobilization of calcium from intracellular stores. These data suggest that PECAM-1 may play a role in the regulation of platelet function in vivo.
DNA-dependent adenosine triphosphatase (helicaselike transcription factor) activates β-globin transcription in K562 cells
Authors: Mahajan Milind C. , Weissman Sherman M.
Published: July 2002

Correct developmental regulation of β-like globin gene expression is achieved by preferential transcription of a gene at a given developmental stage, silencing of other β-like gene promoters, and competition among these promoters for interaction with the locus control region (LCR). Several evolutionarily conserved DNA elements in the promoters of the β-like genes and LCR have been studied in detail, and the role of their binding factors has been investigated. However, the β-globin promoter includes additional evolutionarily conserved sequences of unknown function. The present study examined the properties of a 21-base pair (bp) promoter-conserved sequence (PCS) located at positions −115 to −136 bp relative to the transcription start site of the β-globin gene. A helicaselike transcription factor (HLTF) belonging to the SWI2/SNF2 family of proteins binds to the PCS and a partly homologous sequence in the enhancer region of the LCR hypersensitive site 2 (HS2). Elevation of the level of HLTF in K562 erythroleukemic cells increases β-promoter activity in transient transfection experiments, and mutations in the PCS that remove HLTF-binding regions abolish this effect, suggesting that HLTF is an activator of β-globin transcription. Overexpression of HLTF in K562 cells does not affect the endogenous levels of γ- and ε-globin message, but it markedly activates β-globin transcription. In conclusion, this study reports a transcription factor belonging to the SWI2/SNF2 family, which preferentially activates chromosomal β-globin gene transcription and which has not previously been implicated in globin gene regulation.
Liposomal amphotericin B (AmBisome) compared with amphotericin B ± FMLP induces significantly less in vitro neutrophil aggregation with granulocyte–colony-stimulating factor/dexamethasone–mobilized allogeneic donor neutrophils
Authors: Sulis Maria Luisa , Van de Ven Carmella , Henderson Theresa , Anderson Lauren , Cairo Mitchell S.
Published: July 2002

Concomitant use of allogeneic donor granulocyte transfusions and amphotericin B in febrile neutropenic recipients may be limited by the increased incidence of respiratory distress. In vitro effects of amphotericin B and AmBisome were compared on polymorphonuclear leukocyte (PMN) aggregation from PMNs isolated from granulocyte–colony-stimulating factor (G-CSF)/dexamethasone–mobilized allogeneic donors. Six allogeneic donors were mobilized with G-CSF (600 μg subcutaneously) and dexamethasone (8 mg orally) 12 hours before leukopheresis. AmBisome was associated with significantly less PMN aggregation (100 μM [μg/mL]) (0.33% ± 0.33% vs 54.33% ± 5.82%; P < .001) than amphotericin B. Furthermore, with the addition of the PMN agonist, FMLP, AmBisome was also associated with significantly less aggregation (100 μM [μg/mL]) (18.67% ± 1.45% vs 54.67% ± 2.4%;P < .001). In summary, these studies demonstrate that liposomal amphotericin is associated with significantly less in vitro PMN aggregation than amphotericin B and could possibly be administered concomitantly with mobilized allogeneic PMN infusions.
Parameters affecting the low-force frictional characteristics of fabrics in automated handling systems
Authors: Taylor P. M. , Bicker R. , Abbott P. J. , Pollet D. M.
Published: July 2002

Much research has been carried out on the automation of garment assembly but, in practice, many of the techniques suffer from unreliability. In order to investigate why this is so, it is necessary to determine the critical mechanical properties on the fabrics under the conditions that will be found in the handling equipment. This paper concentrates on the frictional properties of fabrics against engineering materials with particular emphasis on these properties under zero applied normal loads, i.e., self-weight. Several tests are described and the main results given. These highlight the importance of humidity and the strong in‘uence of the fabric structure and the supporting surface on the frictional characteristics. It is concluded that either the assembly must be carried out using well defined fabrics and a degree of climate control or that these effects must be carefully considered in the design of handling systems.
The influence of woven stretch fabric properties on garment design and pattern construction
Authors: Tsai I-Chin D. , Cassidy Carol , Cassidy Tom , Shen Jinsong
Published: July 2002

Tensile properties of various woven stretch fabrics were measured. The extension, residual extension and elastic recovery under repeated tests were evaluated. The measurement of a female body was taken in five different postures and five patterns produced. These were combined to produce one pattern which allows for optimum movement. This pattern was then modified by taking into account the extension and recovery properties of the stretch woven fabric. Garments produced using a traditional method of pattern production and the new modified pattern for both woven and woven stretch fabrics were compared by 40 experienced fashion and textile designers with regard to appearance and visual fit during movement.
An overview of the University of Louisiana robotic gripper system project
Authors: Kolluru Ramesh , Valavanis Kimon P. , Smith Stanford , Tsourveloudis Nikos
Published: July 2002

This paper summarizes a concluded 5-year funded research project (1994-1999) addressing the automated handling and manipulation of limp material, without distortion, deformation or damage. A series of prototype gripper systems (fixed-dimensioned and reconfigurable) were developed and integrated with Adept Series manipulators to demonstrate the gripper applicability to the textiles and apparel industry. A sensor-based control system based on the hierarchical control architecture paradigm (Valavanis and Saridis, Intelligent robotic systems: theory, design and applications, Kluwer, Amsterdam, 1992) controlled the operation of the integrated robotic gripper system. The research concluded with the conceptual and theoretical design of a reconfigurable robotic gripper system (RGS) followed by simulation-based design parameter validation, controlled by a fuzzy logic controller (for both position- and suction-based control). RGS simulation studies demonstrated the distortion-free manipulation of limp material panels of a variety of shapes and sizes.
The influence of peer feedback on self- and peer-assessment of oral skills
Authors: Patri Mrudula
Published: July 2002

This article investigates the agreement amongst teacher-, self- and peer-assessments of students in the presence of peer feedback. This is done in the context of oral presentation skills of first year undergraduate students of ethnic Chinese background. The research instrument consisted of a self- and peer-assessment questionnaire containing 14 items related to the organization of the presentation content, use of language and interaction with the audience. The participants had taken part in a training and practice session on self- and peer-assessment before engaging in the assessment tasks. The findings show that, when assessment criteria are firmly set, peer-feedback enables students to judge the performance of their peers in a manner comparable to those of the teachers. However, the same is not found to be true with self-assessment.
Review of ventricular rupture: key concepts and diagnostic tools for success
Authors: Davis Nicholas , Sistino Joseph J
Published: July 2002

Although a rare complication of acute myocardial infarction (AMI), ventricular rupture is a serious event associated with significant mortality and morbidity. Patients normally present with hemodynamic instability, often in cardiogenic shock. Despite improvements in surgical techniques and diagnostic tools, post-myocardial infarction ventricular rupture remains a difficult therapeutic challenge. There are three categories of ventricular rupture: free wall rupture (FWR), ventricular septal rupture (VSR), and papillary muscle rupture (PWR). The incidence of FWR occurs following up to 10% of myocardial infarctions. VSR and PWR have a lower incidence of 1-2% and 0.5-5%, respectively. Patients often present with single-vessel coronary artery disease and usually do not have a positive history for a previous myocardial infarction. The incidence of post infarction angina in these patients is significantly greater than in patients without ventricular rupture. Delay in treatment and continued physical activity post infarction increases the risk of ventricular rupture. Diagnostic tools such as two-dimensional echocardiography and cardiac catheterization confirm the diagnosis of ventricular rupture in only 45-88% of cases. Knowledge of the disease progression is necessary to insure accurate and timely diagnosis. Due to the rapid deterioration of these patients, there is a 50-80% mortality rate within the first week if untreated. With surgical correction, patients can extend their 5-year survival rates to 65%. A good example of the complex course of ventricular rupture is the case of a 71-year-old patient at our institution. The patient presented in cardiogenic shock following an AMI. Preoperative diagnosis was unsuccessful in determining the extent of the ventricular rupture. The correct diagnosis was determined in the operating room, and both a mitral valve replacement and closure of a ventricular septal defect were completed. The patient was successfully treated with this difficult pathology.
Measuring nursing needs of stroke patients in clinical rehabilitation: a comparison of validity and sensitivity to change between the Northwick Park Dependency Score and the Barthel Index
Authors: Post M WM , Visser-Meily J MA , Gispen L SF
Published: July 2002

Objective: To compare the content and convergent validity and the sensitivity to change of the Northwick Park Dependency Score (NPDS) to that of the Barthel Index in patients with stroke.

Setting: Rehabilitation Centre De Hoogstraat, Utrecht, The Netherlands.

Design: Inclusion of consecutive patients with stroke. Measurements at admission and every four weeks until ”nal measurement at discharge. Administration by nurses of NPDS, Barthel Index and nurses' global ratings of nursing dependency.

Results: Thirty-one patients were included and 123 measurements were obtained. Median Barthel Index scores at admission and discharge were 11.2 and 17.8 respectively. At discharge, 58.6% of all patients obtained the best possible Barthel Index score, against 31.1% for the Basic Care Needs section and 87.1% for the Special Nursing Needs sections of the NPDS. Spearman correlations between NPDS and Barthel Index were very strong (0.82–0.92) at each measurement. Both the NPDS and the Barthel Index showed strong relationships with the global rating of nursing dependency (–0.82 and 0.70 respectively) and showed good sensitivity to change, Z-values for differences between admission and discharge were 4.06 ( p < 0.001) for the NPDS and 4.20 ( p < 0.001) for the Barthel Index. Most (9/12) nurses involved in this study judged the NPDS to provide better, more precise and complete information about the actual need for care of the patients.

Conclusions: Validity and sensitivity to change of the NPDS were not superior to those of the Barthel Index but most nurses preferred the NPDS for future use.
Percutaneous endoscopic gastrostomy feeding in a district rehabilitation service
Authors: Thomson M A , Carverand A D , Sloan R L
Published: July 2002

Objectives: To examine gender, diagnosis, age, reasons for feeding, nutritional status, complications, outcome and duration of feeding in patients who have required a percutaneous endoscopic gastrostomy (PEG) for nutritional support at a district rehabilitation unit in the six years since the service was established. To identify potential for improvements in the management of future patients.

Design: Retrospective case note review of cases from 1992 to 1998.

Setting: District rehabilitation service for ages 16–64 serving the population of Fife, Scotland (population circa 350 000).

Subjects: All patients ( n = 42) who had been fed via a PEG feeding tube in the previous six years.

Results: Forty-four PEG tube insertions had been conducted for 43 episodes of feeding in 42 patients. Five episodes of feeding were because of persistent vegetative state or low awareness state and 38 because of neurological swallowing impairment. Twenty-six (60%) patients were nutritionally depleted when PEG feeding was commenced. Twenty-seven (64%) patients experienced minor complications and 15 (34%) had no complications. At three months post procedure four (9.5%) patients had died and 21 (50%) had been discharged home. The mean duration of feeding on 31 October 1998 of the 20 patients (48%) who continued feeding at that date was 3.19 ± 1.89 (mean ± SD) years.

Conclusions: Patients requiring PEG feeding in a district rehabilitation service have a range of diagnoses and the main indication for intervention is neurological swallowing impairment. The majority of patients were nutritionally depleted when feeding commenced and the reasons for this require further investigation.
Spirituality in palliative care: opportunity or burden?
Authors: Walter T
Published: July 2002

The article questions an assumption in palliative care literature, namely that all patients have a spiritual dimension and that all staff can offer spiritual care. The article identifies spirituality as a particular kind of discourse. In late-modern Anglophone societies, this discourse arises from the experience of a particular generation and a particular segment of the population, namely those moving beyond formal religion; this segment is probably better represented among caring professionals than among dying patients. A four-fold typology of patients' approaches to religion/spirituality is developed, indicating the potential of differentiating between actual patients, rather than presuming a universal ‘search for meaning’. This alternative approach may enhance opportunities for team working and reduce the likelihood of any one member of staff feeling spiritual care to be an unwelcome burden.
Virtual medical geographies: conceptualizing telemedicine and regionalization
Authors: Cutchin Malcolm P.
Published: July 2002

Telemedicine is an innovation that is changing the geography of medical care provision. Regionalization of care is one important type of geographical change resulting from the implementation of telemedicine technology. This paper introduces a range of issues bound up with telemedicine and medical care regionalization and offers a geographical conceptualization of those issues through a synthesis of ideas from several literatures. It begins by providing a background for regionalization and telemedicine. The paper continues by examining the formation of ‘virtual’ regions and the problem of their internal integration and integration with ‘material’ regions of care. A penultimate section argues for the use of regional economic geography and territoriality as contexts for understanding the continued growth and development of telemedicine networks. As part of an overall critical challenge to the protelemedicine bias in the medical care literature, the paper ends by suggesting the development of a normative ethics by medical geographers.
The early-Holocene spread of hazel (Corylus avellana L.) in Europe north and west of the Alps: an ecological hypothesis
Authors: Tallantire P. A.
Published: July 2002

The northward spread of hazel (Corylus avellana L.) from its glacial period refuges has been studied for over a century. North of the Alps the course of its pollen curve, in both relative and absolute pollen diagrams, differs from those of other early immigrant trees. There is no long ‘tail' of low values before the marked ‘rise’ to high values. The hypothesis presented is that hazel was present as non-‘ owering trees before hand, with full pollen production setting in after a stabilization and amelioration of the climate in the early Holocene. This view is based on a comprehensive survey of all the life history stages of hazel in relation to climatic and other factors, together with indications from radiocarbon dates of the ‘rise’ phenomenon, not of arbitrary pollen percentage values, for sites north of the Alps. The regional and altitudinal differences in 14C dates, with due regard to the existence of 14C plateaux, support the hypothesis, as do other independent estimates of the early-Holocene climate in northern Europe. The role of ‘ uctuating seasonal air temperatures and precipi tation is noted and the need to consider the ecological requirements of all stages of any plant species' life history is stressed.
Late-Holocene sea-level changes in south and southwest Iceland reconstructed from littoral molluscan stratigraphy
Authors: Símonarson Leifur A. , Leifsdóttir Ólöf E.
Published: July 2002

Sediments deposited during late-Holocene rise in sea level have been found in the Stokkseyri Eyrarbakki (Flói) area of south Iceland. At Stokkseyri, marine littoral sediments containing a thermophilic intertidal faunal assemblage, mainly consisting of gastropods, bivalves and barnacles with a few polychaets, bryozoans and echinoids, have been encountered behind the present storm beach a short distance from the sea. The shell layers are up to 4 m in thickness and reach up to 6 m above the present sea level and 300 m inland. During the late-Holocene sea-level rise, the sea brought sediments and shell material from the coast into a lagoon behind the ridge where it accumulated on former bog layers, during two transgressive tendencies separated by a short regressive tendency. The ages of the two transgressive tendencies are apparently 2600-2800 and 2200-2400 'C years BP, respectively. Then, after the sea retreated, a thin soil layer formed on top of the marine series. Marine sediments of late-Holocene age containing thermophilic littoral species, which have been found in peat layers in the tidal zone of Gardskagi, Reykjanes, southwest Iceland, were deposited during a sea-level rise 3200 years ago. Thus, there are sporadic occurrences of sediments with thermophilic marine fauna of late-Holocene age along the Icelandic south and southwest coast, especially in sheltered places. The mollusc stratigraphy reveals three short periods with a rise in sea level during the late Holocene, 3200-2200 cal. years BP. The calculated sea-level index points indicate an average 'long-term' trend of sea-level rise as high as 2.11 mm/yr during this period in south and southwest Iceland. There are no indications of crustal subsidence occurring in the area at the same time.
Paradigm shifts in late-Holocene climatology?
Authors: Chambers F. M. , Brain S. A.
Published: July 2002

The climatic consequences of major increases in the concentration of atmospheric carbon dioxide were calculated over 100 years ago, but only during the last two decades have the effects of human-induced increases in various atmospheric gas concentrations become a concern of a wide range of scientists. The near-century delay between the propounding of the theory and the widespread recognition of the consequences for climate of continuing human activities implies a recent shift in either the perspectives or in the interests of researchers. Here we use citation indices to discern a major shift in the focus of research into climatic change. Scientific findings in the 1970s and early 1980s are identified as a trigger to the development of wider scientific concern over human-induced climatic warming, while the period from 1988 to 1991 at first sight appears to represent a major paradigm shift. However, it is suggested here that an inferred change in scientific emphasis was caused primarily by a combination of (1) new evidence from ocean and ice cores, particularly concerning the relationship between past atmospheric gas concentrations and climatic change; (2) the availability and application of new tools, notably a new generation of General Circulation Models (GCMs); (3) attribution of human causation for other environmental problems; (4) a changing science research agenda, driven by political and funding considerations; and (5) the contemporary recording of apparently increased 'global' temperatures, which reversed a previously recorded cooling trend. We caution that the pre-eminence and longevity of the 'global warming' thesis is vulnerable either to meteorological data that do not fit with model scenarios, or to the rise or resurrection of other notions on the primary forcing factors in climatic change. To obtain a clear perspective on late-Holocene climatic change, it will be necessary to evaluate palaeoclimate data that derive from a wide range of complementary sources-sedimentological, biological, archaeological and documentary-and to compare the magnitude, rate and frequency of past climatic changes implied in those data with recorded twentieth-century 'global' changes and projected twenty-first-century scenarios.
Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity
Authors: Martin K R , Barrett J C
Published: July 2002

ROS are diverse and abundant in biological systems. While excessive ROS production clearly damages DNA, low levels of ROS affect cell signaling particularly at the level of redox modulation. Moreover, the specific contributions of ROS to apoptosis and mitogenesis in maintenance of cell number homeostasis remains to be elucidated. ROS dose is a critical parameter in determining the ultimate cellular response; however the shape of the dose response curve is unpredictable. When cells are stimulated with ROS, cell-signaling cascades are activated. It appears that the cellular redox potential is an important determinant of cell function and interruption of redox balance may adversely affect cell function. As a result, compounds such as antioxidants may intercept critical ROS signaling molecules and both protect cells and foster pathogenesis. As a result, further study is needed to unravel the role of ROS in redox regulation and the potential outcome of antioxidant administration on cellular responses.
Defining hormesis: the necessary tool to clarify experimentally the low dose–response relationship
Authors: Carelli G , Iavicoli I
Published: July 2002

The authors comment on Calabrese and Baldwin's paper ‘Defining Hormesis’, which, to date, is the first attempt to provide a definition of hormesis that goes beyond the different interpretations of this phenomenon reported in the literature. While appreciating the effort made in this study to place hormesis in a general and at the same time specific context, the authors believe some clarifications are needed as regards the quantitative features of this phenomenon. In this connection, they speculate on whether Calabrese and Baldwin think it appropriate to include hormesis assessment criteria in the document, referring in particular to those reported in a previous paper. The authors share Calabrese and Baldwin's conclusion that future experimental models designed to study hormetic phenomena must necessarily include the time factor, which not only guarantees this phenomenon will be detected, but is also able to detect the specific type of hormesis.
A Compelling Case for Voluntarism: Britain’s Alternative Strategy, 1915-1916
Authors: Farr Martin
Published: July 2002

British strategy during the Asquith coalition 1915-16 is usually described as being a battle between ideological `voluntarists’ and `compulsionists’, with the latter prevailing as Lloyd George came to power. In fact the view held by the leading voluntarist, the chancellor of the exchequer, McKenna, was not predicated on theory but on efficiency. Moreover, such were the consequences of his warnings being ignored, Britain found itself by 1917 in a position he had predicted, being forced into employing the policies he had advocated. The difference was that by then it was not out of choice.
Informed Consent to Breaking Bad News
Authors: Rudnick Abraham
Published: July 2002

Informed consent to breaking (or waiving) bad news is an important yet neglected topic. It is distinct from informed consent to diagnosis and to treatment, and may be logically and ethically sound, provided patients are competent and that no considerable harm may be caused to others by breaking or waiving bad news to patients. This requires a differential assessment procedure in order to balance patient autonomy, benefit and justice towards others, preferably exploring patients’ values, expectations and needs with them, so that an acceptable decision can be made on whether to act on their consent to breaking or waiving bad news, or to ignore it and act on informed consent by proxy. Future study should attempt to provide a detailed characterization of procedures for attaining informed consent to breaking or waiving bad news, and to test their success in establishing ethically sound health care.
High clinical inflammatory activity prior to the development of secondary progression: a prospective 5-year follow-up study
Authors: Casanova B , Coret F , Valero C , Landete L , Pascual A , Vilchez J J
Published: July 2002

Objective: To study if there are different patterns of clinical activity - measured by the annual exacerbation rate (AER) - among relapsing-remitting multiple sclerosis (RRMS), “early” secondary multiple sclerosis (SPMS) and “late” SPMS. Methods: A prospective 5-year follow-up study in 80 MS patients has been carried out, calculating the AER and the mean expanded disability status scale (EDSS) change rate (MCR). Results: A significant difference on the AER, among RRMS, early SPMS and late SPMS, has been found. Conclusions: The SPMS has a high clinical inflammatory activity before and during its transformation from a RRMS.
The pathology of primary progressive multiple sclerosis
Authors: Brück W , Lucchinetti C , Lassmann H
Published: July 2002

The present review will focus on the current knowledge of the pathology of primary progressive multiple sclerosis lesions. Multiple sclerosis (MS) is an inflammatory demyelinating disease with a broad clinical variability. The main disease courses are relapsing-remitting, secondary progressive and primary progressive MS. Pathological studies examining the specific underlying pathology of a defined clinical subtype are rare. Here, we focus on the phatological characteristics of the MS lesions and summarize the current findings of the phatology of primary progressive MS with respect to inflammation, oligodendrocyte/myelin pathology, axon destruction and immunopathology of the lesions.
A survey of the World Development Reports I: discursive strategies
Authors: Mawdsley Emma , Rigg Jonathan
Published: July 2002

This is the first of two surveys of the World Development Report series. Here we focus on the discursive strategies adopted by the Reports. We begin by setting the Reports within the wider milieu of development theory and practice. Behind the pragmatic, problem-solving image that the Reports aim to promote we identify a narrow and pre-framed position that eschews radical or alternative agendas. The Reports engage in numerous discursive ploys to undermine, ignore or manipulate other positions and establish the Reports (and, by extension, the World Bank) as the repository of development ‘common sense’. While the Reports are impressive synthesizing documents, they have lost their ability to play a truly leading role in thinking about development because of their failure to debate alternative positions or fully acknowledge the mistakes of the past.
The software industry and development: the case of India
Authors: Kambhampati Uma S.
Published: July 2002

Software and globalization provide both opportunities and challenges to developing countries. Whether these opportunities are successfully utilized depends upon the availability of infrastructure and educational skills, a conclusion arrived at by many development debates over the past few decades. We will consider the impact of the software industry on development, drawing on the case of India. We show that in India, a number of factors have come together to contribute to the success of this industry, in spite of relatively poor infrastructure and education levels. In this case, however, the inadequacy of infrastructure and education have manifested themselves in an uneven spread of the benefits of this industry, leading to enclave-type development in urban centres in the southern and western parts of the country. While this is improving, the government has to take an active role to ensure a more even spread of the benefits accruing from this industry.
From savage space to governable space: the extension of United States judicial sovereignty over Indian Country in the nineteenth century
Authors: Olund Eric N.
Published: July 2002

The ways in which Native American communities as well as American society at large are constituted today are in no small part the legacies of the Indian reform era, a period of time spanning the 1880s and 1890s during which the assimilation of Native people and their spaces into the American polity became an explicit project of US governance. This civilizing mission, however, was a double moment in American history, for not only was it intended to reconstitute ‘Indians’ as American citizens through the force of law - it also enabled a certain claim to innocence on the part of American society. In this paper, I explore ways in which the cant of conquest was transformed into the ‘gift’ of civilization through the arguments of reformers, including their appropriations of Native testimony. ‘Indians’ started to become ‘Native Americans’, citizens equal before (US) law in an ostensibly liberal polity, yet this assertion of Native equality was made on the terms of white reformers which erased colonialism from American political discourse.
Implications of Microscopic Satellites of the Primary and Extracapsular Lymph Node Spread in Patients With High-Risk Melanoma: Pathologic Corollary of Eastern Cooperative Oncology Group Trial E1690
Authors: Rao U.N.M. , Ibrahim J. , Flaherty L.E. , Richards J. , Kirkwood J.M.
Published: July 2002

PURPOSE: To correlate the presence of extracapsular spread (ECS) of regional nodal metastases, and micrometastasis near the primary tumor, with disease outcome in the intergroup study E1690 in relation to the impact of recombinant interferon-alfa (rIFNα)-2b.

PATIENTS AND METHODS: E1690 included 642 patients with American Joint Committee on Cancer stage IIB or III cutaneous melanoma. Patients were randomized into high- and low-dose rIFNα-2b treatment arms and an observation arm. Pathologic slides were reviewed for selected parameters from at least half of the subjects in all three arms. Evaluation of the primary tumor included notations regarding ulceration, mitotic activity, thickness, microscopic satellites (MS), and nodal ECS on a standardized pathology form. These data were collated in relation to relapse-free survival (RFS) and overall survival (OS) at 50 months’ follow-up and studied using Cox regression analysis.

RESULTS: Ulceration, mitotic activity, thickness, and size of tumor-bearing lymph nodes did not show a statistically significant correlation with either OS or RFS across all treatment arms. The presence of MS was correlated with RFS (P = .0008) and OS (P = .05). ECS correlated with RFS (hazard ratio = 1.44, P = .032) but not OS (P = .11).

CONCLUSION: The presence of MS (in 6% [18 of 308 patients]) had a significant adverse impact on both RFS (P = .0008) and OS (P = .053). Ulceration, mitotic activity, thickness, and number of positive lymph nodes had no significant effect on OS in this subset study (univariate or multivariate Cox analysis). The presence of ECS in lymph nodes had a significant adverse effect on RFS (P = .032) but not on OS.
US Surgeon General Vivek Murthy: Firearm Violence Is a Public Health Crisis
Authors: Abbasi Jennifer , Hswen Yulin
Published: July 2024

This Medical News article is an interview with US Surgeon General Vivek Murthy, MD, MBA, and JAMA Editor in Chief Kirsten Bibbins-Domingo, PhD, MD, MAS, about a new advisory that declares gun violence a public health crisis.
Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023
Authors: Mariani Marco , Viale Giulia , Galbardi Barbara , Licata Luca , Bosi Carlo , Dugo Matteo , Notini Giulia , Naldini Matteo M. , Callari Maurizio , Criscitiello Carmen , Pusztai Lajos , Bianchini Giampaolo
Published: July 2024

Importance

Clinical trials are the path to test and introduce new therapies in the clinic. Trials that are unable to produce results represent inefficiency in the system and may also undermine patient confidence in the new drug development process.

Objectives

To survey the immunotherapy clinical trial landscape of breast cancer between January 2004 and April 2023 and examine what fraction of trials with primary completion date up to November 30, 2022, failed to report outcome, assessing the proportion of trials that yielded positive results and describing trial features associated with these 2 outcomes.

Design, Setting, and Participants

This cross-sectional study included breast cancer immunotherapy trials identified in ClinicalTrials.gov. Trial details and results were retrieved in December 2023. Google Scholar, PubMed, and LARVOL CLIN websites were also searched for reports.

Main Outcomes and Measures

Trial outcome reported as abstract or manuscript. Reported trials were categorized as positive (ie, met its end point) or negative. Association between reporting and trial features were tested using Fisher exact test.

Results

A total of 331 immuno-oncology trials were initiated in breast cancer by April 2023; 242 trials were phase II, 47 were phase I, and 42 phase III. By setting, 212 studies (64.0%) were conducted in metastatic, 94 (28.4%) in neoadjuvant, and 25 (7.6%) in adjuvant settings. Among phase II and III trials, 168 (59.2%) were nonrandomized. One hundred twenty trials had primary completion dates up to November 30, 2022, of which 30 (25.0%; enrolling a combined 2428 patients) failed to report their outcomes; 7 phase I trials (31.8%), 21 phase II trials (23.6%), and 2 phase III trials (22.2%) were unreported. Single-center studies were significantly more likely to be unreported than multicenter studies (19 of 54 [35.2%] vs 9 of 60 [15.0%]; P = .02). Of the 90 reported trials, 47 (52.2%) and 43 (47.8%) were positive and negative, respectively. Seventeen of 19 (89.5%) of the reported randomized trials (accruing a total of 4189 patients) were negative.

Conclusions and Relevance

In this cross-sectional study of immunotherapy breast cancer trials, the large number of trials yielded modest clinical impact. Single-center trials commonly failed to report their outcomes and many phase II studies have not translated into corresponding successful phase III trials.
Combined Effect of Oxygen Vacancies and Mesopore Sizes in ZnO/SiO2 Adsorbents on Boosting the H2S Removal Efficiency in Moist Conditions
Authors: Yang Chao , Liu Zhilong , Su Zhelin , Wang Yeshuang , Liang Meisheng , Fan Huiling , Bandosz Teresa J.
Published: July 2024

While both pore sizes and oxygen vacancies benefit desulfurization on ZnO, their specific roles and the combined effect on the efficiency of this process are still unclear. To address this, ZnO‐based adsorbents with tunable mesopore sizes and concentrations of oxygen vacancies are synthesized. These two features are directly regulated through varying the carbon chain length of dihydric alcohol, which is used as a precursor in the synthesis process. They influenced the desulfurization performance through affecting the diffusion and dissociation of H2S. The sizes of mesopores determined the amounts of adsorbed water/ thickness of a water film while the amount of oxygen vacancies controlled the contents of hydroxyl groups. The latter not only are replaced by (bi)sulfide anions but also promote the dissociation of H2S through acid‐base interaction. Adsorbed water contributed to hydroxylation of the surface until the cease of desulfurization. However, too much‐adsorbed water increased the resistance of H2S diffusion through the water film to the surface of ZnO, deteriorating the performance. The optimal amounts of adsorbed water/thickness of water film and a sufficient amount of oxygen vacancies/hydroxyl groups are provided in the adsorbent with a mesopore size of ∼10 nm leading to a maximum H2S removal capacity of 151.9 mg g−1.