Showing papers by "University of Liverpool published in 1999"
TL;DR: It is shown that Rab5-interacting soluble proteins can completely substitute for cytosol in an in vivo endosome-fusion assay, and that the Rab5 effector EEA1 is the only factor necessary to confer minimal fusion activity.
Abstract: Intracellular membrane docking and fusion requires the interplay between soluble factors and SNAREs. The SNARE hypothesis postulates that pairing between a vesicular v-SNARE and a target membrane z-SNARE is the primary molecular interaction underlying the specificity of vesicle targeting as well as lipid bilayer fusion. This proposal is supported by recent studies using a minimal artificial system. However, several observations demonstrate that SNAREs function at multiple transport steps and can pair promiscuously, questioning the role of SNAREs in conveying vesicle targeting. Moreover, other proteins have been shown to be important in membrane docking or tethering. Therefore, if the minimal machinery is defined as the set of proteins sufficient to reproduce in vitro the fidelity of vesicle targeting, docking and fusion as in vivo, then SNAREs are not sufficient to specify vesicle targeting. Endosome fusion also requires cytosolic factors and is regulated by the small GTPase Rab5. Here we show that Rab5-interacting soluble proteins can completely substitute for cytosol in an in vivo endosome-fusion assay, and that the Rab5 effector EEA1 is the only factor necessary to confer minimal fusion activity. Rab5 and other associated proteins seem to act upstream of EEA1, implying that Rab5 effectors comprise both regulatory molecules and mechanical components of the membrane transport machinery. We further show that EEA1 mediates endosome docking and, together with SNAREs, leads to membrane fusion.
836 citations
TL;DR: This paper discusses the concepts and the development of a methodology to achieve agility based on the emerging paradigm is agile manufacturing, which in concept is a step forward in generation of new means for better performance and success of business.
768 citations
TL;DR: A rating scale using items based on the desired outcomes of shared learning, to assess the `readiness' of health care students for shared learning activities is developed.
Abstract: Objectives:
Although shared learning activities are gradually being introduced to health care undergraduates, it has not been possible to measure the effects of educational interventions on students' attitudes. The main objective of this study was to develop a rating scale using items based on the desired outcomes of shared
learning, to assess the `readiness' of health care students
for shared learning activities.
Design and participants:
A questionnaire study of 120 undergraduate students in 8 health care professions.
Results:
Principal components analysis resulted a 3-factor scale with 19 items and having an internal consistency of 0.9. The factors have been initially named `team-working and collaboration', professional identity' and `professional roles'.
Conclusions:
The new scale may be used to explore differences in students' perception and attitudes towards multi-professional learning. Further work is necessary to validate the scale amongst a larger population.
758 citations
TL;DR: Reading sperm competition and sexual selection is also a way as one of the collective books that gives many advantages.
Abstract: No wonder you activities are, reading will be always needed. It is not only to fulfil the duties that you need to finish in deadline time. Reading will encourage your mind and thoughts. Of course, reading will greatly develop your experiences about everything. Reading sperm competition and sexual selection is also a way as one of the collective books that gives many advantages. The advantages are not only for you, but for the other peoples with those meaningful benefits.
748 citations
TL;DR: In a scanning electron microscope (SEM) an electron beam sets up an omni-directional source of scattered electrons within a specimen, and the backscattered electrons (BSE) will form a diffraction pattern that can be imaged on a phosphor screen.
Abstract: In a scanning electron microscope (SEM) an electron beam sets up an omni-directional source of scattered electrons within a specimen. Diffraction of these electrons will occur simultaneously on all lattice planes in the sample and the backscattered electrons (BSE), which escape from the specimen, will form a diffraction pattern that can be imaged on a phosphor screen. This is the basis of electron backscatter diffraction (EBSD). Similar diffraction effects cause individual grains of different orientations to give different total BSE. SEM images that exploit this effect will show orientation contrast (OC). EBSD and OC imaging are SEM-based crystallographic tools. EBSD enables measurement of the crystallographic orientation of individual rock-forming minerals as small as 1 mu m, and the calculation of misorientation axes and angles between any two data points. OC images enable mapping of all misorientation boundaries in a specimen and thus provide a location map for EBSD analyses. EBSD coupled to OC imaging in the SEM enables complete specimen microtextures and mesotextures to be determined. EBSD and OC imaging can be applied to any mineral at a range of scales and enable us to expand the microstructural approach, so successful in studies of quartz rocks, for example, to the full range of rock-forming minerals. Automated EBSD analysis of rocks remains problematic, although continuing technical developments are enabling progress in this area. EBSD and OC are important new tools for petrologists and petrographers. Present and future applications of EBSD and OC imaging include phase identification, studying deformation mechanisms, constraining dislocation slip systems, empirical quantification of microstructures, studying metamorphic processes, studying magmatic processes, and constraining geochemical microsampling. In all these cases, quantitative crystallographic orientation data enable more rigorous testing of models to explain observed microstructures.
655 citations
TL;DR: A two-factor solution seemed appropriate: depression, tearfulness and wishing to die loaded on the first factor (affective suffering), and loss of interest, poor concentration and lack of enjoyment on the second (motivation).
Abstract: BACKGROUND In an 11-country European collaboration, 14 population-based surveys included 21,724 subjects aged > or = 65 years. Most participating centres used the Geriatric Mental State (GMS), but other measures were also used.
AIMS To derive from these instruments a common depression symptoms scale, the EURO-D, to allow comparison of risk factor profiles between centres.
METHOD Common items were identified from the instruments. Algorithms for fitting items to GMS were derived by observation of item correspondence or expert opinion. The resulting 12-item scale was checked for internal consistency, criterion validity and uniformity of factor-analytic profile.
RESULTS The EURO-D is internally consistent, capturing the essence of its parent instrument. A two-factor solution seemed appropriate: depression, tearfulness and wishing to die loaded on the first factor (affective suffering), and loss of interest, poor concentration and lack of enjoyment on the second (motivation).
CONCLUSIONS The EURO-D scale should permit valid comparison of risk-factor associations between centres, even if between-centre variation remains difficult to attribute.
649 citations
578 citations
TL;DR: Evidence is provided of the current practice of prescribing low-dose oral corticosteroids to all patients with non-acidotic exacerbations of COPD requiring hospital admission and that hospital stays were shorter in the Corticosteroid-treated group.
570 citations
21 Jan 1999-Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment
TL;DR: In this article, a fast and accurate computer simulation program for electron drift and diffusion in gases under the influence of electric and magnetic fields is described and some calculated results are compared to precise experimental results in carbon tetraflouride and methane mixtures.
Abstract: A fast and accurate computer simulation program for electron drift and diffusion in gases under the influence of electric and magnetic fields is described and some calculated results are compared to precise experimental results in carbon tetraflouride and methane mixtures. The calculated Lorentz angles are shown to be typically within 1° of the measured experimental values. The program allows the electric and magnetic fields to be at any angle to each other.
528 citations
Book•
07 Jan 1999TL;DR: The author of this book has been influential in setting the standard for the accurate definition of some of the terms used, and in particular his definition of biocompatibility, agreed at a 1987 conference, has been accepted around the world.
Abstract: There has been a rapid expansion of activity in the field of biomaterials and related medical devices, both in scientific terms and in clinical and commercial applications. The author of this book has been influential in setting the standard for the accurate definition of some of the terms used, and in particular his definition of biocompatibility, agreed at a 1987 conference, has been accepted around the world. The book presents definitions and explanations of 6000 terms used not only in the fields of biomaterials and medical devices, but also in materials science, biological sciences, and clinical medicine and surgery.
478 citations
TL;DR: Proteins in the environment appear to interact with the repassivation process at the surface of these alloys and influence the resulting surface properties.
TL;DR: The modified Ashworth scale is reliable and may assist in studies on the prevalence of spasticity after stroke and the relationship between tone and function and the Tone Assessment Scale is not reliable for measuring posture and associated reactions.
TL;DR: In this article, the authors reviewed estimates of atmospheric inputs to the Mediterranean and some coastal areas, and uncertainities in these estimates considered, and indicated that eolian deposition is an important (50%) or even dominant (>80%) contribution to sediments in the offshore waters of the entire Mediterranean basin.
TL;DR: Despite much conceptual fog lingering over the PBL literature, useful ground rules can be formulated, and this literature review explores what is meant by the term PBL to answer the following questions.
Abstract: Problem-based learning (PBL) has emerged as a useful tool of epistemological reform in higher education, particularly in medical schools. Indeed, PBL has spent most of its career inducing revolutionary undergraduate medical reform. Nevertheless, obtaining informed agreement on the characteristics of the PBL "genus" is a challenge when the label is vulnerable to being borrowed for prestige or subversion. Many "PBL" single-subject courses within traditional curricula do not use PBL at all. Such semantic uncertainty compromises the evidence-base on the added value of problem-based versus traditional approaches and the main messages for good practice. This literature review explores what is meant by the term PBL by aiming to answer the following questions: What difficulties are inherent in the "problem-based" tag? What does the term "problem-based curriculum" imply? How has PBL been characterized and validated by focusing on its purpose? How else has PBL been characterized? How does PBL relate to problem solving? How does PBL relate to epistemological reform? In conclusion, what ground rules can be formulated for PBL? Despite much conceptual fog lingering over the PBL literature, useful ground rules can be formulated.
TL;DR: It is shown that the Ca2-mobilizing molecule nicotinic acid adenine dinucleotide phosphate (NAADP), an endogenous metabolite of β-NADP, triggers a Ca2+ response that varies from short-lastingCa2+ spikes to a complex mixture of short- lasting and long-lasting Ca2+, indicating that NAADP may function as an intracellular messenger in mammalian cells.
Abstract: Many hormones and neurotransmitters evoke Ca2+ release fromintracellular stores, often triggering agonist-specific signatures of intracellular Ca2+ concentration1,2,3,4,5. Inositol trisphosphate (InsP3)1 and cyclic adenosine 5′-diphosphate-ribose (cADPR)6,7 are established Ca2+-mobilizing messengers that activate Ca2+ release through intracellular InsP3 and ryanodine receptors, respectively8,9,10. However, in pancreatic acinar cells, neither messenger can explain the complex pattern of Ca2+ signals triggered by the secretory hormone cholecystokinin (CCK). We show here that the Ca2+-mobilizing molecule nicotinic acid adenine dinucleotide phosphate (NAADP)7,11,12,13,14,15, an endogenous metabolite of β-NADP, triggers a Ca2+ response that varies from short-lasting Ca2+ spikes to a complex mixture of short-lasting (1–2 s) and long-lasting (0.2–1 min) Ca2+ spikes. Cells were significantly more sensitive to NAADP than to either cADPR or InsP3, whereas higher concentrations of NAADP selectively inactivated CCK-evoked Ca2+ signals in pancreatic acinar cells, indicating that NAADP may function as an intracellular messenger in mammalian cells.
TL;DR: The effects of two different types of mitochondrial inhibitor on the cytosolic Ca2+ concentration were tested using simultaneous imaging ofCa2+‐sensitive fluorescence (Fura 2) and electrophysiology and the role played by mitochondria was investigated.
Abstract: Agonist-evoked cytosolic Ca(2+) spikes in mouse pancreatic acinar cells are specifically initiated in the apical secretory pole and are mostly confined to this region. The role played by mitochondria in this process has been investigated. Using the mitochondria-specific fluorescent dyes MitoTracker Green and Rhodamine 123, these organelles appeared as a bright belt concentrated mainly around the secretory granule area. We tested the effects of two different types of mitochondrial inhibitor on the cytosolic Ca(2+) concentration using simultaneous imaging of Ca(2+)-sensitive fluorescence (Fura 2) and electrophysiology. When carbonyl cyanide m-chlorophenylhydrazone (CCCP) was applied in the presence of the Ca(2+)-releasing messenger inositol 1,4, 5-trisphosphate (IP(3)), the local repetitive Ca(2+) responses in the granule area were transformed into a global rise in the cellular Ca(2+) concentration. In the absence of IP(3), CCCP had no effect on the cytosolic Ca(2+) levels. Antimycin and antimycin + oligomycin had the same effect as CCCP. Active mitochondria, strategically placed around the secretory pole, block Ca(2+) diffusion from the primary Ca(2+) release sites in the granule-rich area in the apical pole to the basal part of the cell containing the nucleus. When mitochondrial function is inhibited, this barrier disappears and the Ca(2+) signals spread all over the cytosol.
TL;DR: Patients with somatisation disorders feel satisfied and empowered by medical explanations that are tangible, exculpating, and involving, which could improve these patients' wellbeing and help to reduce the high demands they make on health services.
Abstract: Objectives: To describe, from the perspective of patients, distinguishing features of doctors9 attempts to explain the symptoms of somatisation disorders. Design: Qualitative analysis of verbatim records of interviews in which patients recounted doctors9 explanations of their symptoms. Setting: Patients with persistent somatising symptoms referred from general practices in Liverpool and St Helens and Knowsley were interviewed before entry into a treatment programme. Subjects: 228 of 324 patients referred were interviewed. Initial interviews were used to develop the process and technique, and the final analysis was based on a subsample of 68 records, randomly chosen from the transcripts of 188 subjects who were interviewed subsequently. Results: Doctors9 explanations were often at odds with the patients9 own thinking. Analysis showed that medical explanations could be grouped into one of three categories, defined by the patients9 perceptions. Most explanations were experienced as rejecting the reality of the symptoms. An intermediate category comprised explanations that were viewed as colluding, in which the doctor acquiesced with the patients9 own biomedical theories. However, a few explanations were perceived by patients as tangible, exculpating, and involving. These explanations were experienced by patients as satisfying and empowering. Conclusions: Patients with somatisation disorders feel satisfied and empowered by medical explanations that are tangible, exculpating, and involving. Empowering explanations could improve these patients9 wellbeing and help to reduce the high demands they make on health services.
TL;DR: HNOSCA represents a satisfactory brief outcome measure which could be used routinely in child and adolescent mental health services and was reasonably acceptable to clinicians' from a range of disciplines and services.
Abstract: BACKGROUND Following the development of a child and adolescent version of the Health of the Nation Outcome Scales (HoNOSCA), field trials were conducted to assess their feasibility and acceptability in routine outcome measurement.
AIMS To evaluate the reliability, validity and acceptability of HoNOSCA in routine outcome measurement.
METHOD Following training, 36 field sites provided ratings on 1276 cases at one time point and outcome data on 906. Acceptability was assessed by way of written feedback and at a debriefing meeting.
RESULTS HoNOSCA demonstrated satisfactory reliability and validity characteristics. It was sensitive to change and its ability to measure change accorded with the clinicians' independent rating. HoNOSCA was reasonably acceptable to clinicians' from a range of disciplines and services.
CONCLUSIONS Provided that training needs can be met, HoNOSCA represents a satisfactory brief outcome measure which could be used routinely in child and adolescent mental health services.
TL;DR: In this paper, the authors argue that grooming is a commodity that female primates can trade, either for itself or in exchange for other services (sensu biological markets theory) and that the decision to do either will depend on the degree of competition within a social group.
Abstract: We argue that grooming is a commodity that female primates can trade, either for itself or in exchange for other services (sensu biological markets theory) and that the decision to do either will depend on the degree of competition within a social group. We test this using data from four chacma baboon troops, living in two populations that differ markedly in the degree of contest competition. As predicted by the predominance of grooming dyads in which females are closely ranked there was, in all four troops, a positive correlation between the time invested by one partner and that by the other. In addition, as predicted, the allocation of time was more closely matched in troops where grooming could not be exchanged for anything else. In troops where resource competition was high, we found in one of two troops a positive relationship between rank distance and the discrepancy in time allocation, with the lower ranking of the partners contributing more grooming.
TL;DR: Orexin expression was not obviously related to changes in body weight, insulin, or leptin, but was stimulated under conditions of low plasma glucose in the absence of food, and may participate in the short-term regulation of energy homeostasis by initiating feeding in response to falls in glucose and terminating it after food ingestion.
Abstract: Orexins (hypocretins), novel peptides expressed in specific neurons of the lateral hypothalamic area (LHA), stimulate feeding when injected intracerebroventricularly. We investigated their role in feeding in the rat by measuring hypothalamic prepro-orexin mRNA levels under contrasting conditions of increased hunger. Prepro-orexin mRNA levels increased significantly after 48 h of fasting (by 90-170%; P < 0.05) and after acute (6 h) hypoglycemia when food was withheld (by 90%; P < 0.02). By contrast, levels were unchanged during chronic food restriction, streptozotocin-induced diabetes, hypoglycemia when food was available, voluntary overconsumption of palatable food, or glucoprivation induced by systemic 2-deoxy-D-glucose. Orexin expression was not obviously related to changes in body weight, insulin, or leptin, but was stimulated under conditions of low plasma glucose in the absence of food. Orexins may participate in the short-term regulation of energy homeostasis by initiating feeding in response to falls in glucose and terminating it after food ingestion. The LHA is known to contain neurons that are stimulated by falls in circulating glucose but inhibited by feeding-related signals from the viscera; orexin neurons may correspond to this neuronal population.
TL;DR: In this paper, atmospheric Pb deposition since the Industrial Revolution was studied in western, central, and southern Switzerland using five rural peat bogs, and two distinct periods of Pb enrichment relative to the natural background were found in western and central Switzerland, with enrichments ranging from 40 to 80 times, and between 1960 and 1980 with enrichment values ranging from 80 to 100 times.
Abstract: Atmospheric Pb deposition since the Industrial Revolution was studied in western, central, and southern Switzerland using five rural peat bogs. Similar temporal patterns were found in western and central Switzerland, with two distinct periods of Pb enrichment relative to the natural background: between 1880 and 1920 with enrichments ranging from 40 to 80 times, and between 1960 and 1980 with enrichments ranging from 80 to 100 times. The fluxes also were generally elevated in those time periods: in western Switzerland between 1.16 and 1.55 μg cm-2 y-1 during the first period, and in western and central Switzerland between 0.85 and 1.55 μg cm-2 y-1 during the second period. Between the Industrial Revolution and 1985, nonradiogenic Pb became increasingly important in all five cores because of the replacement of coal by oil after ca. 1920, the use of Australian Pb in industry, and the extensive combustion of leaded gasoline after 1950. The introduction of unleaded gasoline in 1985 had a pronounced effect on...
TL;DR: Fault zone properties are incorporated in production flow simulators using transmissibility multipliers as mentioned in this paper, which are a function of properties of the fault zone and of the grid-blocks to which they are assigned.
Abstract: Fault zone properties are incorporated in production flow simulators using transmissibility multipliers. These are a function of properties of the fault zone and of the grid-blocks to which they are assigned. Consideration of the geological factors influencing the content of fault zones allows construction of high resolution, geologically driven, fault transmissibility models. Median values of fault permeability and thickness are predicted empirically from petrophysical and geometrical details of the reservoir model. A simple analytical up-scaling scheme is used to incorporate the influence of likely small-scale fault zone heterogeneity. Fine-scale numerical modelling indicates that variability in fault zone permeability and thickness should not be considered separately, and that the most diagnostic measure of flow through a heterogeneous fault is the arithmetic average of the permeability to thickness ratio. The flow segregation through heterogeneous faults predicted analytically is closely, but not precisely, matched by numerical results. Identical faults have different equivalent permeabilities which depend, in part, on characteristics of the permeability field in which they are contained.
TL;DR: Agglutination assay results suggest that parasites infecting pregnant women are antigenically distinct from those common in childhood disease and the prevalence of agglutinating antibodies to pregnancy isolates was generally low, but it was highest in multigravidae who are likely to have had the greatest exposure.
Abstract: Plasmodium falciparum malaria during pregnancy is an important cause of maternal and infant morbidity and mortality. Accumulation of large numbers of P. falciparum-infected erythrocytes in the maternal blood spaces of the placenta may be mediated by adhesion of infected erythrocytes to molecules presented on the syncytiotrophoblast surface. In this study, isolates from placentas and peripheral blood of infected pregnant women and from children were tested for binding to purified receptors and for agglutination with adult sera. Results suggest that adhesion to chondroitin sulfate A may be involved in placental parasite sequestration in most cases, but other factors are also likely to be important. Agglutination assay results suggest that parasites infecting pregnant women are antigenically distinct from those common in childhood disease. The prevalence of agglutinating antibodies to pregnancy isolates was generally low, but it was highest in multigravidae who are likely to have had the greatest exposure.
TL;DR: Drug interactions are likely to remain one of the major considerations when selecting a therapeutic regimen for patients with HIV, and the regimen of choice consists of 2 nucleoside analogues plus a protease inhibitor with high in vivo efficacy.
Abstract: There are 3 groups of drugs available for the treatment of patients with HIV disease. These are the nucleoside reverse transcriptase inhibitors ('nucleoside analogues') [zidovudine, didanosine, zalcitabine, lamivudine and abacavir]; the non-nucleoside reverse transcriptase inhibitors (nevirapine, delavirdine and efavirenz); and the protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir and amprenavir). The preferred initial regimen should reduce and maintain plasma HIV RNA below the level of detection. Presently, the regimen of choice consists of 2 nucleoside analogues plus a protease inhibitor with high in vivo efficacy. An alternative combination consists of 2 nucleoside analogues plus a non-nucleoside reverse transcriptase inhibitor. Drug interactions are one of the major problems associated with these multidrug regimens. Changes in plasma concentrations of the nucleoside analogues are unlikely to be of clinical relevance as drug effect is mainly dependent on the rate and extent of intracellular phosphorylation. Combinations of zidovudine plus stavudine, and probably zalcitabine plus lamivudine, should be avoided as competition for phosphorylating enzymes may occur. The antiviral efficacy of some nucleoside analogues, e.g. stavudine, may be compromised by prior treatment with other nucleosides (e.g. zidovudine). However, these data need to be clarified in further studies. It is unlikely that administration of other antiretrovirals will influence the activity of nucleoside analogues. Protease inhibitors are metabolised by hepatic cytochrome P450 (CYP) 3A4. Combination protease inhibitor therapy can result in drug interactions mediated by enzyme inhibition. Ritonavir is the most potent inhibitor, saquinavir the least. The protease inhibitors also interact with the non-nucleoside reverse transcriptase inhibitors. Nevirapine and efavirenz induce drug metabolising enzymes and may reduce plasma concentrations of protease inhibitors. A study in healthy volunteers showed that nelfinavir concentrations are increased by combination with efavirenz. Delavirdine inhibits drug metabolising enzymes and increases the plasma concentration of coadministered protease inhibitors. The nucleoside analogues would not be expected to interact with the protease inhibitors. Apart from the ability of didanosine to reduce the area under the concentration-time curve of delavirdine, there are no reports of clinically significant interactions of other antiretrovirals with the non-nucleoside reverse transcriptase inhibitors. Triple therapy is the current standard of care for patients with HIV disease. However, studies of quadruple therapy are already under way. Drug interactions are likely to remain one of the major considerations when selecting a therapeutic regimen for patients with HIV.
TL;DR: A highly specific, chain length-sensitive fatty acid recognition system exists in the proximal gut mediating CCK secretion and gastric motility and also regulates proximal gastric tone.
TL;DR: This work presents a new framework in which the inconsistencies regarding grooming and relationship negotiation are interpreted in the context of individual decision-making processes and indicates the need for socioecological studies to focus on the dynamics of individual relationships rather than using summary measures.
Abstract: Current socioecological models suggest that the structure of female-bonded primate groups is predicated on the need for coalitionary support in competitive interactions. Social grooming is thought to be the means by which females ensure support from other individuals, either by the direct exchange of grooming for aid or by using grooming as a means of strengthening social bonds. Since these relationships are valuable, they must be regularly serviced and must be repaired if they become damaged. We question this position and show that empirical evidence to support these theoretical arguments is lacking. We then go on to present a new framework in which the inconsistencies regarding grooming and relationship negotiation are interpreted in the context of individual decision-making processes. In this framework, primate groups represent biological markets in which individuals either trade grooming in a reciprocal manner for the direct benefits that grooming itself offers, or exchange it for tolerance by more powerful animals. A number of testable predictions are derived from this hypotheses. The need for socioecological studies to focus on the dynamics of individual relationships rather than using summary measures is emphasized since only a detailed knowledge of serial interaction will provide the key to understanding the complexities of individual decision-making processes.
TL;DR: The Cenomanian-Turonian boundary (CTB) section at Eastbourne, Sussex, England is the thickest at outcrop in the Anglo-Paris Basin, is rich in macro-, micro- and nanno-fossils, and shows less diagenetic alteration than other sections in NW Europe.
TL;DR: Development of at least some human breast cancers is associated with increasing failure to down-regulate ER as cells enter the cycle or to suppress division of ER+ cells, and the mechanism may involve the loss of a tumor suppressor gene.
Abstract: Recently it has been shown that epithelial cell expression of the estrogen receptor (ER) and that of the proliferation-associated marker Ki-67 are almost mutually exclusive in the normal premenopausal human breast but that coexpression frequently occurs in estrogen receptor-positive (ER+) breast cancers. This coexpression may indicate disordered expression of ER in the cell cycle or failure to suppress division of ER+ cells and could be important in neoplastic transformation. The purpose of this study was to determine whether in situ proliferations known to be associated with different levels of risk for developing breast cancer contain these coexpressing cells and, if so, the stage at which they occur. We found that ER+ proliferating cells were rare in premenopausal lobules but increased with age in the normal breast. There was no difference in nonlesional tissue between cancerous and noncancerous breasts. The percentage of dual-expressing cells was significantly increased, however, in all of the in situ proliferations and correlated positively with the level of risk of developing breast cancer. We suggest that development of at least some human breast cancers is associated with increasing failure to down-regulate ER as cells enter the cycle or to suppress division of ER+ cells. The mechanism may involve the loss of a tumor suppresser gene.
TL;DR: Considerable variation occurs in the levels of depression across Europe, the cause for which is not immediately obvious and case and sub-case levels taken together show greater variability, suggesting that it is not a matter of case/sub-case selection criteria, which were standardised by computer.
Abstract: BACKGROUND This is the first report of results from the EURODEP Programme.
AIMS To assess the prevalence of depression judged suitable for intervention in randomised samples of those aged > or = 65 in nine European centres.
METHOD The GMS-AGECAT package.
RESULTS Differences in prevalence are apparent, 8.8% (Iceland) to 236% (Munich). When sub-cases and cases are added together, five high- and four low-scoring centres emerge. Women predominated over men. Proportions of sub-cases to cases revealed striking differences but did not explain prevalence. There was no constant association between prevalence and age. A meta-analysis (n = 13,808) gave an overall prevalence of 12.3%, 14.1% for women and 8.6% for men.
CONCLUSIONS Considerable variation occurs in the levels of depression across Europe, the cause for which is not immediately obvious. Case and sub-case levels taken together show greater variability, suggesting that it is not a matter of case/sub-case selection criteria, which were standardised by computer. Substantial levels of depression are shown but 62-82% of persons had no depressive level. Opportunities for treatment exist.
TL;DR: For patients with lymph node metastasis, extracapsular spread was an important indicator of tumour behaviour and it is recommended its use as a criterion for pathological N staging.