Showing papers by "Dartmouth College published in 1993"
TL;DR: The authors conducted double dyads interviews with marketing executives at a Japanese vendor firm and a pair of purchasing executives from a Japanese customer firm, each conducted with a double dyad pair of interviews.
Abstract: “Quadrads” (double dyads) of interviews, each conducted with a pair of marketing executives at a Japanese vendor firm and a pair of purchasing executives at a Japanese customer firm, provided data
4,271 citations
TL;DR: In this article, the authors describe a comprehensive theory of trust in market research relationships. But they do not consider the impact of trust on exchange relationships in the context of financial transactions, where trust is critical in facilitating exchange relationships.
Abstract: Building on previous work suggesting that trust is critical in facilitating exchange relationships, the authors describe a comprehensive theory of trust in market research relationships. This theor...
3,425 citations
TL;DR: A lattice Boltzmann model is developed which has the ability to simulate flows containing multiple phases and components and is highly efficient to compute on massively parallel computers.
Abstract: A lattice Boltzmann model is developed which has the ability to simulate flows containing multiple phases and components. Each of the components can be immiscible with the others and can have different mass values. The equilibrium state of each component can have a nonideal gas equation of state at a prescribed temperature exhibiting thermodynamic phase transitions. The scheme incorporated in this model is the introduction of an interparticle potential. The dynamical rules in this model are local so it is highly efficient to compute on massively parallel computers. This model has many applications in large-scale numerical simulations of various types of fluid flows.
2,719 citations
TL;DR: It is reported that patients with hyper-IgM syndrome (HIM) have a defective gp39-CD40 interaction, which suggests that a defect in gp39 is the basis of X-linked HIM.
840 citations
TL;DR: For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry, and only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results showed a 25% decrease in mortality at 10-18 years.
Abstract: Background Over the past 30 years, eight major randomized controlled trials of breast cancer screening--with mammography and/or clinical breast examination--have been conducted. Results from several trials have been updated during the past year, and initial results of three other trials have been reported. Purpose The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world's most recent clinical trial data on breast cancer screening, consider the new evidence, assess the current state of knowledge, and identify issues needing further research. Methods Investigators representing the eight randomized controlled trials of breast cancer screening in women aged 40-74 presented published and unpublished data. Evidence relating to the effectiveness of breast cancer screening in different age groups, especially women aged 40-49, was presented. Results For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry. A meta-analysis of six trials found a relative risk of 1.08 (95% confidence interval = 0.85-1.39) after 7 years' follow-up. After 10-12 years of follow-up, none of four trials have found a statistically significant benefit in mortality; a combined analysis of Swedish studies showed a statistically insignificant 13% decrease in mortality at 12 years. Only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results show a 25% decrease in mortality at 10-18 years. Statistical significance of this result is disputed, however. In women aged 50-69, all studies show mortality reductions; three of four studies show reductions of about 30% at 10-12 years after study entry. Results from two of these trials were statistically significant. Too few women over age 70 have been included in studies for adequate analysis. Conclusions For women aged 40-49, randomized controlled trials of breast cancer screening show no benefit 5-7 years after entry. At 10-12 years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50-69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening. Implications Randomized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer. However, much still needs to be learned. Periodic gatherings of scientists in the field should speed the process.
782 citations
TL;DR: Interference with gp39-CD40 interactions with the use of an antibody that blocks their interactions may have therapeutic potential in the treatment of autoimmune disease.
Abstract: The ligand for the CD40 antigen is a 39-kilodalton protein, gp39, expressed on the surface of activated CD4+ T cells and is essential for thymus-dependent humoral immunity. The role of gp39-CD40 interactions in autoimmune disease was investigated in vivo with the use of an antibody that blocks their interactions (anti-gp39). Arthritis induced in mice by immunization with type II collagen was inhibited by anti-gp39. Anti-gp39 blocked the development of joint inflammation, serum antibody titers to collagen, the infiltration of inflammatory cells into the subsynovial tissue, and the erosion of cartilage and bone. Thus, interference with gp39-CD40 interactions may have therapeutic potential in the treatment of autoimmune disease.
537 citations
TL;DR: Over the past two decades a vast new armamentarium of diagnostic techniques has revolutionized the practice of medicine and enhanced the physician's potential for understanding disease and treating patients but also create confusion that may ultimately be harmful to patients.
Abstract: Over the past two decades a vast new armamentarium of diagnostic techniques has revolutionized the practice of medicine. The entire human body can now be imaged in exquisite anatomical detail. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography routinely “section” patients into slices less than a centimeter thick. Abnormalities can be detected well before they produce any clinical signs or symptoms. Undoubtedly, these technological advances have enhanced the physician's potential for understanding disease and treating patients. Unfortunately, these technological advances also create confusion that may ultimately be harmful to patients. Consider the case of prostate cancer. Although the prevalence . . .
533 citations
Posted Content•
TL;DR: In this article, the authors examined predictions of a life-cycle simulation model, in which individuals face uncertainty regarding their length of life, earnings, and out-of-pocket medical expenditures, and imperfect insurance and lending markets.
Abstract: This paper examines predictions of a life-cycle simulation model -- in which individuals face uncertainty regarding their length of life, earnings, and out-of-pocket medical expenditures, and imperfect insurance and lending markets -- for individual and aggregate wealth accumulation. Relative to life-cycle or buffer-stock alternatives, our augmented life-cycle model better matches a variety of features of U.S. data, including: (1) aggregate wealth, (2) cross-sectional differences in wealth-age and consumption-age profiles by education group, and (3) short-run time-series co-movements of consumption and income.
461 citations
TL;DR: It is proposed that CBF beta is a non-DNA-binding subunit of CBF and does not contact DNA directly and as a result decrease the rate of dissociation of the CBF protein-DNA complex.
Abstract: Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major determinant of the thymic disease specificity of Moloney virus genetically maps to the conserved viral core motif in the Moloney virus enhancer. Point mutations introduced into the core site significantly shifted the disease specificity of the Moloney virus from thymic leukemia to erythroid leukemia (N.A. Speck, B. Renjifo, E. Golemis, T.N. Fredrickson, J.W. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We previously reported the purification of core-binding factors (CBF) from calf thymus nuclei (S. Wang and N.A. Speck, Mol. Cell. Biol. 12:89-102, 1992). CBF binds to core sites in murine leukemia virus and T-cell receptor enhancers. Affinity-purified CBF contains multiple polypeptides. In this study, we sequenced five tryptic peptides from two of the bovine CBF proteins and isolated three cDNA clones from a mouse thymus cDNA library encoding three of the tryptic peptides from the bovine proteins. The cDNA clones, which we call CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6, encode three highly related but distinct proteins with deduced molecular sizes of 22.0, 21.5, and 17.6 kDa that appear to be translated from multiply spliced mRNAs transcribed from the same gene. CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6 do not by themselves bind the core site. However, CBF beta p22.0 and CBF beta p21.5 form a complex with DNA-binding CBF alpha subunits and as a result decrease the rate of dissociation of the CBF protein-DNA complex. Association of the CBF beta subunits does not extend the phosphate contacts in the binding site. We propose that CBF beta is a non-DNA-binding subunit of CBF and does not contact DNA directly.
457 citations
TL;DR: It is demonstrated that DNase II can mediate internucleosomal DNA digestion characteristic of apoptosis following intracellular acidification, and question the premise that the Ca2+/Mg(2+)-dependent endonuclease is the only end onuclease involved in apoptosis.
432 citations
TL;DR: In this paper, the authors modeled the formation of a new electron radiation belt at about or = 25 that resulted from the Storm Sudden Commencement (SSC) of March 24, 1991 as observed by the Combined Release and Radiation Effects Satellite (CRRES) satellite.
Abstract: We model the rapid (about 1 min) formation of a new electron radiation belt at L about or = 25 that resulted from the Storm Sudden Commencement (SSC) of March 24, 1991 as observed by the Combined Release and Radiation Effects Satellite (CRRES) satellite Guided by the observed electric and magnetic fields, we represent the time-dependent magnetospheric electric field during the SSC by an asymmetric bipolar pulse that is associated with the compression and relaxation of the Earth's magnetic field We follow the electrons using a relativistic guiding center code The test-particle simulations show that electrons with energies of a few MeV at L greater than 6 were energized up to 40 MeV and transported to L about or = 25 during a fraction of their drift period The energization process conserves the first adiabatic invariant and is enhanced due to resonance of the electron drift motion with the time-varying electric field Our simulation results, with an initial W(exp -8) energy flux spectra, reproduce the observed electron drift echoes and show that the interplanetary shock impacted the magnetosphere between 1500 and 1800 MLT
TL;DR: In vivo administration of anti-gp39 dramatically reduced both primary and secondary humoral immune responses to erythrocytes and soluble protein antigens without altering responses to the T-independent type II antigen, trinitrophenyl-Ficoll.
Abstract: The ligand for CD40 has been recently identified as a 39-kd protein, gp39, expressed on the surface of activated CD4+ T helper cells (Th). In vitro, soluble CD40 and anti-gp39 have been shown to block the ability of Th to activate B cells, suggesting that gp39-CD40 interactions are important to T cell-dependent B cell activation. Here it is shown that in vivo administration of anti-gp39 dramatically reduced both primary and secondary humoral immune responses to erythrocytes and soluble protein antigens without altering responses to the T-independent type II antigen, trinitrophenyl-Ficoll. Treatment of mice for 4 d with anti-gp39 inhibited the anti-sheep red blood cell (SRBC) response for at least 3 wk and inhibited the expression of all immunoglobulin isotypes in secondary responses to the protein antigen, keyhole limpet hemocyanin. To examine the direct effect of anti-gp39 on Th function, SRBC-immune Th cells from anti-gp39-treated mice were adoptively transferred and shown to be fully capable of providing help. These results suggest that anti-gp39 treatment does not cause Th deletion or anergy. Anti-gp39 may mediate its profound immunosuppressive effects on humoral immunity by blocking gp39-CD40 interactions. Moreover, these studies establish gp39-CD40 as an important receptor-ligand pair for the targeting of therapeutic antibodies to control thymus-dependent humoral responses.
Journal Article•
TL;DR: Differences in the expression of gp39 on activated naive and memory T cells were observed, as well as differences in requirements for optimal gp39 expression on these subsets, suggesting that density of gp40 on the activated T cells plays an important role in determining effector function.
Abstract: Studies have established that gp39, the ligand for CD40, induces B cell cycle entry and is involved in the initiation of the humoral immune response. Expression of gp39 has been observed on normal, activated CD4+ T cells, activated lymph node cells; an activated Th1 clone, and an activated Th2 clone. Anti-CD3-activated CD8+ T cells did not express gp39; however, CD8+ T cells activated with PMA/ionomycin expressed gp39. The kinetics of anti-CD3-induced gp39 expression on a T cell clone and on splenic CD4+ T cells showed that gp39 was detectable at 4 h after activation, reaching maximal levels between 6 to 8 h postactivation and returning to near resting levels between 24 to 48 h. Lymphokines modulated the expression of gp39 on activated T cells. Expression of gp39 was inhibited by IFN-gamma on activated Th1, Th2, and CD4+ T cells; whereas TGF-beta inhibited gp39 expression only on the Th2 clone studied. All other lymphokines tested were without substantial effect. Differences in the expression of gp39 on activated naive and memory T cells were observed, as well as differences in requirements for optimal gp39 expression on these subsets. There are correlations between gp39 expression and effector function; however, anti-CD3-activated splenic CD4+ cells that express gp39 did not exhibit effector function. A comparison of the relative numbers of molecules of gp39 shows that activated Th1 clones express at least 20-fold the number of gp39 molecules/cell compared with activated splenic CD4+ cells. This may imply that density of gp39 on the activated T cells plays an important role in determining effector function.
TL;DR: Protein homology analysis showed that the predicted K1 protein shared homologous peptide sequences with other enzymes involved in the catalysis of acyl adenylate formation followed by acyl thioester formation and acyl transfer, indicating that K1 encodes a structural gene for ACAT.
TL;DR: Findings indicate that IRS1 functions as a docking protein for SH2 domain-containing proteins participating in signaling from the insulin receptor, and that insulin treatment of 3T3-L1 adipocytes leads to complex formation between IRS1 and Syp.
TL;DR: It is demonstrated that the rebound effect of thought suppression has an analog in the experience of somatic discomfort and that monitoring produced the most rapid recovery from the pain and that suppression produced the slowest.
Abstract: The study demonstrates that the rebound effect of thought suppression (Wegner, 1989) has an analog in the experience of somatic discomfort. During a cold-pressor pain induction, 63 Ss were instructed either to concentrate on their room at home (distraction), to pay close attention to their hand sensations (monitoring), or to remove awareness of those sensations from mind (suppression). Two min of postpressor pain ratings showed that monitoring produced the most rapid recovery from the pain and that suppression produced the slowest. Suppression also contaminated the interpretation of a subsequent somatic stimulation; later in the experimental hour, Ss who had suppressed their cold-pressor discomfort rated an innocuous vibration as more unpleasant than did other Ss. The strategies are discussed for their necessarily distinct processes of goal evaluation and their possibly differential drain on perceived coping capacities.
TL;DR: The sharp increase and wide geographic variation in radical prostatectomy rates make the evaluation of this surgical procedure a pressing issue and the rising rates among men aged 75 years and older merits special attention.
Abstract: OBJECTIVES To examine temporal trends and geographic variation in radical prostatectomy rates and short-term outcomes. DESIGN Population-based study of radical prostatectomy for the years 1984 through 1990. Poisson regression was used to estimate temporal and regional effects. SETTING The 50 states and the District of Columbia. PARTICIPANTS A 20% national sample of male Medicare beneficiaries aged 65 years or older. MAIN OUTCOME MEASURES Rate of radical prostatectomy; 30-day mortality; and major cardiopulmonary complications, vascular complications, or surgical repairs within 30 days of radical prostatectomy. RESULTS A total of 10,598 radical prostatectomies were identified. The adjusted rate of radical prostatectomy in 1990 was 5.75 times that in 1984. The relative increase was similar in all age groups. Substantial geographic variation existed in rates from 1988 through 1990: all states in the New England and Mid-Atlantic regions had rates equal to or below 60 per 100,000 male Medicare beneficiaries, while all states in the Pacific and Mountain regions had rates equal to or above 130 per 100,000. The mortality and morbidity after radical prostatectomy are not trivial for older men (aged 75 years and older)--almost 2% died and nearly 8% suffered major cardiopulmonary complications within 30 days of the operation. CONCLUSION The sharp increase and wide geographic variation in radical prostatectomy rates make the evaluation of this surgical procedure a pressing issue. The rising rate of radical prostatectomy among men aged 75 years and older merits special attention.
TL;DR: The patients thought benefit was greater when expressed in relative terms because they ignored the underlying risk of disease and assumed it was one, and the “framing” of benefit in relative versus absolute terms may have a major influence on patient preference.
Abstract: Objective: To test whether a patient’s perception of benefit is influenced by whether the benefit is presented in relative or absolute terms.
TL;DR: All 4 experiments supported the cue-familiarity hypothesis, because FKJs and TOTs were directly related to the number of presentations (and thereby the familiarity) of the cues, and little support was found for the target-retrievability hypothesis.
Abstract: Four experiments contrasted the cue-familiarity hypothesis of feeling-of-knowing judgments (FKJs) and tip-of-the-tongue feelings (TOTs) to the target-retrievability hypothesis. Familiarity of the cues was contrasted to memorability of the targets in a paired-associate design (e.g., A-B A-B, A-B A-B', A-B A-D, A-B C-D), in which the number of repetitions of the cue A terms was dissociated from the memorability of the target B terms. Little support was found for the target-retrievability hypothesis, because in none of the 4 experiments were FKJs related to target memorability. In one experiment, an omnibus retrieval hypothesis (which implicates total retrieval rather than just correct retrieval) and the cue-familiarity hypothesis produced isomorphic predictions that were borne out by the FKJ and TOT results. All 4 experiments supported the cue-familiarity hypothesis, because FKJs and TOTs were directly related to the number of presentations (and thereby the familiarity) of the cues.
TL;DR: It is concluded that central chemoreceptors are distributed at many locations within the brain stem, all within 1.5 mm of the surface, and that stimulation of a small fraction of all central che moreceptors can result in a large ventilatory response.
Abstract: We produced local tissue acidosis in various brain stem regions with 1-nl injections of acetazolamide (AZ) to locate the sites of central chemoreception. To determine whether the local acidosis res...
TL;DR: In this paper, the authors used 87Sr/86Sr ratios as a tracer of cation sources in stream water to estimate the release of Ca2+, Mg2+, K+ and Na+ owing to weathering.
Abstract: To assess the response of forests to a changing chemical environment, a means is needed for separating the total cation export from the watershed into a component derived from mineral weathering reactions and a component due to the removal of exchangeable (plant-available) cations in the soil1–3. We show that this separation may be possible by using 87Sr/86Sr ratios as a tracer of cation sources in stream water. Our measurements from a high-elevation forest ecosystem in the Adirondack mountains, New York, indicate that mineral weathering reactions contribute about 70% and soil cation-exchange reactions about 30% of annual strontium exports. Based on these results and the ratios of major cations to strontium in the local glacial till, we estimate the release of Ca2+, Mg2+, K+ and Na+ owing to weathering. The present weathering rate seems adequate to replace annual losses of cations from the total soil exchangeable pool, suggesting that the watershed is not in immediate danger of acidification from atmospheric deposition. But as our strontium isotope data indicate that 50–60% of the strontium in the organic-soil-horizon exchangeable and vegetation cation pools has an atmospheric origin, reduction of atmospheric cation inputs4 coupled with continued strong-acid anion inputs5 may result in significant depletion of this cation reservoir.
TL;DR: The hypothesis that aspirin has an antineoplastic effect in the large bowel is supported and the question of whether aspirin should be used to prevent large-bowel tumors would be best answered by a randomized controlled clinical trial specifically designed to address this issue.
Abstract: Background Epidemiological studies have indicated that aspirin consumption can lower the risk of large-bowel cancer. These studies are not entirely consistent, however, and their interpretation has been complicated by the possibility that cancer symptoms may have led patients to avoid aspirin or that aspirin may have influenced cancer diagnosis and treatment. Purpose Our purpose was to determine the effect of aspirin on risk of large-bowel neoplasms in a study in which aspirin use would not be expected to affect tumor detection and tumor-related symptoms would not likely influence aspirin use. A less complicated assessment of the relationship between aspirin and large-bowel tumors should thus be possible. Methods We studied 793 patients enrolled in a clinical trial of nutrient supplements to prevent large-bowel adenomas. Unlike invasive cancers, adenomas usually do not cause symptoms or detectable gastrointestinal bleeding; thus, adenomas are unlikely to influence aspirin use. Each patient had at least one large-bowel adenoma diagnosed and removed shortly before study entry and had been judged to be free of further tumors by colonoscopy. Use of aspirin was assessed by responses on questionnaires administered 6 and 12 months after enrollment. We performed complete colonoscopies on all patients 1 year after they entered the study and removed all polyps. Results Patients who reported taking aspirin on both questionnaires (consistent users) had a lower risk of new adenomas at their 1-year follow-up colonoscopy (odds ratio = 0.52; 95% confidence interval = 0.31-0.89) compared with patients who did not report using aspirin on either of the questionnaires. The apparent protective effect of consistent aspirin use was present among both men and women and did not appear to be influenced by the number of prior adenomas. Conclusions These data further support the hypothesis that aspirin has an antineoplastic effect in the large bowel. Nevertheless, the question of whether aspirin should be used to prevent large-bowel tumors would be best answered by a randomized controlled clinical trial specifically designed to address this issue.
TL;DR: By observing numerous living eggs from the lesser spotted dogfish Scyliorhinus canicula (L.) caught near Roscoff and reared at recorded temperatures as they developed from first cleavage to hatching, the first reasonably complete developmental table was worked out for this classical material in vertebrate embryology.
Abstract: By observing numerous living eggs from the lesser spotted dogfish Scyliorhinus canicula (L.) caught near Roscoff (France) and reared at recorded temperatures as they developed from first cleavage to hatching, the first reasonably complete developmental table was worked out for this classical material in vertebrate embryology. The successive stages, described and numbered from 1 to 34, correct and replace the incomplete stages A–Q proposed by Balfour (J.Anat. Physiol., 10:555–576,1876) and other even less complete series later published, and is unique in the inclusion of a timetable at 16°C. The stages can be identified, usually through the cleared eggshell wall, with naked eye or low magnification. This table of normal stages of Scyliorhinus can be adapted with slight modification to other chondrichthyan fishes. © 1993 Wiley-Liss, Inc.
Journal Article•
TL;DR: The results demonstrate the involvement of DNase II in apoptotic DNA digestion and suggest mechanisms of pH homeostasis as regulators of apoptosis.
Abstract: Apoptosis is a pathway of cell death characterized by internucleosomal digestion of genomic DNA. Such DNA digestion can be induced by both physiological stimuli and cytotoxic treatment with many anticancer agents. This digestion has generally been considered to be mediated by a Ca2+/Mg(2+)-dependent endonuclease that is activated by increases in intracellular Ca2+. However, we suggest that an alternate endonuclease, DNase II, may be a more likely candidate. In these studies, apoptosis was induced in human HL-60 cells by a 30-min incubation with the topoisomerase II inhibitor etoposide. DNA digestion characteristic of apoptosis began within 3 h of removal of etoposide. Morphological indication of apoptosis was observed concurrently. Only about 20% of the cells underwent apoptosis at this time; these appeared to be cells in S phase at the time of etoposide treatment. The remainder of the cells progressed to the G2 phase and arrested there for at least 48 h. Intracellular Ca2+ and pH were measured in individual cells by flow cytometry. No changes in intracellular Ca2+ were observed, but an acidification of up to 1 pH unit occurred in about 15% of the cells and correlated with the time course of appearance of DNA digestion. Cells were sorted on the basis of intracellular pH and only the acidic cells showed the morphology and DNA digestion characteristic of apoptosis. These results demonstrate the involvement of DNase II in apoptotic DNA digestion and suggest mechanisms of pH homeostasis as regulators of apoptosis.
TL;DR: In this article, the authors explore the link between policy uncertainty and growth and show that the magnitude of policy fluctuation and the persistence of policy jointly determine the pattern of investment and growth.
Abstract: This paper explores links between policy uncertainty and growth. Using an endogenous growth model in which domestic investment is characterized by irreversibilities and policy fluctuates between a high- and a low-tax regime, it shows that the magnitude of policy fluctuation and the persistence of policy jointly determine the pattern of investment and growth. Cross-section regressions confirm that for 46 developing countries over the 1970-85 period, policy uncertainty is negatively correlated with both investment and growth. Policy persistence also plays an important role.
TL;DR: It is concluded that renal collecting duct cells are protected from circulating glucocorticoids by a hitherto undescribed enzyme of the 11-dehydrogenase family, which differs from the known liver enzyme in having a significantly higher affinity for corticosterone and a different cofactor requirement.
Journal Article•
TL;DR: 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, led to normalization of the number of CFU-e derived colonies as well as an increase in theNumber of BFU- e derived colonies, correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.
Abstract: The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (12%) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, > or = 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by > or = 50% from prestudy values); five (12%) improved (> or = 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a > or = 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence.(ABSTRACT TRUNCATED AT 400 WORDS)
TL;DR: In this article, the authors suggest that continental glaciation may have the effect of accelerating biotite weathering, significantly elevating riverine 87Sr/86Sr ratios in regions draining silicate bedrock.
TL;DR: Current clinical research converges on several emerging principles of treatment that address the scope, pace, intensity, and structure of dual-diagnosis programs.
Abstract: Substance abuse is the most common comorbid complication of severe mental illness. Current clinical research converges on several emerging principles of treatment that address the scope, pace, intensity, and structure of dual-diagnosis programs. They include a) assertive outreach to facilitate engagement and participation in substance abuse treatment, b) close monitoring to provide structure and social reinforcement, c) integrating substance abuse and mental health interventions in the same program, d) comprehensive, broad-based services to address other problems of adjustment, e) safe and protective living environments, f) flexibility of clinicians and programs, g) stage-wise treatment to ensure the appropriate timing of interventions, h) a longitudinal perspective that is congruent with the chronicity of dual disorders, and i) optimism.
TL;DR: Until better scientific evidence is available, patients and their physicians cannot make informed choices based on knowledge of the benefits of radical prostatectomy, radiation, or watchful waiting.
Abstract: Objective We performed a structured literature review to define the clinical course of localized prostate cancer, the effectiveness of radical surgery and radiation therapy, and treatment complications. Article selection We identified more than 1600 English-language, MEDLINE referenced articles for 1966 through 1991. All but 144 were excluded because they lacked primary data, involved fewer than 15 patients, or described neither the course of the disease nor treatment complications. Data synthesis In these 144 articles, persistent genitourinary complications were more common after radical surgery than after external-beam radiation. Radiation resulted in a higher incidence of bowel problems. The median annual risks for the development of distant metastases and cancer-related death were 2.6% and 1.0%, respectively. Because tumor grade was correlated with metastases (Spearman correlation r = .56) and cancer mortality (r = .31), controlling for grade was necessary before we could compare the effectiveness of treatments for these outcomes. However, stratification by grade of malignancy was available in only nine of the patient series describing metastatic rates and in seven describing cancer-related mortality. Furthermore, in the patient series that described prostate cancer-related metastatic rates, 48% neglected to identify patients unavailable for follow-up, 92% did not stratify patients by age, and only 48% stratified patients by the extent of disease at treatment. Conclusions Although we were able to compare complications of treatments, we were unable to determine treatment effectiveness for localized prostate cancer because of methodologic inadequacies in the literature we reviewed. Until better scientific evidence is available, patients and their physicians cannot make informed choices based on knowledge of the benefits of radical prostatectomy, radiation, or watchful waiting.